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Biomedical subjects

J R Wagner

Publications and source records attributed to J R Wagner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Biases associated with genotype and sex in prediction of fat-free lean mass and carcass value in hogs.

Carcass and live measurements of 165 market hogs that represented seven genotypes were used to investigate genotype and sex biases associated with the prediction of fat-free lean mass (FFLM) and carcass value. Carcass value was determined as the sum of the product of weight of individual cuts and their average unit prices adjusted for slaughter and processing costs. Independent variables used in the prediction equations included carcass measurements, such as optical probe, midline ruler, ribbed carcass measurements, and electromagnetic scanning (EMSCAN), and live animal ultrasonic scanning. The effect of including subpopulation mean values of independent variables in the prediction equations for FFLM and carcass value was also investigated. Genotype and sex biases were found in equations in which midline backfat, ribbed carcass, EMSCAN, and live ultrasonic scanning were used as single technology sets of measurements. The prediction equations generally undervalued genotypes with above-average carcass value. Biases were reduced when measurements of combined technologies and mean adjusted variables were used. The FFLM and carcass value of gilts were underestimated, and they were overestimated of barrows. Equations that combined OP and EMSCAN technologies were the most accurate and least biased for both FFLM and carcass value. Equations that included carcass weight and midline last-rib backfat thickness measurements were the least accurate and most biased. Genotype and sex biases must be considered when predicting FFLM and carcass value.

Adipose Tissue↗
PubMed1997

Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice.

Inheritance of an inactivated form of the VHL tumor suppressor gene predisposes patients to develop von Hippel-Lindau disease, and somatic VHL inactivation is an early genetic event leading to the development of sporadic renal cell carcinoma. The VHL gene was disrupted by targeted homologous recombination in murine embryonic stem cells, and a mouse line containing an inactivated VHL allele was generated. While heterozygous VHL (+/-) mice appeared phenotypically normal, VHL -/- mice died in utero at 10.5 to 12.5 days of gestation (E10.5 to E12.5). Homozygous VHL -/- embryos appeared to develop normally until E9.5 to E10.5, when placental dysgenesis developed. Embryonic vasculogenesis of the placenta failed to occur in VHL -/- mice, and hemorrhagic lesions developed in the placenta. Subsequent hemorrhage in VHL -/- embryos caused necrosis and death. These results indicate that VHL expression is critical for normal extraembryonic vascular development.

Animals↗
PubMed1997

Pulmonary infarcts can mimic pulmonary metastases from renal cancer.

PURPOSE: Spontaneous regression of pulmonary metastases from renal cell carcinoma is a rare but well documented event. We present 2 recent cases that were radiographically consistent with pulmonary metastases from renal cell carcinoma but were pathologically shown to be pulmonary infarcts with no evidence of metastatic cells. Stable pulmonary infarcts can be misconstrued as metastatic disease in patients with renal cell carcinoma while resolving pulmonary infarcts may represent a subpopulation of patients with apparent spontaneous regression. Clinical implications of these findings are discussed. MATERIALS AND METHODS: Clinical and pathological data from 2 patients with large primary renal tumors, venous thrombi and lung masses were reviewed. Data from these cases, as well as pertinent urological and pathological literature, are presented. RESULTS: Although preoperative assessment was consistent with stage IV renal cell carcinoma, pathological examination of the lung masses in these patients showed no evidence of tumor cells. CONCLUSIONS: Pulmonary infarcts may mimic resolving or stable pulmonary metastasis in patients with renal cell carcinoma. Accurate clinical staging is crucial for the prognosis and treatment of renal cell carcinoma. Mistaking pulmonary infarcts for metastatic lesions can lead to inaccurate prognoses and inappropriate treatment.

Carcinoma, Renal Cell↗
PubMed1997

Changes in apoptosis of human polymorphonuclear granulocytes with aging.

Many alterations with aging occur at the cellular and organic levels in the immune system ultimately leading to a decrease in the immune response. Our aim in the present work was to study apoptosis of polymorphonuclear granulocytes (PMN) with aging under various stimulations since apoptosis might play an important role in several pathologies encountered with aging. The PMN of healthy young (20-25 years) and elderly (65-85 years) subjects were examined after 24 h of sterile culture with and without stimulation. The stimulating agents included: phorbol myristate acetate (PMA), hydrogen peroxide (H2O2), N-formyl-methionyl-leucyl phenylalanine (FMLP), granulocyte-macrophage colony stimulating factor (GM-CSF), reduced glutathione (GSH), lipopolysaccharide (LPS) and interleukin 2 (IL-2). Apoptosis was assessed by traditional staining of the plates, by flow cytometric staining and DNA gel electrophoresis. It was found that without stimulation the susceptibility of PMN to apoptosis was slightly increased with aging. Under various stimulations, such as PMA. H2O2, apoptosis was almost 100%, while the treatment by FMLP, oxLDL and GSH did not change its extent in PMN obtained either from young or elderly subjects. Marked age-related changes were observed in the extent of apoptosis under stimulation with GM-CSF, IL-2 and LPS. These agents were able to significantly prevent apoptosis in PMN of young subjects, while only the GM-CSF was able to slightly modulate it in neutrophils of elderly subjects. From these results, we suggest that changes in apoptosis of PMN with aging could play a role in the increased incidence of certain immune system related pathologies of aging, such as cancer, infections and autoimmune disorders.

Adult↗
PubMed1997

Laparoscopic adrenalectomy: a new standard of care.

OBJECTIVES: Adrenalectomy is the mainstay of treatment for adrenal tumors. A variety of surgical approaches to the adrenal gland have been described. We studied the feasibility of laparoscopic adrenalectomy (LA), compared laparoscopic with open adrenalectomy (OA), and studied the hemodynamic changes in patients with pheochromocytoma. METHODS: Our early experience with 20 consecutive LAs is compared with a contemporaneous, matched control cohort of 20 patients who underwent OA via a flank or subcostal incision. LA was performed via a transperitoneal approach, following a standardized surgical technique. RESULTS: LA was successfully completed in 18 of 20 cases. Average operating time in the first 5 cases was 261 minutes, but, with further experience, a significant decrease in operative time was seen in the last cohort of 4 patients (155 minutes) (P = 0.0018). There was no significant difference in operative time or degree of blood loss between LA and OA groups. Patients who underwent LA required lower doses of postoperative parenteral narcotics (P = 0.0169), had a shorter hospital stay (mean 3.2 days) (P < 0.0001), and had a shorter convalescent period (mean 3.1 weeks) (P < 0.0001). Complications in the laparoscopic group (chronic port site pain in 1 patient, intra-abdominal fluid collection in another) occurred in the 2 patients who required open conversion. These 2 patients had large adrenal tumors (9 and 7 cm in diameter, respectively). LA resulted in similar hemodynamic changes as OA in patients with pheochromocytoma. CONCLUSIONS: LA is a safe and effective approach in most patients with adrenal pathology. Benefits include excellent operative exposure and visualization, less postoperative pain, shorter hospital stay and convalescent period, and improved cosmetic result. Pheochromocytoma is not a contraindication to LA. Patients with large adrenal tumors (larger than 6 cm), evidence of venous involvement, or invasion into surrounding tissue should be approached cautiously.

Adrenal Gland Neoplasms↗
PubMed1997

Perirenal myelolipoma.

Extra-adrenal myelolipomas are rare, benign tumors composed of hematopoietic and adipose elements. Although these tumors can cause local symptoms or hemorrhage, they are generally asymptomatic. However, when discovered intraoperatively, they pose a diagnostic dilemma to the urologic surgeon. We present a case of perirenal extra-adrenal myelolipoma discovered intraoperatively in a patient with von Hippel-Lindau disease undergoing partial nephrectomy.

Adrenal Gland Neoplasms↗
PubMed1997

Renal cancer: preoperative evaluation with dual-phase three-dimensional MR angiography.

PURPOSE: To evaluate the use of dual-phase three-dimensional magnetic resonance (MR) angiography in the preoperative staging of renal cancer. MATERIALS AND METHODS: MR angiography was performed in 18 patients before performance of partial (n = 7), radical (n = 10), or laparoscopic (n = 1) nephrectomy to treat renal cancer. Dynamic, three-dimensional MR angiograms were obtained with gadoteridol enhancement, breath holding, and a three-dimensional spoiled gradient-echo sequence. Images were obtained at 15-second intervals to achieve opacification of arteries and veins. Source, maximum intensity projection, and multiplanar reconstruction images were evaluated. Imaging results were compared with surgical findings. RESULTS: Renal arterial phase MR angiograms depicted 30 of 31 (97%) surgically confirmed renal arteries, with one false-positive result (an artery that arose from an early-branching single main renal artery, interpreted as a separate accessory artery). Renal venous phase MR angiograms depicted all seven instances of renal vein involvement, including extension to the inferior vena cava in two patients. Collateral vessels around the tumor, including prominent gonadal veins in three patients, were demonstrated. Additional findings included adenopathy and adrenal and pulmonary metastases. CONCLUSION: Dual-phase MR angiography of the kidney may be a useful technique in depicting renal vessels before nephrectomy.

Carcinoma, Renal Cell↗
PubMed1997

Incorporation of two deoxycytidine oxidation products into cellular DNA.

The oxidation of cytosine in DNA by free radicals and other oxidants leads to an assortment of products including pyrimidine ring 5,6-saturated, 5,6-unsaturated, contraction, and fragmentation products. The formation of these products in cellular DNA may explain in part the preponderance of C to T transitions induced spontaneously and by H2O2 or ionizing radiation. Our studies have focused on the biological effects of two major 5,6-unsaturated oxidation products of cytosine: 5- hydroxycytosine and 5-hydroxyuracil. In the present work, we have attempted to study the repair of these two lesions by specifically incorporating them into cellular DNA upon incubation of cells with 5-hydroxy-2'deoxycytidine and 5-hydroxy-2'-deoxyuridine. Incubation of mouse L1210 cells with 250 M 5-hydroxy-2'-deoxycytidine led to the incorporation of this lesion to a level 20 times higher (43 lesions/10(5) cytosines) than base-line levels; however, there was no evidence for its repair following a 15-h chase. In contrast, we did not observe any significant incorporation of 5-hydroxy-2'-deoxyuridine into the DNA of L1210 cells but did observe an unidentified product, presumably an oxidation product. This unidentified pyrimidine was incorporated at a very high level (about 2000 lesions/10(5) cytosine residues) and then partially repaired in chase experiments.

Animals↗
PubMed1996

Post-transcriptional regulation of vascular endothelial growth factor mRNA by the product of the VHL tumor suppressor gene.

The VHL tumor suppressor gene is inactivated in patients with von Hippel-Lindau disease and in most sporadic clear cell renal carcinomas. Although VHL protein function remains unclear, VHL does interact with the elongin BC subunits in vivo and regulates RNA polymerase II elongation activity in vitro by inhibiting formation of the elongin ABC complex. Expression of wild-type VHL in renal carcinoma cells with inactivated endogenous VHL resulted in unaltered in vitro cell growth and decreased vascular endothelial growth factor (VEGF) mRNA expression and responsiveness to serum deprivation. VEGF is highly expressed in many tumors, including VHL-associated and sporadic renal carcinomas, and it stimulates neoangiogenesis in growing solid tumors. Despite 5-fold differences in VEGF mRNA levels, VHL overexpression did not affect VEGF transcription initiation or elongation as would have been suggested by VHL-elongin association. These results suggest that VHL regulates VEGF expression at a post-transcriptional level and that VHL inactivation in target cells causes a loss of VEGF suppression, leading to formation of a vascular stroma.

Animals↗
PubMed1996

Increased susceptibility of low-density lipoprotein (LDL) to oxidation by gamma-radiolysis with age.

The susceptibility to oxidation of freshly isolated LDL from healthy normolipidemic individuals in three age groups was estimated by exposure of LDL to ionizing radiation followed by analyses of vitamin E, TBARS, conjugated dienes, and fluorescent products. The results clearly showed that LDL from elderly subjects was the most susceptible to oxidative damage in vitro. In particular, the greater susceptibility of LDL from elderly subjects in comparison to that from young subjects may be attributed to the much lower (4-fold) concentration of LDL vitamin E in the elderly subjects. The present study reinforces the notion that the susceptibility of LDL to oxidation increases with age.

Adult↗
PubMed1996

Excision of oxidative cytosine modifications from gamma-irradiated DNA by Escherichia coli endonuclease III and human whole-cell extracts.

The possible release from gamma-irradiated DNA of eight oxidatively modified cytosine bases by Escherichia coli endonuclease III was examined by trimethylsilylation and gas chromatography/electron impact/mass spectrometry. The results indicated that endonuclease III induced the release of 5-hydroxyhydantoin (1), 5-hydroxyuracil (2), cis-uracil 5,6-glycol (3), 5-hydroxycytosine (4), trans-uracil 5,6-glycol (5), and trans-1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine (8). The release of these products increased with the initial amount of damage in DNA, i.e., the dose of gamma-radiation (0-100 Gy), giving 4.6 +/- 1.0 fmol of 1, 5.8 +/- 0.3 fmol of 2, 4.9 +/- 0.5 fmol of 3, 11.2 +/- 1.2 fmol of 4, 10.7 +/- 2.1 fmol of 5, and 1.5 +/- 0.5 fmol of 8, per microgram DNA per 10 Gy. In addition, we estimated that the relative rates of excision were 5 approximately equal to 3 > (1.2-fold) 1 > (1.5-fold) 4 > (3.3-fold) 2 on the basis of their initial yields in DNA and initial rates of release as a function of incubation time. The excision of 5-hydroxyuracil (2) and 5-hydroxycytosine (4) lesions was studied in greater detail by enzymatic digestion and HPLC coupled to electrochemical (EC) detection which determines the amounts of these products in DNA. The results showed that the excision of 4 was more efficient than that of 2 (2.7-fold) with greater than 50% of the lesions remaining in DNA after treatment. Finally, we examined the excision of products 2 and 4 from irradiated DNA (50 Gy) by whole human cell extracts. The release of product 2 into the hydrosylate was 5.2 +/- 1.4 fmol per microgram of DNA as measured by fluorobenzylation coupled to gas chromatography/electron capture negative-ion chemical ionization/mass spectrometry. In identical samples, the amount of product 2 was reduced by 45.0 +/- 2.6% (225 from 500 fmol per microgram of DNA) and that of product 4 by 7.0 +/- 3.1% (42 from 600 fmol per microgram of DNA) as measured by HPLC/EC analysis.

Animals↗
PubMed1996

Renal arterioureteral hemorrhage: a complication of acucise endopyelotomy.

The Acucise ureteral catheter is a ureteral cutting balloon device that recently received approval for retrograde endopyelotomy. We report a case of a postoperative lower pole renal arterioureteral hemorrhage after retrograde endopyelotomy requiring interventional radiographic treatment. Significant gross hematuria after Acucise endopyelotomy may indicate a communication between the vasculature and collecting system. Prompt arteriography with embolization should be considered in this clinical situation.

Adult↗
PubMed1996

Congenital posterior urethral perineal fistulae: a unique form of urethral duplication.

Three unique cases of urethral duplication, often referred to as congenital posterior urethral perineal fistulae, are presented. Presenting signs and symptoms, evaluation, and treatment are discussed, and the literature is reviewed. Although labeled as a fistula in the literature, this entity most likely represents a distinct type of urethral duplication. A functional dorsal urethra separates it from the other forms of urethral duplication.

Abnormalities, Multiple↗
PubMed1996

Direct measurement of blood flow in the human bladder.

PURPOSE: We evaluated blood flow in the human bladder. MATERIALS AND METHODS: In 8 surgical cases a laser Doppler flow probe was placed in the bladder dome and anterior wall. In 10 endoscopic cases the flow probe was placed in the bladder trigone and lateral wall. RESULTS: Bladder filling resulted in reduced mean blood flow in the dome and anterior wall. After prostatectomy blood flow decreased in the dome but not the anterior wall. During endoscopy bladder filling resulted in diminished blood flow. CONCLUSIONS: Laser Doppler flowmetry can measure blood flow changes in the human bladder.

Aged↗
PubMed1996

Molecular genetics of renal cell carcinoma.

Renal cell carcinoma can be divided into sporadic and inheritable forms. One of the most common inheritable forms occurs in von Hippel-Lindau disease (VHL). VHL is a multisystem neoplastic disorder in which individuals develop tumors and cysts in multiple organs including the kidneys. Careful linkage analysis and cloning identified the VHL gene on chromosome 3p. In accordance with Knudson's hypothesis and tumor suppression theory, the VHL gene has been shown to have an important role in sporadic renal carcinoma as well. Further understanding of the VHL protein is likely to enhance our understanding of renal carcinogenesis, and clinical implications are beginning to evolve.

Carcinoma, Renal Cell↗
PubMed1996

Evolution of a legacy system to a Web patient record server: leveraging investment while opening the system.

A layered system is under development to enhance our legacy system as a backend in a WEB-enabled system. Each layer of the system has defined functionality, leverages the investment in the layer below, and follows the strategy of reducing support requirements for workstations. The mainframe system provides administrative integration of sub-systems, security, and the central data repository for most information. The second layer is a graphical user interface (GUI) to the system for Windows platforms. Support needs are limited by relying chiefly on X-terminals and application servers. The "Intranet" layer is a WEB Server building upon the second layer gateways to provide platform-independent access to selected information and images. The fourth layer, under evaluation, will extend access to the central data repository for Internet users of web browsers that support private-key/public-key encryption.

Computer Communication Networks↗
PubMed1995

Methylene blue-mediated photooxidation of 7,8-dihydro-8-oxo-2'-deoxyguanosine.

One well known product of the methylene blue-mediated photosensitization of 2'-deoxyguanosine (dG) in oxygen saturated aqueous solution is 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG). We observed that the rate of 8-oxodG photodecomposition by methylene blue-mediated photosensitization is approx. 3-times faster than for dG. The primary products of the methylene blue-mediated photosensitization of 8-oxodG are 2-amino-5-((2-deoxy-beta-D-erythro-pentofuranosyl)amino)-4H-imidazol-4-o ne (dIz), 2,2-diamino-4-((2-deoxy-beta-D-erythro-pentofuranosyl)amino)-5(2H)-oxazo lone (dZ), the 4R* and 4S* diastereoisomers of 4,8-dihydro-4-hydroxy-8-oxo-2'-deoxyguanosine (dO), and an as yet unidentified product with a molecular weight of 287 (dX). Except for the latter product, these compounds have all been identified following the methylene blue-mediated photooxidation of dG. Methylene blue-mediated photooxidation of 8-oxodG in D2O instead of H2O leads to a 4-fold increase in the rate of 8-oxodG photodecomposition while the addition of sodium azide retards the reaction, observations which imply that the reaction occurs via a type II (singlet oxygen mediated) mechanism. Like 8-oxodG, dIz and dZ are sensitive to hot piperidine and likely contribute to strand breaks observed in double stranded DNA exposed to methylene blue plus light followed by hot piperidine. Because 8-oxodG generates predominately G-->T transversions, the photooxidation of 8-oxodG to dIz, dO, and dX may explain the predominance of G-->C transversions in single-stranded M13mp2 bacteriophage DNA exposed to methylene blue plus light and then transfected into SOS-induced Escherichia coli.

8-Hydroxy-2'-Deoxyguanosine↗