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Biomedical subjects

J L Robertson

Publications and source records attributed to J L Robertson.

At least 19 recordsLinked to original sources

Complexity, fractals, disease time, and cancer.

Despite many years of research, a method to precisely and quantitatively determine cancer disease state remains elusive. Current practice for characterizing solid tumors involves the use of varying systems of tumor grading and staging and thus leaves diagnosis and clinical staging dependent on the experience and skill of the physicians involved. Although numerous disease markers have been identified, no combination of them has yet been found that produces a quantifiable and reliable measure of disease state. Newly developed genomic markers and other measures based on the developing sciences of complexity offer promise that this situation may soon be changed for the better. In this paper, we examine the potential of two measures of complexity, fractal dimension and percolation, for use as components of a yet to be determined "disease time" vector that more accurately quantifies disease state. The measures are applied to a set of micrographs of progressive rat hepatoma and analyzed in terms of their correlation with cell differentiation, ratio of tumor weight to rat body weight and tumor growth time. The results provide some support for the idea that measures of complexity could be important elements of any future cancer "disease time" vector.

Animals↗

Hysteretic spin-density-wave ordering in confined geometries.

We have measured the antiferromagnetic spin-density-wave (SDW) order in Cr/Cr(97.5)Mn2.5(001) superlattices. The Mn doping creates a high Néel temperature layer that confines the incommensurate SDW order within the Cr layers. With temperature cycling we observe a transition from commensurate to incommensurate SDW order and discrete changes in the SDW period. We find that these transitions show significant hysteresis (up to 75 K) when the number of SDW nodes within the Cr layer changes by an odd number, while there is no hysteresis for changes of an even number of nodes. This results from the competition between maintaining the spin structure at the interfaces and introducing a spin slip at the nodes of the Cr SDW.

Journal Article↗

CD44-deficient mice exhibit enhanced hepatitis after concanavalin A injection: evidence for involvement of CD44 in activation-induced cell death.

Administration of Con A induces severe injury to hepatocytes in mice and is considered to be a model for human hepatitis. In the current study, we investigated the role of CD44 in Con A-induced hepatitis. Intravenous administration of Con A (20 mg/kg) caused 100% mortality in C57BL/6 CD44-knockout (KO) mice, although it was not lethal in C57BL/6 CD44 wild-type (WT) mice. Administration of lower doses of Con A (12 mg/kg body weight) into CD44 WT mice induced hepatitis as evident from increased plasma aspartate aminotransferase levels accompanied by active infiltration of mononuclear cells and neutrophils, and significant induction of apoptosis in the liver. Interestingly, CD44 KO mice injected with similar doses of Con A exhibited more severe acute suppurative hepatitis. Transfer of spleen cells from Con A-injected CD44 KO mice into CD44 WT mice induced higher levels of hepatitis when compared with transfer of similar cells from CD44 WT mice into CD44 WT mice. The increased hepatitis seen in CD44 KO mice was accompanied by increased production of cytokines such as TNF-alpha, IL-2 and IFN-gamma, but not Fas or Fas ligand. The increased susceptibility of CD44 KO mice to hepatitis correlated with the observation that T cells from CD44 KO mice were more resistant to activation-induced cell death when compared with the CD44 WT mice. Together, these data demonstrate that activated T cells use CD44 to undergo apoptosis, and dysregulation in this pathway could lead to increased pathogenesis in a number of diseases, including hepatitis.

Adjuvants, Immunologic↗

Large harmonic softening of the phonon density of states of uranium.

Phonon density-of-states curves were obtained from inelastic neutron scattering spectra from the three crystalline phases of uranium at temperatures from 50 to 1213 K. The alpha-phase showed an unusually large thermal softening of phonon frequencies. Analysis of the vibrational power spectrum showed that this phonon softening originates with the softening of a harmonic solid, as opposed to vibrations in anharmonic potentials. It follows that thermal excitations of electronic states are more significant thermodynamically than are the classical volume effects. For the alpha-beta and beta-gamma phase transitions, vibrational and electronic entropies were comparable.

Journal Article↗

Aural abscesses in wild-caught box turtles (Terapene carolina): possible role of organochlorine-induced hypovitaminosis A.

Wild-caught box turtles (Terapene carolina carolina) with aural abscesses were observed over a period of several years. Histopathologic evaluation of epithelial tissues (conjunctiva, pharynx, trachea, auditory tube) revealed mucosal hyperplasia and squamous metaplasia, and accumulated keratin-like material in the middle ear cavity. These manifestations suggested the possibility of vitamin A deficiency. A nonsignificant trend toward reduced serum and hepatic vitamin A levels was observed in turtles with abscesses (mean serum and hepatic vitamin A levels 71 and 49% of respective levels in turtles without abscesses). Three organochlorine (OC) compounds (alpha-benzene hexachloride, heptachlor epoxide, and oxychlordane) and total (microg/g) OC compounds were significantly higher in turtles with abscesses compared with turtles without abscesses. No OC compounds were higher in turtles without abscesses compared with turtles with abscesses. These data suggest a possible effect of environmental chemicals on metabolism or utilization of vitamin A in wild box turtles, resulting in hypovitaminosis A.

Abscess↗

Suspected citrus pulp toxicosis in dairy cattle.

Thirteen lactating dairy cows from a herd of 650 died over a 6-week period. Most animals were down in milk production at 1 milking and were found dead at the next milking. Two cows had elevated heart rate and enlarged mandibular lymph nodes. Two others had azotemia, elevated heart rate, hyperglycemia, and weight loss. Necropsy of 10 cows revealed hemorrhages on the intestinal serosa and epicardium, lymphadenopathy, interstitial nephritis, small intestinal hemorrhage, and interstitial pneumonia. Histopathology showed lymphocytic to lymphogranulomatous inflammation in the heart, spleen, kidney, lymph nodes, liver, lung, pancreas, and adrenal gland. Phlebitis was present in 2 livers. The lesions resembled those of hairy vetch toxicosis, but no vetch was being fed. Similar lesions have been reported with the feeding of citrus pulp. Citrus pulp was being fed to the lactating cows and had been added to the diet 6 weeks before the first death. The syndrome resolved with elimination of citrus pulp from the diet.

Animals↗

Sporidesmin-induced mortality and histological lesions in mouse lines divergently selected for response to toxins in endophyte-infected fescue.

For eight generations, mouse lines were selected for smaller or larger reduction in postweaning gain from endophyte-infected fescue seed in the diet. After five generations in which there was no further selection for divergence in response to fescue toxicosis, the current experiment was conducted to determine whether resistant (R) and susceptible (S) lines differed in response to the mycotoxin sporidesmin (SPD). At approximately 8 wk of age, R and S mice that had never consumed endophyte-infected fescue seed were randomly assigned (five to seven per line x sex x SPD dose subclass) to receive dimethyl sulfoxide (DMSO) carrier or 10, 20, 30, or 40 mg/kg SPD by oral gavage. At death or euthanasia 14 d after treatment, livers and kidneys were collected for histological examination. Mice receiving 40 mg/kg SPD died sooner than mice receiving 30 mg/kg (63 vs 134 h; P = .02), but there was no line or line x dose interaction effect for time to death. Within those mice, neither line, dose, nor their interaction influenced liver weight or liver weight as a proportion of body weight. The R mice were more resistant to SPD than S mice; LD50 values were 23.6 and 31.8 mg/kg for the S and R lines, respectively (P < .05). Sporidesmin caused dose-related liver and kidney lesions in both lines. Selection lines did not differ significantly in the incidence of infarcts of hepatic lobules. However, at 30 and 40 mg/kg SPD doses, severity of this lesion was higher in affected S than in affected R mice. At the higher SPD doses, there also was a greater incidence of hepatic subacute cholangitis in S mice than in R mice. Foci of acute tubular necrosis were found in kidneys of mice receiving 20, 30, or 40 mg/kg SPD, with no protection against these lesions in the R line. Foci of tubular basophilia (indicative of tubular regeneration) were present in all line x dose subgroups, but incidence was not SPD dose-dependent in either line. In summary, divergent selection for weight gain response to ingestion of endophyte-infected fescue seed resulted in a favorable correlated response in survival following exposure to a chemically distinct toxin. It may be possible therefore, to select livestock populations for simultaneous resistance to a variety of toxins.

Acremonium↗

Development of a nomogram that predicts the probability of a positive prostate biopsy in men with an abnormal digital rectal examination and a prostate-specific antigen between 0 and 4 ng/mL.

OBJECTIVES: Early detection of prostate cancer traditionally involves both digital rectal examination (DRE) and serum prostate-specific antigen (PSA) determination in an informed patient population. Abnormalities in either of these studies typically lead to additional evaluations, including prostate biopsy. In this study, we analyzed the operational characteristics of serum PSA between 0 and 4 ng/mL as an initial test for prostate cancer. METHODS: From January 1990 through May 1997, transrectal biopsies were obtained from 700 men with a serum PSA level less than 4.0 ng/mL but DRE suspicious for cancer. Patient age, race, and serum PSA level were reviewed for this study. RESULTS: Of the 700 men studied, 445 were white (64%) and 255 were African American (36%). In multivariate analysis of prebiopsy risk factors (age, race, serum PSA), serum PSA was the only independent predictor of a positive prostate biopsy. A nomogram was created that determines the worst-case probability of a positive prostate biopsy in men with PSA between 0 and 4 ng/mL and a DRE suspicious for cancer. The predictions from the nomogram appeared accurate and discriminating, with a bias-corrected area under the receiver operating characteristic curve (i.e., comparison of the predicted probability with the actual outcome) of 0.75. CONCLUSIONS: Although early detection of prostate cancer has traditionally used both PSA measurement and DRE, PSA testing alone could be more easily implemented and may encourage some men to seek consultation who might not otherwise have done so. By providing a nomogram which provides a worse-case scenario (assuming a positive DRE) of the probability of a positive biopsy, the patient and clinician can make an informed decision as to whether additional evaluation is warranted.

Adult↗

Tilapia (Oreochromis niloticus) dosed with azathioprine display immune effects similar to those seen in mammals, including apoptosis.

Azathioprine, an anti-neoplastic drug and therapeutic immunosuppressant, was administered intraperitoneally at 10.0 and 50.0 mg/kg to 3-6-month-old tilapia (Oreochromis niloticus). Consistent alterations in immune cellular parameters of the blood, pronephros (hematopoietic kidney) and spleen were observed. Peripheral blood total cellularity decreased as the azathioprine dose increased, to approximately half that of the control. Differential analysis of white blood cells indicated a decline in lymphocyte number, in particular, with increased dosage of azathioprine. Pronephric total cellularity was depressed in fish receiving the 10.0 or 50.0 mg/kg dose. In contrast, both splenic weight and splenic total cellularity increased proportionately with the increase in the drug dosage. Histopathologic examination of the spleens showed normal patterns for both control and 10.0 mg/kg dose groups. At 50.0 mg/kg, spleens were characterized by marked expansion of the white pulp, although lymphocytes were rare. Melanomacrophage centers at the higher dose were also larger and more numerous than in the control group. Evaluation of splenic and pronephric leukocytes with apoptotic markers showed an increase in apoptotic cells in the pronephros with increasing drug dose. These changes in fish are consistent with those seen in humans and laboratory rodents dosed with azathioprine, suggesting that fish may be potentially useful as preliminary models for detecting immunosuppressive compounds.

Animals↗

Monitoring the susceptibility of citrus rust mite (Acari: Eriophyidae) populations to abamectin.

A citrus leaf disk bioassay was developed to monitor the susceptibility of citrus rust mite, Phyllocoptruta oleivora (Ashmead), populations to abamectin. Disks from leaves of several citrus cultivars were equally suitable bioassay substrates, and there was no difference in mortality when mites were sprayed directly or exposed to dry abamectin residue. The concentration-response relationship was determined at intervals over 2 yr for a reference population of citrus rust mites that had been maintained in culture and never exposed to acaricides. Three diagnostic concentrations of abamectin were selected based on the response of the reference population and were used to test the susceptibility of 15 populations of mites from commercial citrus groves. Comparisons with the reference population showed reduced levels of susceptibility in some populations. Populations of citrus rust mites from 6 commercial groves were sprayed twice in 1997 with combinations of acaricides designed to exert different intensities of selection pressure from abamectin. None of these populations showed a change in their response to abamectin in pre- and postspray bioassays, although their susceptibility was usually less than that of mites from the susceptible reference population. Biweekly counts of rust mites on fruit in these 6 groves suggested that, relative to groves which received no abamectin or 1 abamectin spray, mite control was not adversely affected in the groves sprayed twice with abamectin. The bioassay method is discussed in relation to factors that affect the interpretation of results from its use, and factors that may affect the development of resistance to abamectin in citrus rust mite populations are presented. This study has provided baseline data with which the results of ongoing tests of the response of citrus rust mite populations to abamectin can be compared.

Animals↗

Benzo[a]pyrene-induced hypocellularity of the pronephros in tilapia (Oreochromis niloticus) is accompanied by alterations in stromal and parenchymal cells and by enhanced immune cell apoptosis.

Numerous reports indicate that carcinogenic polycyclic aromatic hydrocarbons (PAH) are mammalian immunotoxicants. These environmental contaminants are widely distributed in both freshwater and costal marine ecosystems where they have been found to bioaccumulate in aquatic species, yet limited information exists regarding potential adverse effects of specific PAH on fish immune function. In the present report, Oreochromis niloticus fish (tilapia) were exposed by intraperitoneal injection to 5, 25, or 50 mg/kg of the PAH, benzo[a]pyrene (B[a]P). Histopathologic evaluation of the primary hematopoietic compartment of fish, the pronephros, demonstrated increased vacuolation of both stromal and parenchymal cells, reduction of lymphoid elements, and immune cell apoptosis. Total pronephros cell counts were diminished in a dose-dependent manner by the chemical exposure. The oxidative metabolic burst in phorbol myristate acetate (PMA)-simulated macrophages isolated from the pronephros was significantly inhibited by B[a]P, but only at the highest dose level employed. The phagocytic capacity of pronephros macrophages was not altered by the chemical treatment.

Animals↗

A toxicity study of eltenac, a nonsteroidal anti-inflammatory drug, in horses.

A double-blind study was performed, in horses, to determine the potential toxic effects of the nonsteroidal anti-inflammatory drug, eltenac(4-[(2,6-dichlorophenyl) amino]-3-thiopheneacetic acid). Four treatment groups of six horses were formed. The drug was injected intravenously, once daily, at a dose level of 0.5 mg/kg, 1.5 mg/kg or 2.5 mg/kg for 15 days. A control group was injected with sterile saline solution. Horses were monitored for changes in appetite, physical examinations, biochemical evaluations and gastroscopic examinations. Complete post-mortem examinations were also performed. A few glandular gastric ulcers, mild in severity, developed in seven animals during the treatment period. This occurred more often in horses treated with high doses of eltenac (P = 0.02). A dose-dependent change of white blood cell (WBC) count and neutrophil count was noted. Total protein, albumin and globulin levels had dose-dependent decreases. One horse in the high dose group (2.5 mg/kg) developed ventral ooedema as well as hypoproteinaemia. Gross post-mortem and histological examination did not reveal any signs of drug related gastrointestinal, renal or hepatic abnormalities. Toxic effects of eltenac given intravenously were greatest in horses treated with 2.5 mg/kg of the compound for 15 days compared to other groups.

Aniline Compounds↗

Interactions of recombinant and wild-type baculoviruses with classical insecticides and pyrethroid-resistant tobacco budworm (Lepidoptera: Noctuidae).

In tests with neonate Heliothis virescens (F.), we characterized interactions of all combinations of a recombinant Autographa californica (Speyer) nuclear polyhedrosis virus (AcAaIT) that expresses an insect-selective neurotoxin (AaIT) and wild-type AcNPV when combined with low concentrations of several conventional insecticides. All combinations of the recombinant virus AcAaIT and insecticides showed a positive interaction (decrease in the median lethal time (LT50) compared with the LT50 for either component alone). A type II pyrethroid (cypermethrin, which modifies currents of sodium channels) and a carbamate (methomyl, an inhibitor of acetylcholinesterase) were synergistic in combination with AcAaIT. Other insecticides also showed a positive interaction when tested in combination with the recombinant virus, but joint activity was slightly antagonistic (i.e., less than predicted activity when combined) with wild-type AcNPV. We also characterized the effectiveness of AcAaIT against pyrethroid-resistant H. virescens larvae. Our results show that a resistant strain of H. virescens is more sensitive to the recombinant virus compared with a susceptible strain. Results of these studies should be useful in planning of future field trials to increase the effectiveness of nuclear polyhedrosis viruses and to manage resistance to pyrethroids and other insecticides.

Animals↗

Effects of temperature on hematologic and serum biochemical profiles of hybrid striped bass (Morone chrysops x Morone saxatilis).

OBJECTIVE: To investigate the effect of water temperature on hematologic and biochemical analytes in hybrid striped bass. ANIMALS: Hybrid striped bass (reciprocal cross: female Morone chrysops x male M saxatilis) maintained in 2,000-L tanks with undergravel filters. PROCEDURE: Fish were acclimated to 10, 18, 24, and 29 C water for 6 weeks prior to sample collection. Hematologic and serum biochemical profiles were then determined. Values were compared among the various temperatures, and with reference intervals previously determined. RESULTS: Most values were within or slightly outside the established reference intervals. The following analytes deviated notably from the reference interval: leukocyte, lymphocyte, and monocyte counts were lower than the reference intervals at 10 C; glucose values were lower at 10 and 18 C; calcium values were higher at 10 and 18 C; and total protein, albumin, globulin, and chloride values were higher at 29 C. CONCLUSION: Separate reference intervals should be developed for analytes which, because of temperature, deviate notably from the reference interval. Modifications of the established reference intervals, by including fish from varied temperatures, should allow use of one reference interval for analytes, with only slight variation attributable to temperature. CLINICAL RELEVANCE: Determining the effects of temperature on the hematologic and biochemical values helps develop clinical pathology as a diagnostic tool in fish.

Acclimatization↗

Effects of ammonia and nitrate concentration on hematologic and serum biochemical profiles of hybrid striped bass (Morone chrysops x Morone saxatilis).

OBJECTIVE: To investigate the effects of poor water quality on hematologic and biochemical analytes in hybrid striped bass. ANIMALS: Hybrid striped bass (reciprocal cross: female Morone chrysops x male M saxatilis) maintained in 2,000-L tanks with undergravel filters. PROCEDURE: Fish were acclimated to high ammonia (0.15 mg/L) and nitrate (200 mg/L) concentrations for 6 weeks prior to sample collection. Hematologic and biochemical profiles were determined for these fish and for fish kept under normal conditions (control). Comparisons were made among the 3 water qualities and with reference intervals determined previously. RESULTS: Significant differences in hematologic and biochemical analytes were observed between fish in the various groups; however, most of the values were within established reference intervals. All values from fish in the high ammonia concentration tank were either within the reference interval or not significantly different from control values. Fish from the high nitrate concentration tank had higher serum creatinine values and lower chloride values than did control fish, and both analytes were substantially outside the reference intervals. CONCLUSION: High ammonia concentration of 0.15 mg/L did not affect any of the blood analytes measured. The hypercreatininemia and hypochloremia observed in fish from the 200 mg of nitrate/ml tank were considered to be pathologic changes associated with the high nitrate concentration. CLINICAL RELEVANCE: Determining the effects of water quality on hematologic and biochemical values helps to develop clinical pathology as a diagnostic tool in fish.

Alkaline Phosphatase↗

The effect of temperature and water quality on antibody response to Aeromonas salmonicida in sunshine bass (Morone chrysops x Morone saxatilis).

The kinetics of the antibody response to Aeromonas salmonicida were determined in sunshine bass (hybrid striped bass: female Morone chrysops X male Morone saxatilis) acclimated to 10, 18, 24, 29 degrees C, and to 0.15 mg 1(-1) un-ionized ammonia and 200 mg 1(-1) nitrate levels. Temperature and water quality factors affected the immune response of sunshine bass. Temperatures of 10 degrees C and 18 degrees C decreased the magnitude and delayed the time of the antibody response to A. salmonicida. The antibody response was not affected at 29 degrees C, which is above the optimal temperature for sunshine bass. Elevated un-ionized ammonia concentrations of 0.15 mg 1(-1) also did not affect the antibody response. Elevated nitrate levels of 200 mg 1(-1), however, decreased the antibody response to the same extent as 18 degrees C water.

Aeromonas↗

Genetic relatedness of North American populations of Tomicus piniperda (Coleoptera:Scolytidae).

We used DNA fingerprinting by random amplified polymorphic (RAPD) DNA and electrophoretic characterization of esterase isozymes to investigate the genetic relatedness of North American populations of the exotic bark beetle Tomicus piniperda (L.). Cluster analyses of genetic distances among populations identified the Illinois population as an outlier population with mean genetic distances to other populations averaging 0.895 (where complete dissimilarity = 2), compared with genetic distance averages of 0.595 among populations excluding Illinois. When genetic distance means and geographical distance between populations were compared, the results suggested that T. piniperda populations in the United States were established separately in Illinois near Lake Michigan and in Ohio along Lake Erie. Molecular markers indicated that insects derived from the 2 founder groups were interbreeding in contiguous regions in western Indiana.

Animals↗

Comparison of hematologic reference intervals between culture system and type of hybrid striped bass.

OBJECTIVE: To determine and compare hematologic reference intervals for hybrid striped bass from different culture systems and for 2 types of hybrid. DESIGN: Observational comparison study. ANIMALS: Clinically normal sunshine bass (reciprocal hybrid striped bass, female Morone chrysops X male M saxatilis) raised in high-density recirculating systems, sunshine bass raised in tanks with biofilters, and palmetto bass (original hybrid striped bass, female M saxatilis X male M chrysops) raised in tanks with biofilters. PROCEDURES: Hematologic reference intervals were determined for fish from the different production systems, following the National Committee for Clinical Laboratory Standards guidelines. Reference intervals from the 3 groups were compared. RESULTS: Reference intervals were significantly different between sunshine bass in the 2 culture systems and between sunshine and palmetto bass. Many of the differences were slight, but notable differences were observed. Sunshine bass in recirculating systems had higher total leukocyte, lymphocyte, neutrophil, and monocyte counts than did either hybrid in tanks. Palmetto bass had a greater number of neutrophils than monocytes, whereas sunshine bass had more monocytes than neutrophils. Additionally, palmetto bass had a lower PCV and hemoglobin value than did either group of sunshine bass. CONCLUSIONS: Separate reference intervals should be developed for hybrid striped bass in different culture systems and for different types of hybrids. CLINICAL RELEVANCE: Determining reference intervals for hybrid striped bass provides a tool to assess the health status of these fish.

Animals↗