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J C English

Publications and source records attributed to J C English.

At least 19 recordsLinked to original sources
PubMed2006

Stability of housekeeping genes in alveolar macrophages from COPD patients.

The stability of housekeeping genes is critical when performing gene expression studies. To date, there have been no studies that look at the stability of commonly used housekeeping genes in alveolar macrophages. Expression levels may be affected by culture, stimulation or disease severity. The present study investigated the expression level of 10 housekeeping genes and analysed the stability of their expression in alveolar macrophages from chronic obstructive pulmonary disease patients (n = 22) who were classified according to disease severity. Guanine nucleotide-binding protein, beta polypeptide 2-like 1 (GNB2L1), hypoxanthine phosphoribosyl transferase 1 (HPRT1) and ribosomal protein L32 (RPL32) were the most stably expressed in alveolar macrophages, irrespective of disease severity. There was no difference in the expression levels of 10 housekeeping genes between mild and moderate/severe patients. GNB2L1, HPRT1 and RPL32 were also stably expressed in alveolar macrophages cultured with no stimulation, or with interleukin-1beta, lipopolysaccharide or tumour necrosis factor-alpha stimulation. In conclusion, as fluctuations in the expression of some housekeeping genes were observed, including glyceraldehyde-3-phosphate dehydrogenase, it is recommended that guanine nucleotide binding protein, beta polypeptide 2-like 1 be used as a reference gene for alveolar macrophages in similar study designs, or that the stability of housekeeping genes be validated in alveolar macrophages prior to expression studies.

Aged↗
PubMed2005

Derivation of a human equivalent concentration for n-butanol using a physiologically based pharmacokinetic model for n-butyl acetate and metabolites n-butanol and n-butyric acid.

The metabolic series approach for risk assessment uses a dosimetry-based analysis to develop toxicity information for a group of metabolically linked compounds using pharmacokinetic (PK) data for each compound and toxicity data for the parent compound. The metabolic series approach for n-butyl acetate and its subsequent metabolites, n-butanol and n-butyric acid (the butyl series), was first demonstrated using a provisional physiologically based pharmacokinetic (PBPK) model for the butyl series. The objective of this work was to complete development of the PBPK model for the butyl series. Rats were administered test compounds by iv bolus dose, iv infusion, or by inhalation in a recirculating closed chamber. Hepatic, vascular, and extravascular metabolic constants for metabolism were estimated by fitting the model to the blood time course data from these experiments. The respiratory bioavailability of n-butyl acetate (100% of alveolar ventilation) and n-butanol (50% of alveolar ventilation) was estimated from closed chamber inhalation studies and measured ventilation rates. The resulting butyl series PBPK model successfully reproduces the blood time course of these compounds following iv administration and inhalation exposure to n-butyl acetate and n-butanol in rats and arterial blood n-butanol kinetics following inhalation exposure to n-butanol in humans. These validated inhalation route models can be used to support species and dose-route extrapolations required for risk assessment of butyl series family of compounds. Human equivalent concentrations of 169 ppm and 1066 ppm n-butanol corresponding to the rat n-butyl acetate NOAELs of 500 and 3000 ppm were derived using the models.

1-Butanol↗
PubMed2005

Metabolism and disposition of hydroquinone in Fischer 344 rats after oral or dermal administration.

Studies were conducted to determine the absorption, tissue distribution, excretion, and metabolism of 14C-hydroquinone (HQ) in male and female rats following single oral, repeated oral, or 24-h dermal administration. The concentration of parent compound in blood was also determined following a single 50-mg/kg gavage administration. Absorption into the blood was rapid after oral dosing; the maximum concentration of parent compound was attained within 20 min after dosing, and the maximum concentration of total 14C was attained within 30 min. Parent compound represented 1% of total 14C in blood, indicative of extensive first-pass metabolism. Excretion was primarily via the urine within the first 8h of gavage. Typically, 87-94% of the 14C was excreted in urine. Dermal application of 14C-HQ (20 microCi) as a 5.4% aqueous solution resulted in near background levels of 14C in blood; the maximum mean blood concentration was 0.65 microg HQ equivalents/g in females and not quantifiable in males. The majority (61-71%) of the 14C was recovered from the skin surface by washing at 24 h. HQ was extensively metabolized following oral dosing with typically <3% of the dose excreted as parent compound. The major urinary metabolites of HQ were glucuronide and O-sulfate conjugates, which represented 45-53% and 19-33%, respectively, of an oral dose. A <5% metabolite was identified as a mercapturic acid conjugate of HQ.

Absorption↗
PubMed2001

Localized and systemic scleroderma.

Scleroderma is a broad term encompassing both localized and systemic sclerosis. Localized scleroderma is a cutaneous limited fibrosis that manifests as plaque morphea, generalized morphea, linear scleroderma, and deep morphea. Systemic scleroderma (sclerosis) can manifest as either limited or diffuse disease. Limited systemic sclerosis is typically preceded by Raynaud's phenomenon, involves cutaneous sclerosis distal to the elbows, with gastrointestinal and pulmonary fibrosis, and anticentromere antibody positivity. Diffuse systemic scleroderma is characterized by simultaneous Raynaud's phenomenon, cutaneous skin involvement proximal to the elbow with gastrointestinal, pulmonary, renal and cardiac fibrosis, and positive serology for antitopoisomerase and anti-RNAP III antibodies. This article discusses the classification, epidemiology, pathogenesis, clinical manifestations, treatment, and prognosis of the scleroderma.

Adult↗
PubMed2001

Sarcoidosis.

UNLABELLED: Sarcoidosis is a systemic noncaseating granulomatous disorder of unknown origin. The cutaneous manifestations of sarcoidosis often enable the dermatologist to be the first physician to make the diagnosis. This article reviews essential sarcoidosis pathophysiology, clinical polymorphisms, systemic evaluation, and treatment modalities for cutaneous sarcoidosis to further enhance the dermatologist's understanding of this disease entity. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the theories of the pathogenesis of sarcoidosis, its cutaneous manifestations, its various syndromes and associations, and its presentation in children. Participants should also be more knowledgeable about diagnostic evaluation, measurement of disease progression, treatment modalities, and the prognosis and mortality data of sarcoidosis.

Humans↗
PubMed2000

Development of a physiologically based pharmacokinetic model for hydroquinone.

Hydroquinone (HQ) produces nephrotoxicity and renal tubular adenomas in male F344 rats following 2 years of oral dosing. Female F344 and SD rats are comparatively resistant to these effects. Nephrotoxicity and tumorigenicity have been associated with a minor glutathione conjugation pathway following the oxidation of HQ to benzoquinone (BQ). The majority of administered doses (90-99%) consists of glucuronide and sulfate conjugates of HQ. An initial physiologically based pharmacokinetic model was developed to characterize the role of kinetics in the strain differences observed in HQ-induced renal toxicity and tumorigenicity. Partition coefficients, protein-binding, and metabolic rate constants were determined directly or estimated from a series of in vivo and in vitro studies. Metabolism was confined to the liver and GI tract. The total flux through the glutathione pathway represented the "internal dose" of HQ for nephrotoxicity. Simulations were compared to a variety of data from male and female F344 rats, male SD rats, and a single male human volunteer. Simulations of intraperitoneal administration resulted in higher amounts of glutathione conjugates than comparable oral doses. This was consistent with protein-binding and toxicity studies and emphasized the importance of first-pass GI tract metabolism. In addition, male F344 rats were predicted to form more total glutathione conjugates than SD rats at equivalent dose levels, which was also consistent with the observed strain differences in renal toxicity. This model represents the first stage in the development of a biologically based dose-response model for improving the scientific basis for human health risk assessments of HQ.

Adult↗
PubMed2000

Covalent protein adducts of hydroquinone in tissues from rats: identification and quantitation of sulfhydryl-bound forms.

The Michael-type addition of sulfhydryl groups to benzoquinone (BQ) or substituted benzoquinones is proposed as the primary mechanism by which these electrophilic intermediates react with either cellular glutathione or protein sulfhydryls. This reaction constitutes a reductive alkylation with a substituted hydroquinone (HQ) derivative resulting from the addition. In the case of HQ, oxidative conversion of the parent material to BQ followed by conjugation with glutathione leads to metabolic activation, producing intermediates which are nephrotoxic as well as having other proposed biological activities. Chemically, BQ may react with more than 1 equiv of glutathione (or other sulfhydryl reagents) to produce HQ derivatives substituted with up to four sulfhydryl groups. Similarly, multiply substituted protein-S adducts of HQ were anticipated to occur in vivo following administration of this material. In the current studies, sulfhydryl-bound HQ protein adducts were detected and quantitated in protein isolated from rats using a modification of the alkaline permethylation procedure of Slaughter and Hanzlik [(1993) Anal. Biochem. 208, 288-295]. In particular, total protein-S adducts to HQ in kidney or blood reached a level of 420 or 80 pmol/mg of protein, respectively, 6 h following a single gavage dose of 100 mg/kg HQ. Measured half-lives of protein-S adducts in kidney and blood were 23.9 and 36.0 h, respectively. The applicability of protein-S adducts as a tissue dosimeter for HQ is discussed.

Animals↗
PubMed2000

Covalent protein adducts of hydroquinone in tissues from rats: quantitation of sulfhydryl-bound forms following single gavage or intraperitoneal administration or repetitive gavage administration.

The current studies were conducted to investigate the degree and type of protein binding of hydroquinone (HQ) in the rat following single oral or intraperitoneal (ip) or repeated oral administrations. Male or female F-344 rats or male SD rats received a single dose of HQ at 0, 25, 50, or 100 mg/kg by either gavage or ip injection (SD rats only). In addition, male or female F-344 or male SD rats received HQ by gavage for 6 weeks (5 days/week) at 0, 25, or 50 mg/kg/day. Sulfhydryl-bound HQ was quantitated in protein from blood, kidneys, livers, or spleens 24 h after treatment using an alkaline permethylation procedure. The amount of total protein-S adducts increased with increasing dose in all the tissues that were assayed. Female rats had higher levels of adducts in blood, livers, and kidneys than did male rats when they were treated orally. Male F-344 rats treated orally had elevated levels of adducts in these same tissues compared to SD rats treated orally. For all genders and strains of rats and for all treatment regimens, mono-adducts predominated in livers (>72% of total). In the kidneys, tri- and tetrasubstituted adducts predominated with the summation accounting for >60% of the total. Ip administration of HQ resulted in significantly elevated levels of adducts in all the tissues that were examined, with the greatest increases seen for protein from blood and spleens. Levels of protein-S adducts of HQ in rat kidney following a single gavage administration correlated well with previously published differences in acute HQ nephrotoxicity in rats (female F-344 rat > male F-344 rat > male SD rat). Elevated levels of HQ protein-S adducts following repeated gavage administration did not correlate to measurable clinical signs of nephrotoxicity. Evidence is presented suggesting a possible role for the prostaglandin H synthase complex in the metabolic activation of HQ. In addition, protein arylation alone cannot account for the greater sensitivity of male F-344 rats toward chronic administration of HQ. The sensitivity of male F-344 rats to HQ is likely due to other factors, including the incidence and severity of chronic progressive nephropathy.

Administration, Oral↗
PubMed2000

Lack of induction of micronuclei in human peripheral blood lymphocytes treated with hydroquinone.

Hydroquinone (HQ) has been reported to produce chromosomal effects in some in vivo and in vitro animal models. Its potential for inducing similar effects in human lymphocytes is less clear. The purpose of this study was to examine human lymphocytes treated with HQ for the presence of chromosomal anomalies, using an accepted assay for micronuclei. In addition, the stability of HQ in culture medium was determined to verify exposures. Lymphocyte cultures were obtained from eight donors so that variable responses amongst individuals could be assessed. The micronucleus assays utilized were a common 72 h assay with no wash, as well as two assay variations to maximize cell division. Assay variations consisted of either cell washing at 44 h or allowing unwashed cultures an extra 24 h recovery period before harvest. In all assays treatment was at 24 h post-mitogenic stimulation and cytochalasin B was added to stop dividing cells from undergoing cytokinesis. Thus, cells that were scored had undergone one division in the presence of the chemical. Stability results showed that while HQ was detectable in cultures at least for 15 h, it was considerably more stable at 25 than at 100 or 250 microM treatment levels. Results generated using any of the three micronucleus assay variations showed no significant increase in micronuclei in cultures treated with 12.5-200 microM HQ. Colchicine, the positive control and a known spindle disrupter, produced elevated levels of micronuclei. At certain HQ concentrations, a block in cell division was observed, as evidenced by a decrease in percent binucleated cells and replicative index end-points. By varying the assay conditions, cell cultures overcame this block in division and divided at HQ concentrations up to 200 microM, depending on the donor. The reversible block in cell division observed may be a protective response, allowing cells to recover without gross chromosomal damage. This study has substantially expanded the database with regard to the effects of HQ treatment on lymphocytes.

Adolescent↗
PubMed2000

Family approach for estimating reference concentrations/doses for series of related organic chemicals.

The family approach for related compounds can be used to evaluate hazard and estimate reference concentrations/doses using internal dose metrics for a group (family) of metabolically related compounds. This approach is based upon a simple four-step framework for organizing and evaluating toxicity data: 1) exposure, 2) tissue dosimetry, 3) mode of action, and 4) response. Expansion of the traditional exposure-response analysis has been increasingly incorporated into regulatory guidance for chemical risk assessment. The family approach represents an advancement in the planning and use of toxicity testing that is intended to facilitate the maximal use of toxicity data. The result is a methodology that makes toxicity testing and the development of acceptable exposure limits as efficient and effective as possible. An example is provided using butyl acetate and its metabolites (butanol, butyraldehyde, and butyrate), widely used chemicals produced synthetically by the industrial oxo process. A template pharmacokinetic model has been developed that comprises submodels for each compound linked in series. This preliminary model is being used to coordinately plan toxicity studies, pharmacokinetic studies, and analyses to obtain reference concentrations/doses. Implementation of the family approach using pharmacokinetic modeling to obtain tissue dose metrics is described and its applications are evaluated.

Acetates↗
PubMed2000

Presternal bronchogenic sinus with predunculated lymphoid aggregate.

Congenital cranial, cervical, and upper thoracic sinuses are rare conditions that historically have been classified according to their location and/or pathology. However, published reports of bronchogenic or branchial anomalies are on the increase, and the traditional defining characteristics--location and histopathology--are proving to be less reliable. We describe the pathologic and clinical findings of a congenital presternal pedunculated lesion with a sinus, and review the literature to describe its proper classification.

Adult↗
PubMed2000

Gingival lesions and nasal obstruction in an immunosuppressed patient post-liver transplantation.

Although rare, metastatic hepatocellular carcinoma (HCC) presenting only to the mandible, gingiva, and nasal cavity in patients subsequently found to have primary HCC has been reported. In the age of transplantation, certain HCC patients may receive treatment with an orthotopic liver transplant. Due to the proclivity of HCC for early micrometastases, immunosuppressive therapy can induce significant metastatic lesions. Nasal mass obstruction, gingival lesions, or facial growths in this population must be considered metastatic until proven otherwise.

Adult↗
PubMed2000

Therapeutic potential of platelet-activating factor antagonism in the management of myocardial infarction.

BACKGROUND: Antagonists of platelet-activating factor (PAF) reduce myocardial postischemia reperfusion injury when given before the onset of ischemia. However, the effects of PAF antagonists when administered at a clinically modelled time (during ischemia but before reperfusion) are controversial. Moreover, the extended survival (eight day) and the characteristics of scar formation after treatment with PAF antagonists have not been investigated. OBJECTIVES: To determine the therapeutic potential of PAF antagonist TCV-309 for the treatment of regional myocardial ischemia-reperfusion injury; and to determine the effects of TCV-309 on cardiovascular recovery, evolution of scar formation and survival eight days after a myocardial infarction treated with reperfusion. ANIMALS AND METHODS: Swine underwent regional myocardial ischemia for 60 mins by ligation of the left anterior descending coronary artery, followed by reperfusion for eight days. The treated group (n=7) received PAF antagonist TCV-309 (0.1 mg/kg) 45 mins after ligation; the untreated group (n=7) received vehicle only. RESULTS: Untreated animals experienced significantly (P<0.001) lower systemic arterial blood pressure during the reperfusion period than animals treated with TCV-309. Furthermore, untreated animals required significantly more (P<0.01) antiarrhythmic and inotropic support. Only two of seven animals in the untreated group survived, which was significantly different (P<0.05) from the six of seven treated animals that survived for eight days. Morphometric analyses did not show differences between groups in the characteristics of scar formation following reperfusion for eight days. CONCLUSIONS: PAF antagonist TCV-309 improves survival and reduces cardiovascular dysfunctions associated with regional myocardial ischemia reperfusion injury when administered at a clinically modelled time.

Animals↗
PubMed2000

Sporadic congenital leukonychia with partial phenotype expression.

GOAL: To describe the characteristics and inheritance pattern of a case of congenital leukonychia. OBJECTIVES: 1. To describe the etiologies of congenital and acquired leukonychia. 2. To discuss the differential diagnosis of leukonychia. 3. To outline inheritance patterns associated with leukonychia.

Child↗