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Biomedical subjects

J B Lewis

Publications and source records attributed to J B Lewis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effect of dental metal ions on glutathione levels in THP-1 human monocytes.

The release of metal ions from dental restorations has been well established, but the sublethal effects of these ions on oral tissues remain undefined. Metal ions are a potential cause of sublethal oxidative stress in cells. Oxidative stress is known to alter cellular processes which are important in the inflammation of tissues. The presence of oxidative stress is commonly assessed by measuring the oxidized (GSSG) and reduced (GSH) forms of cellular glutathione. Normally, the majority of cellular glutathione exists as GSH and the GSH-GSSG ratio is high. Since monocytes often orchestrate inflammatory responses, oxidative stress in monocytes is important. Our hypothesis for the current work was that metal ions induce oxidative stress in monocytes which is manifested by a lower GSH-GSSG ratio. Human THP-1 monocytes were exposed for 24 h to sublethal concentrations of ions of Ag, Be, Co, Cu, Hg, Ni, Pd, and Zn--all known to be released from dental biomaterials. GSH and GSSG were measured using colorimetric assays. Cu lowered the GSH-GSSG ratio as hypothesized, but the ratio could not be determined for other metals because other metal ions interfered with the GSSG assay. However, a statistically significant (ANOVA/Tukey) increase in GSH per cell was observed upon exposure to Ag (50%), Co (100%), Hg (250%) and Zn (10%). This increase may be indicative of an oxidative stress in its own right. Alterations in GSH levels may be important to how released metal ions alter cytokine secretion from monocytes and other cells which play a role in the inflammatory response to dental biomaterials.

Analysis of Variance↗
PubMed2000

4-Hydroxytamoxifen-induced cytotoxicity and bisphenol A: competition for estrogen receptors in human breast cancer cell lines.

Increasing concerns over the effects of environmental estrogens on wildlife and humans have highlighted the need for screening systems to assess potentially estrogenic effects of test compounds. As a result, in vitro screening methods such as cell proliferation assays using the estrogen-responsive human breast cancer cell line, MCF-7, have been developed. The present study describes an alternative in vitro approach for the assessment of such xenoestrogens, based on estrogenic rescue of MCF-7 cells from antiestrogen-induced cytotoxicity. This method measures the ability of various estrogenic compounds to compete with a known estrogen-receptor-mediated antihormonal drug, 4-hydroxytamoxifen, using the 1-[4,5-dimethylthiazol-2-yl]-3,5-diphenylformazan (MTT) assay to assess mitochondrial activity. Because 4-hydroxytamoxifen treatment of cells results in a dramatic decrease in mitochondrial dehydrogenase activity which is directly related to their estrogen-receptor content, inhibition of this effect with estrogenic compounds represents an estrogen-receptor interaction, or estrogenic rescue. The estrogenic compounds tested include a weak xenoestrogen, bisphenol A (BPA), and two biological estrogens, 17alpha- and 17beta-estradiol. Competitive inhibition of 4-hydroxytamoxifen-induced cytotoxicity by BPA was compared to that of the biological estrogens. The results indicate that the biological estrogens can successfully compete with the antiestrogen in a dose-dependent manner. In addition, the assay is sensitive enough to detect estrogenic rescue by even the very weak xenoestrogen, BPA, albeit at high BPA concentrations. This simple in vitro method could be used as an alternative or second-line screen for potential xenoestrogens.

Benzhydryl Compounds↗
PubMed1999

Estrogenicity of bisphenol A and bisphenol A dimethacrylate in vitro.

Although pit and fissure sealants have been utilized extensively in dentistry as a way of preventing occlusal caries, results described by Olea et al. (1996) raised concerns about the safety of sealants and other resin-based dental materials due to the reported presence of bisphenol A (BPA) and its dimethacrylate ester (BPA-DM). Although the release of these compounds from dental materials has not been substantiated by two subsequent studies, we believed it was important to confirm or refute the report that BPA and BPA-DM have estrogenic activity in vitro. We grew breast cancer cells (MCF-7, T-47D, ZR-75-1) known to proliferate under estrogenic stimulation in phenol red-free DMEM containing human serum and concentrations of BPA or BPA-DM ranging from 10(-8)M to 5 x 10(-6)M. After 1 week, plates were harvested for crystal violet or sulforhodamine-B assays, and the optical densities of groups of treated cells were compared with values from control cells. At concentrations at or above 10(-6)M, both BPA and BPA-DM significantly increased cell proliferation (p < 0.05), comparable to the increase seen with 10(-9)M of estrogen. Flow cytometric methods demonstrated that these mitogenic effects occurred within 24 h of exposure to estrogen, BPA, or BPA-DM. The increase in DNA synthesis was analogous to that seen with estrogen stimulation. Thus, we confirmed that BPA and BPA-DM cause cell proliferation at micromolar concentrations that exceed the effective concentrations of estrogen by 1 to 10,000-fold.

Benzhydryl Compounds↗
PubMed1999

A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.

BACKGROUND: Serum creatinine concentration is widely used as an index of renal function, but this concentration is affected by factors other than glomerular filtration rate (GFR). OBJECTIVE: To develop an equation to predict GFR from serum creatinine concentration and other factors. DESIGN: Cross-sectional study of GFR, creatinine clearance, serum creatinine concentration, and demographic and clinical characteristics in patients with chronic renal disease. PATIENTS: 1628 patients enrolled in the baseline period of the Modification of Diet in Renal Disease (MDRD) Study, of whom 1070 were randomly selected as the training sample; the remaining 558 patients constituted the validation sample. METHODS: The prediction equation was developed by stepwise regression applied to the training sample. The equation was then tested and compared with other prediction equations in the validation sample. RESULTS: To simplify prediction of GFR, the equation included only demographic and serum variables. Independent factors associated with a lower GFR included a higher serum creatinine concentration, older age, female sex, nonblack ethnicity, higher serum urea nitrogen levels, and lower serum albumin levels (P < 0.001 for all factors). The multiple regression model explained 90.3% of the variance in the logarithm of GFR in the validation sample. Measured creatinine clearance overestimated GFR by 19%, and creatinine clearance predicted by the Cockcroft-Gault formula overestimated GFR by 16%. After adjustment for this overestimation, the percentage of variance of the logarithm of GFR predicted by measured creatinine clearance or the Cockcroft-Gault formula was 86.6% and 84.2%, respectively. CONCLUSION: The equation developed from the MDRD Study provided a more accurate estimate of GFR in our study group than measured creatinine clearance or other commonly used equations.

Age Factors↗
PubMed1999

Identification and characterization of estrogen-like components in commercial resin-based dental restorative materials.

Recently, resin-based dental restorative materials have been targeted as potential sources of xenoestrogens, specifically bisphenol A (BPA) and bisphenol A dimethacrylate (BAD), which could contribute to overall estrogen load and result in deleterious side effects. The present study used high-pressure liquid chromatography (HPLC) to analyze twenty-eight different commercially available dental resins for the presence of BPA and/or BAD. In addition, sublines of the MCF-7 human breast tumor cell line were cultured in the presence of eluates from eleven of the dental resins and assessed for proliferative responses using the sulforhodamine B assay. Only one resin, Delton II, had detectable levels of BPA or BAD that could be verified by Fourier transform infrared spectrometry. Likewise, eluates from Delton II were the only samples that elicited a significant proliferative response in two of the MCF-7 sublines tested. Therefore, we conclude that dental resins in general do not represent a significant source of BPA or BAD exposure.

Benzhydryl Compounds↗
PubMed1999

In vitro cytotoxicity of resin-containing restorative materials after aging in artificial saliva.

Studies have reported that dental resin-based materials release substances which have biological liabilities. However, some current methods for detecting these substances may not be adequate to detect biologically relevant concentrations. In the current study, we hypothesized that resin-based materials exhibit cytotoxic effects and alter cellular function in vitro when high-pressure liquid chromatography (HPLC-UV detection) cannot detect any release of substances. We further hypothesized that this release continues even after aging the samples in artificial saliva. Five types of composite or compomer materials (Z-100, Tetric Ceram, Dyract AP, Solitaire, and Clearfil AP-X) and one organically modified ceramic material (Definite) were tested after aging in artificial saliva for 0, 7, or 14 days. Cytotoxicity was assessed using direct contact with fibroblasts and measurement of succinic dehydrogenase activity after 48 h of exposure post aging. Release of substances from the materials was assessed using HPLC with UV detection. Altered cellular function was estimated by measuring proliferation of MCF-7 cells with sulforhodamine staining. HPLC showed that whereas initial release of substances was higher without aging, this release dropped significantly after 7 or 14 days of aging, and was equivalent to the Teflon controls after 14 days for four of the materials (Tetric Ceram, Definite, Solitaire, and Clearfil AP-X). Without aging in saliva, all materials had cytotoxicities > 50% of the Teflon negative controls. After 14 days of aging, all materials except the Definite continued to show severe cytotoxicity. Only the Definite could be tested for its ability to alter cellular function because of the continuing toxicity of the other materials. This modified ceramic material caused a significant proliferative effect on the MCF-7 cells indicating that sufficient substances were released to alter cellular function. We concluded that all of these commercially available resin-based dental materials continue to release sufficient components to cause lethal effects or alter cellular function in vitro even after 2 weeks of aging in artificial saliva.

Analysis of Variance↗
PubMed1999

Effect of intensive blood pressure control on the course of type 1 diabetic nephropathy. Collaborative Study Group.

Diabetic nephropathy is the most common cause of end-stage renal disease in the United States. We undertook a study to assess the impact of assignment to different levels of blood pressure control on the course of type 1 diabetic nephropathy in patients receiving angiotensin-converting enzyme (ACE) inhibitor therapy. We also examined the long-term course of this well-characterized cohort of patients receiving ACE inhibitor therapy. One hundred twenty-nine patients with type 1 diabetes and diabetic nephropathy who had previously participated in the Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy Study who had a serum creatinine level less than 4.0 mg/dL were randomly assigned to a mean arterial blood pressure (MAP) goal of 92 mm Hg or less (group I) or 100 to 107 mm Hg (group II). Patients received varying doses of ramipril as the primary therapeutic antihypertensive agent. All patients were followed for a minimum of 2 years. Outcome measures included iothalamate clearance, 24-hour creatinine clearance, creatinine clearance estimated by the Cockcroft and Gault formula, and urinary protein excretion. The average difference in MAP between groups was 6 mm Hg over the 24-month follow-up. The median iothalamate clearance in group I was 62 mL/min/1.73 m(2) at baseline and 54 mL/min/1.73 m(2) at the end of the study compared with a baseline of 64 mL/min/1.73 m(2) and final 58 mL/min/1.73 m(2) in group II. There were no statistically significant differences in the rate of decline in renal function between groups. There was a significant difference in follow-up total urinary protein excretion between group I (535 mg/24 h) and group II (1,723 mg/24 h; P = 0.02). Thirty-two percent of 126 patients achieved a final total protein excretion less than 500 mg/24 h. Patients from groups I and II had equivalent rates of adverse events. In patients with type 1 diabetes mellitus and diabetic nephropathy, the MAP goal should be 92 mm Hg or less for optimal renoprotection, if defined as including decreased proteinuria. With the combination of ACE inhibition and intensive blood pressure control, many patients can achieve regression or apparent remission of clinical evidence of diabetic nephropathy.

Adult↗
PubMed1999

Remission of nephrotic syndrome in type 1 diabetes: long-term follow-up of patients in the Captopril Study.

In 1994, we reported a 3.4 +/- 0.8 year follow-up of the eight patients who experienced remission of nephrotic syndrome during the Collaborative Study Group-sponsored, multicenter trial of captopril therapy in patients with type 1 diabetes with nephropathy (Captopril Study). Of the 409 patients randomized to treatment on the Captopril Study, 108 had nephrotic syndrome (24-hour proteinuria >/= 3.5 g of protein) at baseline. Of these 108 patients, 8 experienced remission of nephrotic syndrome (proteinuria </= 1.0 g/24 h of protein). Remission was significantly associated with captopril therapy and control of systolic blood pressure. The present study describes the status of these eight patients during a follow-up of 7.7 +/- 0.3 years. Since our previous report, one patient has been lost to follow-up and one patient progressed to end-stage renal disease (ESRD) 3.7 years after completion of the Captopril Study. The remaining six patients remain in remission of nephrotic syndrome (mean 24-hour proteinuria, 1.03 +/- 0.3 g of protein) and have stable serum creatinine levels (mean, 1.58 +/- 0.3 mg/dL) and body weights (mean, 69.8 +/- 5.3 kg). Of the six patients, one has discontinued angiotensin-converting enzyme inhibitor (ACEi) therapy because of hypotension. Excluding the patient who progressed to ESRD, the current mean systolic blood pressure is 135 +/- 6 mm Hg and mean diastolic blood pressure is 78 +/- 4 mm Hg. We conclude that long-term remission of nephrotic syndrome and preservation of renal function is achievable in some patients with type 1 diabetes. Control of blood pressure and ACEi therapy appear to be important in achieving long-term remission.

Adult↗
PubMed1998

Impending paradoxical embolism.

The advent of echocardiography has led to the more frequent discovery of impending paradoxical embolism. Paradoxical embolism should be considered whenever there is an arterial embolism from an unidentified source in the presence of a concomitant venous thromboembolic phenomenon. Patients with paradoxical embolism present with neurological abnormalities or features suggesting arterial embolism. Annually, paradoxical embolism may account for up to 47,000 strokes in the United States, and a patent foramen ovale has been reported in up to 35% of the normal population. Events that give rise to pulmonary hypertension may result in a right-to-left shunt through a patent foramen ovale allowing a venous thromboembolism access to the arterial circulation. Herein we report a case of impending paradoxical embolism and review the pertinent literature.

Diagnosis, Differential↗
PubMed1998

Renal pathology patterns in type II diabetes mellitus: relationship with retinopathy. The Collaborative Study Group.

BACKGROUND: The glomerular and retinal vessels are both affected in patients with type I and type II diabetes mellitus. However, the prevalence of the nodular form of diabetic glomerular sclerosis (Kimmelstiel Wilson lesion) and other forms of glomerular pathology including diffuse mesangial sclerosis and their clinical correlates in type II diabetes are less well known. In addition, although recent studies have suggested that non-diabetic glomerular disease was a common cause of proteinuria in type II diabetes, the prevalence of other diseases is unknown. The literature on this subject is clouded by clinical bias regarding patients with diabetes who undergo renal biopsy. METHODS: Glomerular and retinal pathology and clinical correlates were studied in 36 patients enrolled in a prospective clinical trial of patients with type II diabetes mellitus, proteinuria, renal insufficiency, and hypertension. RESULTS: Seventeen biopsies had diabetic glomerular sclerosis with Kimmelstiel Wilson nodules; 15 biopsies had glomerular changes characteristic of the diabetic state including enlarged glomeruli and an increase in mesangial matrix without Kimmelstiel Wilson nodules (mesangial sclerosis lesion); and two had other primary glomerular diseases (IgA and membranous nephropathy). Patients with Kimmelstiel-Wilson nodules had elevated serum creatinines compared to patients with mesangial sclerosis lesions, but there were no other significant differences. Patients with Kimmelstiel Wilson nodules had more severe overall retinopathy than those with mesangial sclerosis lesions (P = 0.0043): six of seven with proliferative retinopathy had Kimmelstiel Wilson nodules, and seven of the eight patients without retinopathy had mesangial sclerosis lesions. CONCLUSIONS: The two discrete patterns of glomerular pathology and the correlation between diabetic retinopathy and the Kimmelstiel-Wilson lesion but not the mesangial sclerosis lesion suggest that the Kimmelstiel Wilson and mesangial sclerosis lesions of diabetic glomerulosclerosis are caused by different pathogenetic mechanisms. In this study, diabetic glomerulosclerosis was responsible for the clinical renal abnormalities in 94%, of patients with type II diabetes mellitus.

Adult↗
PubMed1998

Citrobacter freundii empyema in a patient with occult pulmonary histoplasmosis.

The genus Citrobacter includes three species of organisms that are uncommonly associated with human infection. When they are pathogenic, there are usually one or more associated respiratory, urinary, skin-soft tissue, and central nervous system infections and neonatal sepsis. These infections occur in the wake of significant systemic illness or complicate antibiotic usage. Rarely, infection has been associated with active tuberculosis. The authors report a case of Citrobacter freundii empyema in a patient with occult pulmonary histoplasmosis.

Aged↗
PubMed1997

Structural and antigenic identification of the ORF12 protein (alpha TIF) of equine herpesvirus 1.

The equine herpesvirus 1 (EHV-1) homolog of the herpes simplex virus type 1 (HSV-1) tegument phosphoprotein, alpha TIF (Vmw65; VP16), was identified previously as the product of open reading frame 12 (ORF12) and shown to transactivate immediate early (IE) gene promoters. However, a specific virion protein corresponding to the ORF12 product has not been identified definitively. In the present study the ORF12 protein, designated ETIF, was identified as a 60-kDa virion component on the basis of protein fingerprint analyses in which the limited proteolysis profiles of the major 60-kDa in vitro transcription/ translation product of an ORF12 expression vector (pT7-12) were compared to those of purified virion proteins of similar size. ETIF was localized to the viral tegument in Western blot assays of EHV-1 virions and subvirion fractions using polyclonal antiserum and monoclonal antibodies generated against a glutathione-S-transferase-ETIF fusion protein. Northern and Western blot analyses of EHV-1-infected cell lysates prepared under various metabolic blocks indicated that ORF12 is expressed as a late gene, and cross reaction of polyclonal anti-GST-ETIF with a 63.5-kDa HSV-1 protein species suggested that ETIF and HSV-1 alpha TIF are antigenically related. Last, DNA band shift assays used to assess ETIF-specific complex formation indicated that ETIF participates in an infected cell protein complex with the EHV-1 IE promoter TAATGARAT motif.

Animals↗
PubMed1996

Spontaneous rupture of a vesicourachal diverticulum manifesting as acute abdominal pain.

Urachal abnormalities are rare clinical entities. This article reports a case of a spontaneously ruptured vesicourachal diverticulum manifesting as acute abdominal pain in a healthy 38-year-old man. The embryology, clinical diagnosis, and management of urachal abnormalities are discussed. Emergency physicians should include this clinical entity in their differential diagnoses of patients who develop acute abdominal pain in the absence of trauma, especially when the pain immediately follows a maneuver that increases intra-abdominal pressure.

Abdomen, Acute↗
PubMed1996

Expression and function of the equine herpesvirus 1 virion-associated host shutoff homolog.

The ability of herpes simplex virus types 1 and 2 (HSV-1 and HSV-2, respectively) to repress host cell protein synthesis early in infection has been studied extensively and found to involve the activities of the UL41 gene product, the virion-associated host shutoff (vhs) protein. To date, UL41 homologs have been identified in the genomes of three other alphaherpesviruses: equine herpesvirus 1 (EHV-1), varicella-zoster virus, and pseudorabies virus, but very little is known about the putative products of these homologous genes. Our earlier observations that no rapid early host protein shutoff occurred in EHV-1-infected cells led us to test EHV-1 vhs activity more thoroughly and to examine the expression and function of the EHV-1 UL41 homolog, ORF19. In the present study, the effects of EHV-1 and HSV-1 infections on cellular protein synthesis and mRNA degradation were compared at various multiplicities of infection in several cell types under an actinomycin D block. No virion-associated inhibition of cellular protein synthesis or vhs-induced cellular mRNA degradation was detected in cells infected with any of three EHV-1 strains (Ab4, KyA, and KyD) at multiplicities of infection at which HSV-1 strain F exhibited maximal vhs activity. However, further analyses revealed that (i) the EHV-1 vhs homolog gene, ORF19, was transcribed and translated into a 58-kDa protein in infected cells; (ii) the ORF19 protein was packaged into viral particles in amounts detectable in Western blots (immunoblots) with monoclonal antibodies; (iii) in cotransfection vhs activity assays, transiently-expressed ORF19 protein had intrinsic vhs activity comparable to that of wild-type HSV-1 vhs; and (iv) this intrinsic vhs activity was ablated by in vitro site-directed mutations in which either the functionally inactive HSV-1 vhs1 UL41 mutation (Thr at position 214 replaced by Ile [Thr-214-->Ile]) was recreated within ORF19 or two conserved residues within the putative poly(A) binding region of the ORF19 sequence were altered (Tyr-190, 192-->Phe). From these results we conclude that EHV-1's low vhs activity in infected cells is not a reflection of the ORF19 protein's intrinsic vhs activity but may be due instead to the amount of ORF19 protein associated with viral particles or to modulation of ORF19 protein's intrinsic activity by another viral component(s).

Amino Acid Sequence↗
PubMed1996

Massive rectal bleeding from colonic tuberculosis.

We describe a patient with massive rectal bleeding from colonic tuberculosis. This is an uncommon presentation of gastrointestinal tuberculosis with fewer than 20 cases reported in the medical literature. The incidence of tuberculosis has been increasing during the last decade. The resurgence of tuberculosis (secondary to increased immigration, more patients on immunosuppressive therapy, and the AIDS epidemic) mandates that the clinician be aware of the wide spectrum of presentation of intestinal tuberculosis. Endoscopy is the preferred method used to diagnose colonic tuberculosis.

Acute Disease↗