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Biomedical subjects

J M Novak

Publications and source records attributed to J M Novak.

At least 19 recordsLinked to original sources

Phosphorus sorption by sediments in a southeastern coastal plain in-stream wetland.

A close relationship has been reported between sediment organic C (SedOC) content and its P sorption capacity (P(max)) and total P (TP) concentration. Phosphorus sorbed to organically complexed cations is a proposed explanation for this relationship. The objectives of this study were (i) to determine relationships between in-stream wetland SedOC content and both the sediment's P(max) and TP concentrations, and (ii) to ascertain the role of both organically complexed and oxalate-extractable cations on the sediment P(max) and TP values. The sediment's oxalate-extractable Fe (Fe(ox)) and Al (Al(ox)) contents were determined using acidified ammonium oxalate, while sodium pyrophosphate was used to extract organically complexed cations (Al(pryo), Ca(pyro), Fe(pyro), Mg(pyro), and Mn(pyro)). Both the sediment's P(max) and TP contents were strongly correlated with its SedOC concentration (r(2) > 0.90, P < 0.001). Only the Al(ox) contents were significantly correlated with TP and P(max), suggesting that amorphous Al forms have an important role in P sorption. All five pyrophosphate-extracted cations were significantly correlated with SedOC contents. Regression analyses showed that the Al(pyro) accounted for 88% of the variation in sediment P(max) values, whereas a combination of Al(pyro) and Ca(pyro) accounted for 98% of the variation in sediment TP concentrations. Additionally, Al and Ca chelated by SedOC compounds also have an important role in P binding and indicate that a linkage exists between the wetlands SedOC and P(max) content and its ability to accumulate TP. This study identified that two different mechanisms have significant roles in regulating P sorption by sediments in a southeastern Coastal Plain in-stream wetland.

Adsorption↗

Element levels in snakes in South Carolina: differences between a control site and exposed site on the Savannah River site.

Levels of 18 elements, including lead, mercury, selenium, and uranium, were examined in three species of snakes from an exposed and reference site on the Department of Energy's Savannah River Site in South Carolina. We tested the hypotheses that there were no differences as a function of species, and there were no difference between the exposed and control site for blood and muscle (tail) samples for banded water snake (Nerodia fasciata), brown water snake (N. taxispilota) and cotton mouth (Akistrodon piscivorous). The banded water snakes collected were significantly smaller than the other two species. For blood, there were significant species differences only for barium, copper, selenium, uranium and zinc, while for muscle tissue there were significant interspecific differences in aluminum, arsenic, barium, cobalt, cesium, copper, iron, lead, mercury, manganese, strontium, vanadium and zinc, suggesting that muscle tissue in the tail is a better indicator of potential interspecific differences. It is also easier logistically to collect tail tissue than blood. Where one species had significantly higher levels than the other species in muscle tissue levels, cottonmouth had higher levels of five elements (aluminum, cobalt, lead, mercury, vanadium), brown water snake had two (lead, strontium), and banded water snake had only barium. There were few significant differences between the control and reference site for levels of blood, but several for muscle tissue. All three species had significantly higher levels of arsenic and manganese at Tim's Branch than the reference site, and nickel and uranium were significantly higher for banded water snake and cotton mouth, the larger species. Individuals with high exposure of one element were exposed to high levels of other elements.

Animals↗

Omega-3 fatty acid effect on alveolar bone loss in rats.

Gingival inflammation and alveolar bone resorption are hallmarks of adult periodontitis, elicited in response to oral micro-organisms such as Porphyromonas gingivalis. We hypothesized that omega (omega)-3 fatty acids (FA) dietary supplementation would modulate inflammatory reactions leading to periodontal disease in infected rats. Rats were fed fish oil (omega-3 FA) or corn oil (n-6 FA) diets for 22 weeks and were infected with P. gingivalis. Rats on the omega-3 FA diet exhibited elevated serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), documenting diet-induced changes. PCR analyses demonstrated that rats were orally colonized by P. gingivalis; increased IgG antibody levels substantiated this infection. P. gingivalis-infected rats treated with omega-3 FA had significantly less alveolar bone resorption. These results demonstrated the effectiveness of an omega-3 FA-supplemented diet in modulating alveolar bone resorption following P. gingivalis infection, and supported that omega-3 FA may be a useful adjunct in the treatment of periodontal disease.

Alveolar Bone Loss↗

An alum-based water treatment residual can reduce extractable phosphorus concentrations in three phosphorus-enriched coastal plain soils.

The accumulation of excess soil phosphorus (P) in watersheds under intensive animal production has been linked to increases in dissolved P concentrations in rivers and streams draining these watersheds. Reductions in water dissolved P concentrations through very strong P sorption reactions may be obtainable after land application of alum-based drinking water treatment residuals (WTRs). Our objectives were to (i) evaluate the ability of an alum-based WTR to reduce Mehlich-3 phosphorus (M3P) and water-soluble phosphorus (WSP) concentrations in three P-enriched Coastal Plain soils, (ii) estimate WTR application rates necessary to lower soil M3P levels to a target 150 mg kg(-1) soil M3P concentration threshold level, and (iii) determine the effects on soil pH and electrical conductivity (EC). Three soils containing elevated M3P (145-371 mg kg(-1)) and WSP (12.3-23.5 mg kg(-1)) concentrations were laboratory incubated with between 0 and 6% WTR (w w(-1)) for 84 d. Incorporation of WTR into the three soils caused a near linear and significant reduction in soil M3P and WSP concentrations. In two soils, 6% WTR application caused a soil M3P concentration decrease to below the soil P threshold level. An additional incubation on the third soil using higher WTR to soil treatments (10-15%) was required to reduce the mean soil M3P concentration to 178 mg kg(-1). After incubation, most treatments had less than a half pH unit decline and a slight increase in soil EC values suggesting a minimal impact on soil quality properties. The results showed that WTR incorporation into soils with high P concentrations caused larger relative reductions in extractable WSP than M3P concentrations. The larger relative reductions in the extractable WSP fraction suggest that WTR can be more effective at reducing potential runoff P losses than usage as an amendment to lower M3P concentrations.

Agriculture↗

Mechanical small bowel obstruction precipitated by colonoscopy.

Mechanical small bowel obstruction (SBO) is rare complication of colonoscopy. We present a patient who developed SBO 24 h after surveillance colonoscopy. Four years prior to this procedure, he had undergone augmentation cecocystoplasty with continent ileal conduit. He subsequently underwent laparotomy and lysis of a band adhesion that caused extrinsic compression of the ileum proximal to ileotransverse colostomy. We further review the literature, describe the salient features of colononoscopy-induced bowel obstruction, and identify the risk factors for this unusual complication.

Abdominal Pain↗

A computational approach for flow-acoustic coupling in closed side branches.

The quarter-wave resonator, which produces a narrow band of high acoustic attenuation at regularly spaced frequency intervals, is a common type of silencer used in ducts. The presence of mean flow in the main duct, however, is likely to promote an interaction between these acoustic resonances and the flow. The coupling for some discrete flow conditions leads to the production of both large wave amplitudes in the side branch and high noise levels in the main duct, thereby transforming the quarter-wave silencer into a noise generator. The present approach employs computational fluid dynamics (CFD) to model this complex interaction between the flow and acoustic resonances at low Mach number by solving the unsteady, turbulent, and compressible Navier-Stokes equations. Comparisons between the present computations and the experiments of Ziada [PVP-Vol. 258, ASME, 35-59 (1993)] for a system with two coaxial side branches show that the method is capable of reproducing the physics of the flow-acoustic coupling and predicting the flow conditions when the coupling occurs. The theory of Howe [IMA J. Appl. Math. 32, 187-209 (1984)] is then employed to determine the location and timing of the acoustic power production during a cycle.

Journal Article↗

Storm flow export of metolachlor from a coastal plain watershed.

During an 18-month (1994-1995) survey of the surface water in an Atlantic Coastal Plain watershed, metolachlor was most frequently detected during storm flow events. Therefore, a sampling procedure, focused on storm flow, was implemented in June of 1996. During 1996, three tropical cyclones made landfall within 150 km of the watershed. These storms, as well as several summer thunderstorms, produced six distinct storm flow events within the watershed. Metolachlor was detected leaving the watershed during each event. In early September, Hurricane Fran produced the largest storm flow event and accounted for the majority of the metolachlor exports. During the storm event triggered by Hurricane Fran, the highest daily average flow (7.5 m2 s-1) and highest concentration (5.1 micrograms L-1) ever measured at the watershed outlet were recorded. Storm flow exports leaving the watershed represented 0.1 g ha-1 or about 0.04% of active ingredient applied.

Acetamides↗

Pesticide concentration variations correlated with well bore volume removal in shallow coastal plain ground water.

The effects of well bore volume removal (Vn) on the concentration of alachlor [2-chloro-N-(2,6-diethylphenyl)-N-(methoxy methyl) acetamide] and prometon (6-methoxy-N,N'-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine] in ground water obtained from three monitoring wells installed in the Coastal Plain region of North Carolina was investigated. Seasonal effects were also investigated by conducting the exercise in February and May. In the majority of cases, the lowest pesticide concentrations occurred in the initial well bore volume (V1 = stagnant water). Removal of additional well bore volumes (V2 to V10) from two of the wells resulted in pesticide concentrations that did not vary substantially. This indicates that a representative aquifer sample was obtainable, in most cases from these wells, after removal of the initial well bore volume. In contrast, a third well required the purging of two well bore volumes before a stable alachlor concentration was achieved. Seasonal effects of bore volume removal vs. pesticide concentrations for the three wells were not significant (P > 0.05). It was concluded that a protocol for improved accuracy in pesticide analyses of ground water can be obtained by establishing a pesticide concentration-purging (well bore volume) relationship for each well.

Acetamides↗

Donor origin of a posttransplant liver allograft malignancy identified by fluorescence in situ hybridization for the Y chromosome and DNA genotyping.

Posttransplantation malignancy in the allograft is a rare complication of orthotopic liver transplantation. In the described case, an abnormal T-tube cholangiogram, performed 6 months after orthotopic liver transplantation between a male donor and a female recipient, prompted needle liver biopsy. A moderately differentiated adenocarcinoma was found. Fluorescence in situ hybridization for the Y chromosome indicated male origin of malignancy. Donor-related disease was confirmed by comparative DNA analysis of genomic sequences from the donor liver, associated tumor, and recipient peripheral blood. Results of these investigations qualified the recipient for a second liver transplant.

Adenocarcinoma↗

Evaluation of atrazine positive and false positive immunoassay detections in ground water.

False positive responses on an atrazine (6-chloro-N-ethyl-N'-(1-methylethyl)-1,3,5-triazine-2,4-diamine) immunoassay kit were investigated to explain possible causes for these occurrences. Ground water samples were evaluated with the immunoassay kit and positive responses (> 0.20 microgram L-1) were confirmed using gas chromatography/mass spectrometry (GC/MS). Non-confirming samples (false positives) were analyzed for seven additional compounds on GC. Resulting GC/MS and GC analyses showed that 70% of the false positives could be attributed to two compounds. Prometon (6-methoxy-N,N'-bis(1-methylethyl)-1,3,5-triazine-2,4-diamine) was responsible for the majority (64%) of the false positive responses The atrazine metabolite, deethylatrazine (2-chloro-4-amino-6-isopropylamino-1,3,5-triazine), was responsible for the other 6% of the false positives measured. Unattributed false positives (30%) were probably due to an overestimation of pesticide concentrations in the kit's lower detection range.

Atrazine↗

PCR-based screening for cystic fibrosis carrier mutations in an ethnically diverse pregnant population.

As the most common lethal autosomal recessive disorder in North America, cystic fibrosis (CF) is an obvious candidate for general population carrier screening. Although the identification of the causative gene has made detection of asymptomatic carriers possible, the extreme heterogeneity of its mutations has limited the sensitivity of the available DNA screening tests and has called into question their utility when they are applied to patients with no family history of the disease. The purpose of this study was to determine the technical feasibility, patient acceptance and understanding, and psychosocial impact of large-scale CF carrier screening in an ethnically diverse pregnant population. A total of 4,739 pregnant women attending prenatal clinics located in both an academic medical center and a large HMO were invited in person to participate. Of this group, 3,543 received CF instruction and assessments of knowledge and mood, and 3,192 underwent DNA testing for the six most common CF mutations, by means of a noninvasive PCR-based reverse-dot-blot method. Overall participation rates (ranging from 53% at the HMO to 77% at the academic center) and consent rates for DNA testing after CF instruction (>98%) exceeded those of most other American studies. The PCR-based screening method worked efficiently on large numbers of samples, and 55 carriers and one at-risk couple were identified. Understanding of residual risk, anxiety levels, and overall satisfaction with the program were acceptable across all ethnic groups. Our strategy of approaching a motivated pregnant population in person with a rapid and noninvasive testing method may provide a practical model for developing a larger CF screening program targeting appropriate high-risk groups at the national level, and may also serve as a paradigm for population-based screening of other genetically heterogeneous disorders in the future.

Academic Medical Centers↗

Polymerase chain reaction-based K-ras mutation detection of pancreatic adenocarcinoma in routine cytology smears.

The cytologic diagnosis of pancreatic carcinoma is notoriously difficult, particularly in distinguishing benign atypia from well-differentiated adenocarcinoma. Mutation of codon 12 in the K-ras oncogene is frequently found with pancreatic cancers. Detection by polymerase chain reaction (PCR) followed by restriction endonuclease digestion can provide a powerful tool to improve and confirm diagnosis. The authors examined the utility of PCR-based detection in the diagnosis of pancreatic carcinoma using routinely obtained cytology smears that could be collected at most hospitals. Pancreatic cytology smears were collected retrospectively from 60 patients. DNA was extracted from the slides and amplified by PCR using mismatched primers that generated a Bst-N1 recognition site with the wild type codon 12 but not with the mutant allele. Results were compared with clinical follow-up. K-ras codon 12 mutations were observed in 44 of 46 (95.7%) cases of pancreatic cancer, but not in 12 benign cases nor in 2 cases of islet cell tumor. The amplification and digestion steps proved robust and sensitive, capable of detecting mutant K-ras alleles from cytology smears that contained only small foci of suspicious cells. Our results indicate that K-ras mutation analysis can be done reliably within 1 to 2 days from routine cytology slides without special handling, increasing the sensitivity of diagnosis in ambiguous cases while maintaining cost-effective and relatively noninvasive sampling strategy.

Adenocarcinoma↗

Minimal or no cancer in radical prostatectomy specimens. Report of 13 cases of the "vanishing cancer phenomenon".

Early detection efforts identify prostate cancer at lower clinical and pathologic stages, often resulting in smaller volumes of tumor in radical prostatectomy specimens. In some cases, complete sampling of the radical prostatectomy specimen for biopsy-proven adenocarcinoma reveals minimal or no residual cancer. We evaluated the clinical and pathologic findings in 13 such cases in an effort to document this finding, which we refer to as the "vanishing cancer phenomenon." The mean number of prostate slides examined per case was 79 (range, 34-248). Carcinoma was absent in two cases, present in a single focus in eight cases, and present in two foci in three cases. Mean cancer volume in the 10 cases with residual tumor was 0.019 cc (range, 0.003-0.038); the largest single dimension of any tumor focus was 3 mm. All cancers were well differentiated or moderately differentiated in the biopsy and prostatectomy. Our results indicate that in some cases cancer may be extremely difficult or impossible to find in the prostatectomy specimen despite exhaustive sampling. The incidence of this "vanishing cancer phenomenon" is probably increasing because more low-stage cancers are being treated by prostatectomy. The inability to identify cancer in a prostate removed for needle biopsy-proven carcinoma may not indicate technical failure.

Adenocarcinoma↗

Characterization of substance P binding to human monocytes/macrophages.

Substance P (SP), a member of the tachykinin family of neuropeptides, can immunomodulate human T cells and monocytes. SP has been shown to stimulate human monocytes to produce inflammatory cytokines and superoxide ions, and it enhances tumoricidal activity in vitro. A specific SP receptor, however, has not been identified on human monocytes/macrophages. In this study, we report that 125I-SP binds to human monocytes/macrophages with high affinity and specificity (Kd = 2.7 x 10(-8) to 5.5 x 10(-8) M). Our measurements of binding affinity to this single class of receptors were possible only when experiments were performed in the presence of excess serine proteinase inhibitor (serpin) enzyme complex receptor ligand. We determined that 125I-SP bound to a specific receptor on human monocytes/macrophages and that this binding was detectable as early as 6 h and was maintained throughout 6 to 8 weeks in culture. Modulation of the diverse immunological and inflammatory effects of SP on human monocytes may be mediated through this specific SP receptor.

Humans↗

Functional characterization of protease-treated Bacillus anthracis protective antigen.

Characterization of the functional domains of Bacillus anthracis protective antigen (PA, 83-kDa), the common cellular binding molecule for both anthrax edema toxin and anthrax lethal toxin, is important for understanding the mechanism of entry and action of the anthrax toxins. In this study, we generated both biologically active (facilitates killing of J774A.1 cells in combination with lethal factor, LF) and inactive preparations of PA by protease treatment. Limited proteolytic digestion of PA in vitro with trypsin generated a 20-kDa fragment and a biologically active 63-kDa fragment. In contrast, limited digestion of PA with chymotrypsin yielded a preparation containing 37- and 47-kDa fragments defective for biological activity. Treatment with both chymotrypsin and trypsin generated three major fragments, 20, "17," and 47 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This PA preparation was also biologically inactive. To investigate the nature of the defect resulting from chymotrypsin treatment, we assayed PA preparations for the ability to bind to the cellular receptor and to bind and internalize 125I-LF. All radiolabeled PA preparations bound with specificity to J774A.1 cells and exhibited affinities similar to native 83-kDa PA. Once bound to the cell surface receptor, both trypsin-treated PA and chymotrypsin/trypsin-treated PA specifically bound 125I-LF with high affinity. Finally, these PA preparations delivered 125I-LF to a Pronase-resistant cellular compartment in a time- and temperature-dependent fashion. Thus, the biological defect exhibited by chymotrypsin-treated PA is not at the level of cell binding or internalization but at a step later, such as toxin routing or processing by J774A.1 cells. These protease-treated preparations of PA should prove useful in both elucidating the intracellular processing of anthrax lethal toxin and determining the structure-function relationship of PA and LF.

Animals↗

Effect of osmotic pressure on uptake of chemotherapeutic agents by carcinoma cells.

Intraperitoneal chemotherapy has been used to treat cancers which are confined to the abdominal cavity. Several variables which affect drug delivery into tumor cells have been identified, but the effect of osmotic pressure has not been studied. Tumor cell lines were used to evaluate the effect of fluid tonicity on drug uptake. HeLa cells and a murine teratoma cell line were suspended in solutions of tonicities 154, 308, and 616 mosM, each containing the same quantity of 5-fluorouracil, and uptake of the drug was measured at different intervals over 30 min. At all time points the amount of 5-fluorouracil taken up by cells in solutions of 154 mosM was greater than that in 310 mosM solutions, which was greater than the uptake in 616 mosM solutions, each by an average of 40-50%. Incorporation of drug into tumor cells was also assayed in vivo using a teratoma cell line propagated i.p. in mice. Tumor cell uptake of doxorubicin was increased to a similar extent when this drug was administered in hypotonic solutions of 154 mosM and was decreased by administration in hypertonic solutions of 465 mosM, as compared to solutions of 310 mosM. These results demonstrate that the uptake of chemotherapeutic agents into tumor cells is increased significantly when these drugs are infused in solutions of lower osmolalities, a finding which may be exploited in clinical situations.

Animals↗

Effect of volume and pH on surface receptor number in macrophages.

Incubation of rabbit alveolar macrophages in hypo-osmotic solutions transiently increases cell volume and inhibits membrane internalization, resulting in an increase in surface receptor number. Since recent reports suggest that hypo-osmotic treatment decreases intracellular pH, and that reduced pH inhibits receptor internalization, pH was measured in hypo-osmotically treated macrophages. We found that cells incubated in iso-osmotic solutions of pH less than 7.2 exhibited a decrease in intracellular pH upon exposure to hypo-osmotic solutions, while cells in iso-osmotic solutions of pH greater than 7.2 had an increase in pH upon exposure to hypo-osmotic solutions. The relative increase in surface receptor number was unaffected by the initial pH or by the direction of change in pH. Incubation of cells in high K+/low Na+ hypotonic buffers induced a persistent increase in cell volume and surface receptor number. Cell volume and surface receptor number fell to baseline values after restoration of isotonicity by the addition of hypertonic sucrose. These manipulations had little effect on intracellular pH. We conclude that the inhibition of membrane internalization observed in cells exposed to hypo-osmotic solutions is independent of changes in intracellular pH. The inhibition of internalization observed in this system may be due directly to forces produced as a consequence of cell swelling.

Animals↗