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Biomedical subjects

J W Davis

Publications and source records attributed to J W Davis.

At least 19 recordsLinked to original sources

Differential DNA methylation patterns of small B-cell lymphoma subclasses with different clinical behavior.

Non-Hodgkin's lymphoma (NHL) is a group of malignancies of the immune system with variable clinical behaviors and diverse molecular features. Despite the progress made in classification of NHLs based on classical methods, molecular classifications are a work in progress. Toward this goal, we used an array-based technique called differential methylation hybridization (DMH) to study small B-cell lymphoma (SBCL) subtypes. A total of 43 genomic DMH experiments were performed. From these results, several statistical methods were used to generate a set of differentially methylated genes for further validation. Methylation of LHX2, POU3F3, HOXC10, NRP2, PRKCE, RAMP, MLLT2, NKX6.1, LRP1B and ARF4 was validated in cell lines and patient samples and demonstrated subtype-related preferential methylation patterns. For LHX2 and LRP1B, bisulfite sequencing, real-time reverse transcriptase-polymerase chain reaction and induction of gene expression following treatment with the demethylating agent, 5'-aza-2'-deoxycytidine, were confirmed. This new epigenetic information is helping to define molecular portraits of distinct subtypes of SBCL that are not recognized by current classification systems and provides valuable potential insights into the biology of these tumors.

Adult↗

The transformation of hexabromocyclododecane in aerobic and anaerobic soils and aquatic sediments.

The biological transformation of hexabromocyclododecane (HBCD), a brominated fire retardant commonly used in a variety of consumer goods, was investigated in aerobic and anaerobic soils and freshwater sediments. Soil, river water, and aquatic sediments were collected from several locations in the United States and transformation of HBCD was evaluated in the correspondingly composed microcosms based on the Organisation for Economic Co-Operation and Development (OECD) Test Guidelines 307 (Aerobic and Anaerobic Transformation in Soil) or 308 (Aerobic and Anaerobic Transformation in Aquatic Sediment Systems). Soil and sediment reaction mixtures, prepared under either aerobic or anoxic conditions, were dosed with HBCD at a concentration ranging from approximately 10 to 80 ng/g dry weight. The soils and sediments were then placed at 20 degrees C for approximately 4 months and the concentration of HBCD in the microcosms was determined at selected time intervals utilizing high-performance liquid chromatography-mass spectrometry (LC-MS). HBCD loss was observed in both the aerobic and anaerobic soils and sediments although the rates were appreciable faster under anoxic conditions. Biologically mediated transformation processes (i.e., biotransformation) accelerated the rate of loss of HBCD when compared to the biologically inhibited (i.e., autoclaved) soils and sediments. Biotransformation half-lives for HBCD were determined to be 63 and 6.9 days in the aerobic and anaerobic soils, respectively, while biotransformation half-lives for HBCD in the two river systems ranged from 11 to 32 days and 1.1 to 1.5 days under aerobic and anaerobic conditions, respectively. Brominated degradation products were not detected in any of the soils or sediments during the course of the study.

Aerobiosis↗

Relating induced in situ conditions of raw chicken breast meat to pinking.

Our objective was to simulate the pink color defect in cooked chicken breast meat with treatment combinations that would induce measurable changes in the conditions of raw meat. In addition, the feasibility of using induced raw meat conditions to develop a logistic regression model for prediction of pinking was studied. Approximately 960 breast fillets from 2 plants with 2 replications were used for inducing in situ conditions with 16 combinations of sodium chloride, sodium tripolyphosphate, sodium erythorbate, and sodium nitrite (present and not present). Muscles in all treatments were subjected to individual injections, followed by tumbling, cooking, and chilling. Raw samples were analyzed for pH, oxidation-reduction potential, and pigment evaluation. Results indicated a significant role of induced in situ conditions of raw meat in the occurrence of pinking. Presence of 1 ppm or more of sodium nitrite in raw meat produced significant pinking of cooked meat. The light muscle color group was least affected and the dark group was most affected by induced pH, oxidation-reduction potential conditions, and metmyoglobin and nitrosopigment content. The predictive ability of the logistic model was more than 90% with nitrosopigment, pH, and reducing conditions being the most important factors. Moreover, validation of the model was confirmed by close association between observed pink samples and those predicted as pink.

Animals↗

Toxoplasma gondii, Neospora caninum, Sarcocystis neurona, and Sarcocystis canis-like infections in marine mammals.

Toxoplasma gondii, Neospora caninum, Sarcocystis neurona, and S. canis are related protozoans that can cause mortality in many species of domestic and wild animals. Recently, T. gondii and S. neurona were recognized to cause encephalitis in marine mammals. As yet, there is no report of natural exposure of N. caninum in marine mammals. In the present study, antibodies to T. gondii and N. caninum were assayed in sera of several species of marine mammals. For T. gondii, sera were diluted 1:25, 1:50, and 1:500 and assayed in the T. gondii modified agglutination test (MAT). Antibodies (MAT > or =1:25) to T. gondii were found in 89 of 115 (77%) dead, and 18 of 30 (60%) apparently healthy sea otters (Enhydra lutris), 51 of 311 (16%) Pacific harbor seals (Phoca vitulina), 19 of 45 (42%) sea lions (Eumetopias jubatus) [corrected] 5 of 32 (16%) ringed seals (Phoca hispida), 4 of 8 (50%) bearded seals (Erignathus barbatus), 1 of 9 (11.1%) spotted seals (Phoca largha), 138 of 141 (98%) Atlantic bottlenose dolphins (Tursiops truncatus), and 3 of 53 (6%) walruses (Odobenus rosmarus). For N. caninum, sera were diluted 1:40, 1:80, 1:160, and 1:320 and examined with the Neospora agglutination test (NAT) using mouse-derived tachyzoites. NAT antibodies were found in 3 of 53 (6%) walruses, 28 of 145 (19%) sea otters, 11 of 311 (3.5%) harbor seals, 1 of 27 (3.7%) sea lions, 4 of 32 (12.5%) ringed seals, 1 of 8 (12.5%) bearded seals, and 43 of 47 (91%) bottlenose dolphins. To our knowledge, this is the first report of N. caninum antibodies in any marine mammal, and the first report of T. gondii antibodies in walruses and in ringed, bearded, spotted, and ribbon seals. Current information on T. gondii-like and Sarcocystis-like infections in marine mammals is reviewed. New cases of clinical S. canis and T. gondii infections are also reported in sea lions, and T. gondii infection in an Antillean manatee (Trichechus manatus manatus).

Agglutination Tests↗

RAPD markers linked to eastern filbert blight resistance in Corylus avellana.

A total of 1,110 decamer primers were screened for RAPD markers linked to a dominant allele in hazelnut ( Corylus avellana) that confers resistance to eastern filbert blight caused by Anisogramma anomala. Twenty RAPD markers linked in coupling, and five markers linked in repulsion, were found. A seedling population was used to construct a linkage map of the region flanking the resistance locus. The map spans 46.6 cM, with 14 markers on one side of the resistance locus and eight on the other side. Eleven markers showed less than 3% recombination with resistance, including three that showed no recombination. Seven of these 11 markers are sufficiently robust to allow their use in marker-assisted selection. These include AA12(850) which shows no recombination, and six markers on one side of the resistance locus: 173(500), 152(800), 122(825), 275(1130), H19(650) and O16(1250). Marker 268(580), which flanks the resistance locus on the other side, is also suitable for use in marker-assisted selection, but shows 5.8% recombination with resistance. Other markers are less suitable for marker-assisted selection because of sensitivity to changes in primer or MgCl(2) concentration, or the long time required for electrophoresis to separate bands of similar size. The 16 markers closest to the resistance locus were cloned and sequenced. The W07(365) marker, which showed no recombination with the resistance locus but is difficult to score, includes a CT microsatellite repeat. The sequence information will allow the design of SCAR primers and eventual map-based cloning of the resistance allele.

Base Sequence↗

[Laparoscopic radical cystectomy with intracorporeal creation of a continent urinary diversion. Future or present?].

Once laparoscopic radical prostatectomy has been mastered, the step to performing a radical cystectomy is not that far. The challenge is to create the urinary diversion by laparoscopy. In this report we describe our experience with 11 laparoscopic radical cystectomies and intracorporeal construction of a continent urinary diversion (Mainz pouch II) as a treatment option in patients with muscle-invading bladder cancer. All 11 procedures could be performed successfully. A conversion to open surgery was not required in any case. The mean surgery time was 6.7 h. Except for two pouch fistulas we did not observe any intra- or postoperative complications. The functional as well as the oncological results are convincing. Less morbidity and faster recovery are the main advantages of this minimally invasive procedure. In addition, the low levels of blood loss, fluid shifts, and electrolyte loss considerably reduce cardiovascular stress. Radical cystectomy and construction of a continent urinary diversion represent the limit of technically feasible laparoscopy and should be done exclusively in specialized centers.

Aged↗

Quantitation of serum prostate-specific membrane antigen by a novel protein biochip immunoassay discriminates benign from malignant prostate disease.

The lack of a sensitive immunoassay for quantitating serum prostate-specific membrane antigen (PSMA) hinders its clinical utility as a diagnostic/prognostic biomarker. An innovative protein biochip immunoassay was used to quantitate and compare serum PSMA levels in healthy men and patients with either benign or malignant prostate disease. PSMA was captured from serum by anti-PSMA antibody bound to ProteinChip arrays, the captured PSMA detected by surface-enhanced laser desorption/ionization mass spectrometry, and quantitated by comparing the mass signal integrals to a standard curve established using purified recombinant PSMA. The average serum PSMA value for prostate cancer (623.1 ng/ml) was significantly different (P < 0.001) from that for benign prostate hyperplasia (117.1 ng/ml) and the normal groups (age <50, 272.9 ng/ml; age >50, 359.4 ng/ml). These initial results suggest that serum PSMA may be a more effective biomarker than prostate-specific antigen for differentiating benign from malignant prostate disease and warrants additional evaluation of the surface-enhanced laser desorption/ionization PSMA immunoassay to determine its diagnostic utility.

Adult↗

Low bone density is not associated with aortic calcification.

The aging process is associated with an increasing prevalence of osteoporosis and aortic calcification, but it is uncertain if these two conditions are interrelated. We examined the relationship between bone mineral density (BMD) and evidence of aortic calcification on spinal radiographs among 524 Japanese-American women living in Hawaii. The prevalence of aortic calcification increased with age from less than 10% below age 55 to essentially all women over age 75. Unadjusted BMD was significantly lower among women with aortic calcification at all measured sites (distal and proximal radius and calcaneus). However, the differences in BMD between women with and without calcification were diminished and no longer significant after adjustment for age. Aortic calcification was positively associated with body mass index (BMI), systolic blood pressure, diabetes, current smoking, and thiazide use, but negatively associated with physical activity index. Multivariate logistic regression analysis showed that age, systolic blood pressure, physical activity index (protective), and current smoking (common etiological factors for aortic calcification) were independently associated with aortic calcification, whereas BMD (mean Z-score) was not. We conclude that there is little evidence to support a direct relationship between osteoporosis (low BMD) and aortic calcification. Osteoporosis and aortic calcification appear to be independent processes that occur as women age. However, potential confounding factors may be involved, and prospective studies are needed to investigate this issue further.

Adult↗

Prevention of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the MCF-10A cell line: correlation with increased transforming growth factor alpha production.

We have recently reported that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits epidermal growth factor (EGF) withdrawal-induced apoptosis in the human mammary epithelial cell line MCF-10A. We hypothesized that TCDD-mediated inhibition of apoptosis was due to its ability to stimulate the EGF receptor (EGFR) pathway. Indeed, in the present studies, the EGFR inhibitor AG1478 was able to prevent TCDD-, EGF-, and transforming growth factor alpha (TGF-alpha)-dependent cell recovery and inhibition of apoptosis. These effects were specific for an EGFR-mediated pathway because cotreatment with AG825, an erbB2 inhibitor, had little effect on apoptosis. In addition, TCDD was able to mimic the EGF and TGF-alpha signaling as demonstrated by increasing Akt and extracellular signal-regulated kinase 1,2 phosphorylation. These effects were dependent on EGFR activity because AG1478, but not AG825, was able to prevent EGF-, TGF-alpha, or TCDD-mediated Akt and extracellular signal-regulated kinase 1,2 phosphorylation. The ability of TCDD to stimulate the EGFR pathway and inhibit apoptosis may be due to the ability of TCDD to increase expression of TGF-alpha, a ligand for EGFR. Treatment with 10 nM TCDD increased TGF-alpha mRNA at 2 h and TGF-alpha protein at 6 h. These data suggest a mechanism whereby TCDD is able to inhibit apoptosis in human mammary epithelial cells by stimulating TGF-alpha production, resulting in an autocrine effect.

Apoptosis↗

The relation between lifestyle factors and biochemical markers of bone turnover among early postmenopausal women.

We examined the associations of two biochemical markers of bone turnover with lifestyle factors in 340 postmenopausal women in Hawaii, ages 45-59 years, from the Early Postmenopausal Intervention Cohort. Physical activity, calcium supplement use, smoking and alcohol use in the prior 2 weeks were measured and examined as independent variables in multiple regression analyses with bone turnover markers as dependent variables, adjusted for weight, height, whole body bone mass, serum estradiol, years since menopause, and ethnicity. Calcium supplement and alcohol use were significantly associated with reduced levels of urinary type I collagen cross-linked N-telopeptides (NTX). The mean NTX level was 12% lower among women using > or = 250 mg of calcium supplements per day as compared with other women, and 20% lower among alcohol users compared with nonusers. Both calcium supplement use and alcohol intake were associated with lower mean serum osteocalcin (a marker of bone formation) and NTX z-scores. By contrast, smoking was associated with lower osteocalcin levels, without any effect on NTX. The osteocalcin level was 12% lower among smokers compared with nonsmokers. In addition, the z-score difference between NTX and osteocalcin was significantly associated with smoking, with a shift towards more NTX than osteocalcin. Physical activity was not significantly associated with either of the markers. These findings suggest that biochemical markers may help to identify lifestyle factors that affect bone, and provide estimates of the relative magnitude of these effects on bone formation and resorption, independent of each other.

Alcohol Drinking↗

Bilateral testicular lymphoma treated with chemotherapy and radiation without orchiectomy: complete response relapsed at 52 months in the vitreous humor.

We report the first detailed case of testicular lymphoma managed with chemotherapy and radiation without orchiectomy. A 60-year-old man with Stage II extralymphatic bilateral testicular lymphoma refused orchiectomy, but underwent cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy and radiation. He remained disease free for 52 months, when a solitary central nervous system relapse to the vitreous humor was diagnosed. The optimal therapy for testicular lymphoma is unclear but often includes orchiectomy with adjuvant chemotherapy and radiation. Stage I testicular lymphoma can be cured by surgery alone; however, the relapse rates for all stages of testicular lymphoma are high despite systemic therapy. For Stage II disease and higher, chemotherapy/radiation is recommended; orchiectomy may not be mandatory.

Antineoplastic Combined Chemotherapy Protocols↗

Routine evaluation of the cervical spine in head-injured patients with dynamic fluoroscopy: a reappraisal.

BACKGROUND: The mechanism for clearing the cervical spine in patients with altered mental status remains controversial. Recommendations have ranged from removal of the cervical collar after 24 hours in patients with normal radiographs, to indefinite immobilization in a cervical collar, and recently cervical flexion-extension examinations using dynamic fluoroscopy. The purpose of this study was to evaluate the efficacy and safety of dynamic fluoroscopy flexion-extension examinations in identifying ligamentous cervical spine injury and clearing the cervical spine in patients with altered mental status after trauma. METHODS: Patients with a Glasgow Coma Scale score < 13 for greater than 48 hours after admission and normal cervical spine radiographs were candidates for fluoroscopic evaluation. The protocol required visualization of the entire cervical spine, through T1, through full extension and flexion under the direct supervision of a radiologist. Oblique fluoroscopic views were obtained, as necessary, to visualize the cervicothoracic junction. Demographic data, fluoroscopy time, total time per study, true and false positives and negatives, and complications were recorded. RESULTS: From July 1992 through December 1999, fluoroscopic examinations were performed on 301 patients. There were 297 true-negative examinations, 2 true-positive examinations (stable injuries), 1 false-negative examination, and 1 false-positive examination. The incidence of ligamentous injury identified by fluoroscopy in this study was 2 of 301 (0.7%). Unstable cervical spine ligamentous injuries were identified in only 0.02% of all trauma patients. One patient developed quadriplegia when fluoroscopic evaluation was performed after two protocol violations. CONCLUSION: Unstable cervical spine ligamentous injury without fracture is a rare occurrence. The cervical spine may be cleared after a normal cervical spine series (plain radiograph and computed tomographic scan) as recommended in the 1998 Eastern Association for the Surgery of Trauma guidelines. If dynamic fluoroscopy is to be used, adherence to the protocol, including review of the cervical spine radiographs before fluoroscopy and visualization of the entire cervical spine, C1-T1, is mandatory to ensure patient safety.

Adult↗