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J Harrison

Publications and source records attributed to J Harrison.

At least 19 recordsLinked to original sources
PubMed1992

Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite.

Superoxide dismutase and Fe3+EDTA catalyzed the nitration by peroxynitrite (ONOO-) of a wide range of phenolics including tyrosine in proteins. Nitration was not mediated by a free radical mechanism because hydroxyl radical scavengers did not reduce either superoxide dismutase or Fe3+EDTA-catalyzed nitration and nitrogen dioxide was not a significant product from either catalyst. Rather, metal ions appear to catalyze the heterolytic cleavage of peroxynitrite to form a nitronium-like species (NO2+). The calculated energy for separating peroxynitrous acid into hydroxide ion and nitronium ion is 13 kcal.mol-1 at pH 7.0. Fe3+EDTA catalyzed nitration with an activation energy of 12 kcal.mol-1 at a rate of 5700 M-1.s-1 at 37 degrees C and pH 7.5. The reaction rate of peroxynitrite with bovine Cu,Zn superoxide dismutase was 10(5) M-1.s-1 at low superoxide dismutase concentrations, but the rate of nitration became independent of superoxide dismutase concentration above 10 microM with only 9% of added peroxynitrite yielding nitrophenol. We propose that peroxynitrite anion is more stable in the cis conformation, whereas only a higher energy species in the trans conformation can fit in the active site of Cu,Zn superoxide dismutase. At high superoxide dismutase concentrations, phenolic nitration may be limited by the rate of isomerization from the cis to trans conformations of peroxynitrite as well as by competing pathways for peroxynitrite decomposition. In contrast, Fe3+EDTA appears to react directly with the cis anion, resulting in greater nitration yields.

Animals↗
PubMed1992

Defining and predicting tracheoesophageal puncture success.

There is considerable variability in the reported success rates of tracheoesophageal puncture due, in part, to the lack of a clear definition of success and a paucity of knowledge about factors that determine success. In this article, we define success on a continuum with the use of a 15-point rating scale that incorporates aspects of use and quality of speech and ability to care for the fistula and prosthesis. We suggest a cutoff score for functional and nonfunctional speakers. We define immediate and short- and long-term success. Variables related to the patient, clinician, surgical procedure, and extent of disease were subjected to a multiple regression analysis to determine which predicted success. Overall success was predicted by greater clinician expertise, younger patient age, and better patient health. We discuss the use of the rating scale and an equation to predict success.

Adult↗
PubMed1992

Phase II trial of 5-fluorouracil, high-dose leucovorin calcium, and dipyridamole in advanced prostate cancer.

To examine the effect of altering intracellular folate pools on the efficacy of 5-fluorouracil (FUra) in the treatment of advanced prostate cancer, we performed a phase II trial of FUra (300-370 mg m-2 day-1 x 5 as an i.v. bolus) combined with high-dose folinic acid (500 mg m-2 day-1 x 5.5 days by continuous i.v. infusion) and dipyridamole (75 mg p.o. every 6 h x 5.5 days) administered on a 28-day schedule in patients with stage D2 disease. A group of 13 patients have been treated. The median age was 68 years (range 48-78 years); the performance status ranged from 50% to 90%. Among 12 evaluable patients, there were no objective responders; the median time to progression was 1.9 months. Median survival after entry on this trial was 8.6 months. Treatment with FUra, high-dose folinic acid and dipyridamole was well tolerated. Only one episode each of grade 3 leukopenia, granulocytopenia, and thrombocytopenia was observed. These results suggest that, despite previous trials demonstrating activity for FUra in stage D2 prostate cancer, this disease may be relatively resistant to fluoropyrimidines and, thus, less amenable to biochemical modulation with high-dose folinic acid and dipyridamole.

Aged↗
PubMed1992

An investigation of the relationship between microbial and particulate indoor air pollution and the sick building syndrome.

The sick building syndrome has been the subject of research for approximately 10 years. Although it is often suggested that symptoms in office workers are due to circulating micro-organisms or particles, epidemiological studies investigating the relationship between them have been lacking. This cross-sectional study has combined medical and aerobiological assessments of offices in Great Britain and has found that, although airborne particulates and micro-organisms are unlikely to be the sole cause of the sick building syndrome, positive associations between symptom prevalence rates and levels of airborne viable bacteria and fungi within groups of buildings with similar ventilation systems, suggest a possible causal link that should be explored.

Air Microbiology↗
PubMed1992

Measurement of crosslinked fibrin derivatives in patients undergoing abdominal surgery: use in the diagnosis of postoperative venous thrombosis.

Levels of plasma crosslinked fibrin derivatives, a sensitive and direct marker of the lysis of intravascular crosslinked fibrin, were measured serially in 135 patients undergoing major abdominal surgery to determine their behavior and their use as a screening test for postoperative venous thrombosis. Preoperative levels and levels on the first postoperative day were significantly higher by both enzyme immunoassay and latex assay in 31 patients who developed venous thrombosis (positive venography) than in 104 patients who did not (negative 125I fibrinogen leg scan). Preoperative XLFDP levels 400 ng/ml (enzyme immunoassay) had a sensitivity to the diagnosis of postoperative venous thrombosis of 58%, specificity 74%, positive predictive value 41% and negative predictive value of 85%. The sensitivity of XLFDP levels over 1200 ng/ml on the first postoperative day was 65%, specificity 73%, positive predictive value 38% and negative predictive value 89%. These cutoff values were chosen (high negative predictive value) to allow identification of patients who were unlikely to have venous thrombosis. Measurement of plasma XLFDP, a simple inexpensive test, could be used as a screen to select patients for surveillance procedures (IPG or duplex ultrasonography). A substantial increase in XLFDP levels (greater than 500 ng/ml) occurred in virtually all patients, suggesting that fibrinolysis is not 'shutdown' postoperatively and that these assays reflect lytic activity at the fibrin surface more accurately than do measurements of plasminogen activators and their inhibitors.

Abdomen↗
PubMed1992

The effects of an oral thromboxane TP receptor antagonist BAY u 3405, on prostaglandin D2- and histamine-induced bronchoconstriction in asthma, and relationship to plasma drug concentrations.

1. The potent bronchoconstrictors prostaglandin (PG) D2, PG F2 alpha and thromboxane A2 are thought to have a role in the pathogenesis of asthma, mediated via the thromboxane (TP) receptor. 2. BAY u 3405 is a new potent selective competitive TP receptor antagonist. 3. The effect of single oral doses of 20 mg and 50 mg BAY u 3405 was examined against histamine and PG D2 bronchial provocation at 90 min after drug ingestion and, for the 20 mg dose alone, at 60 min after ingestion, in randomised, double-blind placebo controlled crossover studies. A time course study was performed with the 20 mg dose. 4. BAY u 3405 protected against PG D2 bronchial provocation. The 20 mg dose increased the amount of PG D2 required to produce a fall of 20% in the forced expiratory volume in 1 s by 6-fold and 16-fold at 60 min and 90 min after ingestion respectively, and the 50 mg dose by 14-fold at 90 min after ingestion. 5. The specificity of the drug was confirmed in vivo in that there was no significant protection against histamine bronchial provocation at either dose or at either time point. 6. The time course study showed significant protection against PG D2 bronchial provocation at 1 h and at 3 h after a single 20 mg oral dose. 7. There was no correlation between subjects in plasma BAY u 3405 concentration and drug effect. Within the subjects performing the time course study there was a strong correlation in time between drug effect and plasma BAY u 3405 concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Hypertension, coronary artery disease and insulin resistance--linked disorders with an impact on treatment.

Coronary artery disease is a very common disorder for which hypertension is a well-recognized risk factor. However many trials of antihypertensive therapy have failed to demonstrate a reduction in the incidence of coronary events. One explanation is that hypertension is a disorder associated with hyperinsulinaemia, obesity and non-insulin dependent diabetes. Furthermore certain antihypertensive drugs, notably thiazide diuretics, increase the hyperinsulinaemia and thereby increase one of the other coronary risk factors. In this review the links between hypertension and hyperinsulinaemia are explored and the mechanisms whereby an increased plasma insulin can lead to the more rapid development of coronary artery disease are explained. These observations may influence the choice of drugs used to treat hypertension.

Arteriosclerosis↗
PubMed1992

An arthroconidial-spherule antigen of Coccidioides immitis: differential expression during in vitro fungal development and evidence for humoral response in humans after infection or vaccination.

A 33-kDa protein antigen purified from spherules of Coccidioides immitis was analyzed for ultrastructural localization and for binding to serum antibodies from infected or immunized humans. By using colloidal gold detection of affinity-purified anti-33-kDa protein antibodies, electron photomicrographs showed binding to the inner cell wall of arthroconidia and spherules and to the septa and glycocalyx surrounding endospores. Enzyme immunoassay measurements also demonstrated that the antigen was most abundant in mature spherules. Of 37 patients with coccidioidomycosis but without concurrent human immunodeficiency virus infections, all but 2 demonstrated immunoglobulin M (IgM) (usually with early infection) or IgG antibodies for the 33-kDa antigen. In contrast, only one of four HIV-infected patients with active coccidioidal infections demonstrated antibody. On the other hand, 107 of 108 patients without evident coccidioidomycosis and 15 of 16 patients with histoplasmosis did not have similar antibodies, indicating a high degree of specificity. Immunization of humans with a spherule vaccine produced IgM responses to this antigen that were not evident in placebo recipients.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Mutational inactivation of an inhibitory sequence in human immunodeficiency virus type 1 results in Rev-independent gag expression.

We have characterized an inhibitory RNA element in the human immunodeficiency virus type 1 (HIV-1) gag coding sequence that prevents gag expression. The inhibition exerted by this element could be overcome by the presence of the Rev-responsive element in cis and of Rev protein in trans. To understand the mechanism of function, we inactivated the inhibitory element by mutagenesis while maintaining an intact gag coding region. A constitutive high level of Rev-independent gag expression was achieved only after the introduction of 28 point mutations over a large region of 270 nucleotides within the gag coding region. To our knowledge, this is the first demonstration of inactivation of a negative RNA element within a coding region without alteration of the expressed protein. Elimination of the inhibitory element in the p17gag region, named INS-1, offered the opportunity to detect a second inhibitory element in the gag-pol region. The presence of either INS element is sufficient to inhibit gag expression, demonstrating that multiple INS elements acting independently can inhibit HIV RNA expression. Expression of gag from Rous sarcoma virus, a retrovirus that does not require Rev-like regulatory proteins, revealed that the Rous sarcoma virus p19gag region does not contain inhibitory elements. These results demonstrate the presence of a strong inhibitory element acting at the level of mRNA and provide a general method for the removal of such elements from mRNA coding regions. The inhibitory element functions in the absence of any HIV-1 proteins, suggesting that cellular factors are responsible for this inhibition.

Base Sequence↗
PubMed1992

Variability in response to a low-fat, low-cholesterol diet in children with elevated low-density lipoprotein cholesterol levels.

The reduction of dietary cholesterol and fat lowers low-density lipoprotein cholesterol (LDL-C) and reduces risk of coronary heart disease in adults. The purpose of this study was to determine the individual variability of response of serum lipid and lipoprotein levels to a low-fat, low-cholesterol diet in children with elevated LDL-C levels. Thirty-two children (2 to 16 years of age) enrolled in a diet modification program, who had LDL-C levels of at least 110 mg/dL but normal triglyceride levels for their ages, were studied. Lipid levels and dietary nutrients were analyzed at the time of admission, and final assessments were made at least 3 months after entry. There was a significant correlation, for the group as a whole, between change in LDL-C concentration and change in grams of dietary saturated fat; however, there was marked individual variability in LDL-C response. There were no significant correlations between changes in LDL-C levels and changes in either total fat, polyunsaturated fat, or cholesterol intake. It is concluded that modest decreases in dietary saturated fat coincide with a lowering of LDL-C concentration, over a short term, in many children, but the degree of lowering varies considerably from one child to another. This variability is consistent with the concept that response of serum lipid levels to dietary changes is modified by genetic, metabolic, and other, as of yet, undefined variables.

Child↗
PubMed1992

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Death↗
PubMed1991

DNA binding, adduct characterisation and metabolic activation of aflatoxin B1 catalysed by isolated rat liver parenchymal, Kupffer and endothelial cells.

In vitro studies with rat liver parenchymal, Kupffer and endothelial cells isolated from male Sprague-Dawley rats were undertaken to investigate cell-specific bioactivation of aflatoxin B1, DNA binding and adduct formation. In the mutagenicity studies, using homogenates of all three separated liver cell populations (co-incubated with NADP+ and glucose-6-phosphate as cofactors for the cytochrome P-450 monooxygenase system) parenchymal, Kupffer and endothelial cells were able to activate aflatoxin B1 to a metabolite mutagenic to Salmonella typhimurium TA 98. In the case of nonparenchymal cells (i.e. Kupffer and endothelial cells) 10-fold higher concentrations of aflatoxin B1 had to be used to obtain a similar number of revertants to that observed with parenchymal cells. Induction studies with Aroclor 1254 led to a striking decrease in the activation of aflatoxin B1 in parenchymal cells, whereas nonparenchymal cells had a slightly enhanced metabolic activation capacity for aflatoxin B1. Metabolism studies with microsomes from induced and noninduced cells using testosterone as substrate revealed comparable results: after induction with Aroclor 1254, parenchymal cells showed a 60% decrease in the formation rate of 2 alpha-hydroxytestosterone, whereas the formation rate of this metabolite remained unchanged in nonparenchymal cells; 2 alpha-hydroxytestosterone is specifically formed by cytochrome P-450 IIC11, which also catalyses the activation of aflatoxin B1 to its epoxide. When freshly isolated, intact cells were incubated with tritiated aflatoxin B1, a dose-dependent aflatoxin B1 binding to DNA in parenchymal and nonparenchymal cells was observed. HPLC analysis of DNA acid hydrolysates of all three cell types showed the major adduct to be 8,9-dihydro-8-(N7-guanyl)-9-hydroxy-aflatoxin B1.

Aflatoxin B1↗
PubMed1991

Angioblast differentiation and morphogenesis of the vascular endothelium in the mouse embryo.

Bandeiraea simplicifolia B4 isolectin (BSLB4) and polyclonal antisera against von Willebrand factor (VWF) were used to study the origin of endothelial cells and their organization into blood vessels in the postimplantation mouse embryo. Examination of BSLB4-stained whole mounted and sectioned embryos revealed intense staining of the endothelium, highlighting large vessels, capillaries, and many individual cells. Dorsal aorta formation was first obvious at E7 when many lectin-positive cells appeared in paraxial and lateral plate mesoderm. As development proceeded to E8, BSLB4-positive cells became organized into craniocaudal lines destined to become the aorta proper. At E9, BSLB4 stained all vessels of the embryo including the dorsal aorta, the intersomitic arteries, and the endocardium. VWF expression was not detected until E8 when BSLB4/VWF double-stained sections revealed the dorsal aortae as the first VWF-positive vessels, while other endothelium visible with BSLB4 remained negative for VWF immunostaining. By E12 many other vessels became VWF-positive, including the aortic arches, the intersomitic arteries, and the cardinal veins. However, many angioblasts and capillaries remained VWF-negative, reflecting the heterogeneous expression of VWF among endothelium that has been reported in adults of other species. The histochemical data reported here support the conclusions of earlier avian studies by showing distinct vascular patterns in the initial formation of vessels from isolated angioblasts (vasculogenesis), followed by the extension and organization of the initial vascular structures (angiogenesis). Moreover, our data suggest that the endothelium arises from distinct VWF-positive sources associated with the dorsal aorta, as well as VWF-negative sources associated with other vessels in the embryo.

Animals↗
PubMed1991

An immunoreactive apoglycoprotein purified from Coccidioides immitis.

Deglycosylation of glycoproteins in a lysate of spherules of Coccidioides immitis has permitted purification and partial characterization of a proline-rich pronase-sensitive antigen. Moreover, soluble antigen specifically stimulated lymphocytes from persons with dermal delayed-type hypersensitivity to coccidioidal antigens. When related to reference coccidioidin by tandem two-dimensional immunoelectrophoresis, the antigen fused in the anodal region with a specific reference antigen (antigen 2). It did not show identity with coccidioidal antigens used in conventional serologic assays. Although immunoblots of the purified protein with monospecific rabbit antiserum showed a single antigen at 33 kDa, the parent spherule lysate bound the same antibody in a broad band between 70 and greater than 200 kDa, which could be explained by microheterogeneity of glycosylation. Immunoelectron microscopy using affinity-purified human antibodies localized the antigen to the cell wall and internal septa of spherules. These findings suggest that the apoglycoprotein may be important in human immune responses to coccidioidal infection.

Antigens, Fungal↗
PubMed1991

Syphilis treatment response in HIV-infected individuals.

The adequacy of treatment for syphilis has routinely been evaluated by the serological response, i.e. the rapid plasma reagin test (RPR). Since the description of AIDS and HIV aspects of both the natural history of syphilis and the response of Treponema pallidum to treatment have come under increased scrutiny. With concurrent epidemics of HIV and syphilis in New York City, a serological case-control study was done to determine whether HIV-infected individuals given treatment for primary or secondary syphilis have a modified serological response. All study participants had primary or secondary syphilis and paired specimens available for testing. Cases were defined as people who were HIV-positive and were compared with controls who were HIV-negative. HIV-infected patients with primary syphilis when compared with HIV-negative controls were less likely to have a fourfold or greater RPR decrease or seroreversion within 6 months of treatment [15 out of 28 versus 153 out of 210; odds ratio = 0.4, P less than 0.05]. Cases and controls with secondary syphilis had similar serological responses after treatment for syphilis. Although this study adds to the growing body of literature which suggests that HIV may alter the RPR response, prospective studies are needed to determine definitively whether HIV alters the serological response to therapy in patients with early syphilis.

Adolescent↗
PubMed1990

Clay occlusion of respirable quartz particles detected by low voltage scanning electron microscopy-X-ray analysis.

Respirable-sized dust particles from a clay mine and mill were examined for aluminium and silicon content by scanning electron microscopy-energy dispersive X-ray analysis at incident electron energies of 5-20 keV. Most of the high silica content particles, those which had a silicon to silicon plus aluminium signal fraction, measured at 20 keV, of 0.9 or greater, showed a decrease in the silicon fraction of signal with decreasing incident electron energy, down to values of between 0.6 and 0.8 at 5 keV: this decrease was a function of particle size and composition. Simple models for silicon fraction of signal vs incident electron voltage suggest this behaviour is due to a heterogeneous particle structure in which an aluminosilicate coating occludes the surface of a silica particle core. The coating survives incubation in a major component of pulmonary surfactant.

Aluminum Silicates↗