Search PubMed⌕ Search

Biomedical subjects

D R Brown

Publications and source records attributed to D R Brown.

At least 55 records · Page 3Linked to original sources
PubMed2001

BSE did not cause variant CJD: an alternative cause related to post-industrial environmental contamination.

The new prion diseases that have emerged in the last 15 years are bovine spongiform encephalopathy (BSE) and variant Creutzfeldt-Jakob disease (variant CJD). Although initially confined to the UK, these diseases have recently emerged in other European countries. The accepted cause of the human disease is that BSE spread from cattle to humans by the consumption of infected beef. However, the evidence that supports this is very thin. This article describes this evidence and lists a series of hypotheses concerning the cause of both BSE and variant CJD. The final hypothesis is based on recent evidence linking prion diseases to environmental factors including manganese. High environmental availability of manganese is associated with the prevalence of those prion diseases not linked to BSE. Therefore it is quite possible that BSE and variant CJD have emerged as a result of manganese-rich industrial pollution that has only occurred in the last century.

Animals↗
PubMed2001

Major intrahepatic bile duct injuries detected after laparotomy: selective nonoperative management.

BACKGROUND: Abdominal trauma causing major intrahepatic bile duct injury is a relatively uncommon occurrence. Most authorities recommend operative, usually resectional, management of these injuries when recognized, citing increased risks of complications and mortality with nonoperative management. However, very few data have been published to document the optimal management of these challenging injuries. METHODS: We present a series of five patients with significant hepatic injury and documented major bile duct injury managed at a single provincial trauma center. All of these patients had first- or second-order bile duct injuries diagnosed using endoscopic retrograde cholangiopancreatography and had developed complications caused by the ductal injury. RESULTS: In all patients, the bile duct injury and resulting complication were successfully managed by a combination of endoscopic drainage procedures and interventional radiology techniques. Average length of hospital stay for these patients was 45 days. All patients eventually attained preinjury functional status. CONCLUSION: Nonoperative techniques can be used to successfully manage selected patients and represent a reasonable alternative to operative intervention and resectional therapy, especially in the compromised patient. Extended length of stay is to be expected, but good outcomes can be achieved.

Adolescent↗
PubMed2001

Treatment of external genital warts in men using 5% imiquimod cream applied three times a week, once daily, twice daily, or three times a day.

BACKGROUND: Medical therapy for genital warts remains suboptimal. The topical interferon and cytokine inducer, imiquimod, has been proved effective for the treatment of external genital and perianal warts, but there is a substantial difference in the response rates between men and women. When 5% imiquimod cream is applied three times a week up to 16 weeks, approximately two thirds of women treated with imiquimod achieve complete clearance of genital warts, whereas only about one third of men clear completely. GOAL: This study was undertaken to determine whether more frequent application of topical imiquimod cream would improve the rate of genital wart clearance in men. STUDY DESIGN: A randomized treatment trial involving adult men with biopsy-proven genital warts was conducted at nine centers in the United States and Canada using four different application frequencies. RESULTS: Complete clearance rates during the 16-week treatment period were as follows for the different imiquimod treatment frequencies: three times a week (35 %), once daily (28 %), twice daily (24%), and three times a day (27%)(P = 0.88). The four treatment groups all showed comparable reductions in the total lesion area, with a median of more than a 90% reduction in the lesion area by the end of treatment. There was a significant increase in the incidence and severity of local skin reactions including erythema, vesicle formation, ulceration, and excoriation as the dosing frequency increased from three times a week to three times a day. CONCLUSIONS: In this study, the optimal dosage regimen was the approved three times a week regimen. More frequent application (up to three times a day) did not improve clearance and was associated with an increase in local adverse events.

Adult↗
PubMed2001

Mycoplasma agassizii sp. nov., isolated from the upper respiratory tract of the desert tortoise (Gopherus agassizii) and the gopher tortoise (Gopherus polyphemus).

Biochemical, serological and molecular genetic studies were performed on seven mycoplasma isolates that were recovered from the upper respiratory tract of clinically ill desert tortoises. The isolates were serologically related to each other but serologically distinct from previously described species. Unique mycoplasma species-specific 16S rRNA nucleotide sequences were found in the proposed type strain. The name Mycoplasma agassizii is proposed for these isolates. The type strain is PS6T (= ATCC 700616T) which caused upper respiratory tract disease (URTD) in experimentally infected tortoises.

Animals↗
PubMed2001

Mycoplasma alligatoris sp. nov., from American alligators.

Mycoplasmas were isolated from multiple tissues of diseased American alligators (Alligator mississippiensis). This paper presents biochemical, serological and molecular genetic characterizations of a lethal pathogen of alligators for which the name Mycoplasma alligatoris sp. nov. is proposed. The type strain is A21JP2T (ATCC 700619T).

Alligators and Crocodiles↗
PubMed2001

Detection of antibodies to a pathogenic mycoplasma in American alligators (Alligator mississippiensis), broad-nosed Caimans (Caiman latirostris), and Siamese crocodiles (Crocodylus siamensis).

An epidemic of pneumonia with fibrinous polyserositis and multifocal arthritis emerged in captive American alligators (Alligator mississippiensis) in Florida, United States, in 1995. Mycoplasma alligatoris sp. nov. was cultured from multiple organs, peripheral blood, synovial fluid, and cerebrospinal fluid of affected alligators. In a subsequent experimental inoculation study, the Henle-Koch-Evans postulates were fulfilled for M. alligatoris as the etiological agent of fatal mycoplasmosis of alligators. That finding was remarkable because mycoplasmal disease is rarely fatal in animals. An enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies produced by alligators in response to M. alligatoris exposure was developed by using plasma obtained from naturally infected alligators during the original epidemic. The assay was validated by using plasma obtained during an experimental dose-response study and applied to analyze plasma obtained from captive and wild crocodilian species. The ELISA reliably detected alligator seroconversion (P < 0.05) beginning 6 weeks after inoculation. The ELISA also detected seroconversion (P < 0.05) in the relatively closely related broad-nosed caiman Caiman latirostris and the relatively distantly related Siamese crocodile Crocodylus siamensis following experimental inoculation with M. alligatoris. The ELISA may be used to monitor exposure to the lethal pathogen M. alligatoris among captive, repatriated, and wild crocodilian species.

Alligators and Crocodiles↗
PubMed2001

Detection of antibodies to a disease-associated herpesvirus of the green turtle, Chelonia mydas.

Lung-eye-trachea disease-associated herpesvirus (LETV) is linked with morbidity and mortality in mariculture-reared green turtles, but its prevalence among and impact on wild marine turtle populations is unknown. An enzyme-linked immunosorbent assay (ELISA) was developed for detection of anti-LETV antibodies and could distinguish LETV-exposed green turtles from those with antibodies to fibropapillomatosis-associated herpesvirus (FPHV). Plasma from two captive-reared green turtles immunized with inactivated LETV served as positive controls. Plasma from 42 healthy captive-reared green turtles and plasma from 30 captive-reared green turtles with experimentally induced fibropapillomatosis (FP) and anti-FPHV antibodies had low ELISA values on LETV antigen. A survey of 19 wild green turtles with and 27 without FP (with and without anti-FPHV antibodies, respectively) identified individuals with antibodies to LETV regardless of their FP status. The seroprevalence of LETV infection was 13%. The presence of antibodies to LETV in plasma samples was confirmed by Western blot and immunohistochemical analyses. These results are the first to suggest that wild Florida green turtles are exposed to LETV or to an antigenically closely related herpesvirus(es) other than FPHV and that FPHV and LETV infections are most likely independent events. This is the first ELISA developed to detect antibodies for a specific herpesvirus infection of marine turtles. The specificity of this ELISA for LETV (ability to distinguish LETV from FPHV) makes it valuable for detecting exposure to this specific herpesvirus and enhances our ability to conduct seroepidemiological studies of these disease-associated agents in marine turtles.

Animals↗
PubMed2001

Weight loss is not associated with hyperleptinemia in humans with pancreatic cancer.

Pathological weight loss is a feature of many diseases and contributes to mortality and morbidity. Although cytokines have been implicated in some models of pathological weight loss, little is known about cellular mechanisms responsible for cachexia in patients with cancer. Leptin is a fat cell product that acts centrally to reduce appetite and decrease metabolism. Leptin synthesis is stimulated by cytokines, and circulating levels of cytokines are elevated in some cancer patients. We hypothesized that cytokine-induced hyperleptinemia contributes to pathological weight loss in patients with pancreatic cancer. To evaluate this hypothesis, fasting serum leptin concentrations were measured in 64 patients undergoing surgery for pancreatic cancer. Preoperative interviews were used to assess body weight and appetite history. Thirty of 64 pancreatic cancer patients had cachexia (weight loss of >10% over the 6 months before surgery). Self-reported loss of appetite was associated with the presence of cachexia. Leptin concentrations, when corrected for body mass index, were lower than levels reported in healthy humans. Six patients had leptin levels more than 2 times those predicted by body mass index. There was no association between patients with increased leptin concentration and weight loss or anorexia. We conclude that a reduced appetite contributes to weight loss in patients with pancreatic cancer. High plasma leptin levels, however, do not appear to contribute to cachexia in these patients.

Aged↗
PubMed2001

Experimental inoculation of broad-nosed caimans (Caiman latirostris) and Siamese crocodiles (Crocodylus siamensis) with Mycoplasma alligatoris.

An outbreak of mycoplasmosis caused by Mycoplasma alligatoris resulted in the death or euthanasia of 60 American alligators (Alligator mississippiensis) from a population of 74 captive bull alligators in Florida in 1995. The natural reservoir, routes of transmission, and host range of M. alligatoris are unknown. This study was undertaken to determine whether crocodilian species other than American alligators are susceptible to M. alligatoris. Six broad-nosed caimans (Caiman latirostris) and six Siamese crocodiles (Crocodylus siamensis) were experimentally inoculated with 10(6) colony forming units (CFU) of M. alligatoris instilled through the glottis. Two caimans and two crocodiles were used as negative controls. Six and four American alligators were used as positive and negative controls, respectively. Three of six (50%) inoculated caimans died within 10 wk postinoculation (PI) of severe mycoplasmosis. Gross necropsy, histopathologic, and culture results were similar for broad-nosed caimans and American alligators. None of the inoculated Siamese crocodiles developed mycoplasmosis, though M. alligatoris was isolated from the tonsils in three of six (50%) animals at necropsy. All the inoculated crocodilians that survived showed significant seroconversion by 6-8-wk PI (P < 0.05). The infective dose 50% (ID50) and lethal dose 50% (LD50) of M. alligatoris for the broad-nosed caiman are 10(6) CFU when instilled through the glottis, which is similar to that of the American alligator. Although the host range of M. alligatoris is not restricted to the American alligator, the organism does not appear to be pathogenic for Siamese crocodiles. Other species of crocodilians may be susceptible to infection with M. alligatoris, and this organism should be considered when the rapid onset of clinical signs of pneumonia, polyarthritis, pericarditis, and death occur.

Alligators and Crocodiles↗
PubMed2001

Inclusion of an intravaginal progesterone insert plus GnRH and prostaglandin F2alpha for ovulation control in postpartum suckled beef cows.

Four experiment stations (IL, KS, MN, and MO) conducted experiments to determine effects of introducing a CIDR (controlled internal device release) into an ovulation control program for postpartum suckled beef cows. Five hundred sixty cows were assigned randomly to two treatments: 1) 100 microg of GnRH (i.m.) followed in 7 d with 25 mg of PGF2alpha, followed in 48 h by a second injection of GnRH and one fixed-time insemination (Cosynch; n = 287) or 2) Cosynch plus one CIDR during the 7 d between the first injection of GnRH and PGF2alpha (Cosynch+P; n = 273). Cows at three stations were inseminated at the time of the second GnRH injection (n = 462), whereas 98 cows at the fourth station were inseminated 16 to 18 h after that injection. Blood samples were collected at d -17, -7, 0, and 2 relative to PGF2alpha to determine concentrations of progesterone. Ultrasonography was used to monitor follicle diameter on d 2 and to determine the presence of an embryo at 30 to 35 d after insemination. Pregnancy rates were greater (P < 0.05) for Cosynch+P- (58%) than for Cosynch-treated (48%) cows. No station x treatment interaction occurred; however, cows at MO (62%) and KS (60%) had greater (P < 0.05) pregnancy rates than those at IL (47%) and MN (44%). Cows that had follicles > 12 mm on d 2 had greater (P < 0.01) pregnancy rates than those with follicles < or = 12 mm regardless of treatment. Pregnancy rates were similar between Cosynch and Cosynch+P treatments when cycling cows had elevated concentrations of progesterone at d 0, but pregnancy rates were greater (P < 0.05) in the Cosynch+P (79%) than in the Cosynch (43%) treatment when cycling cows had low concentrations of progesterone on d 0 (at PGF2alpha injection). Similarly, among noncycling cows, pregnancy rates were greater (P < 0.05) in the Cosynch+P (59%) treatment than in the Cosynch (39%) treatment. Cows in greater body condition at the onset of the breeding season experienced improved (P < 0.001) overall pregnancy rates. Pregnancy rates for cows that calved > 50 d before the onset of the breeding season were greater (P < 0.01) than those for cows that calved < or = 50 d. Thus, treatment of suckled cows with Cosynch yielded acceptable pregnancy rates, but addition of a CIDR improved pregnancy rates in noncycling cows. Body condition and days postpartum at initiation of the breeding season affected overall efficacy of the Cosynch and Cosynch+P protocols.

Administration, Intravaginal↗
PubMed2001

The human oncoprotein MDM2 uses distinct strategies to inhibit transcriptional activation mediated by the wild-type p53 and its tumor-derived mutants.

Human MDM2 (hMDM2) inhibits transcriptional activation mediated by wild-type p53 and its tumor-derived mutants. We present evidence to show that hMDM2 interacts with the tumor-derived mutants of p53 and inhibits transcriptional activation of the human c-myc promoter mediated by the tumor-derived mutants of p53 through two domains. These two domains of hMDM2 are able to function independent of each other. Interaction with either of the domains is sufficient for inhibition of mutant p53-mediated transactivation. One of these domains is the same as the wild-type p53 interaction domain of hMDM2, whereas a second domain is situated within amino acid 190 and 276 residues and is specific for mutant p53. hMDM2 does not inhibit transcriptional activation mediated by the transcriptional activator VP16, suggesting that the inhibition is not mediated by inactivation of a general transcription factor. The transactivation and the oligomerization domains of mutant p53 are dispensable for its interaction with hMDM2. Thus, both hMDM2 and p53 recognize each other through unique domains. These observations suggest that forms of hMDM2 incapable of interacting with the wild-type p53, and are often expressed in transformed cells, would inhibit mutant p53-mediated transactivation and antagonize the tumorigenic function of mutant p53. This inhibitory function of hMDM2 may account for infrequent co-occurrence of p53 mutation and hMDM2 overexpression in cancer cells. Our results also suggest distinct mechanisms for wild-type and mutant p53-mediated transcriptional activation.

Biomarkers, Tumor↗
PubMed2001

Pathology of experimental mycoplasmosis in American alligators.

Mycoplasma alligatoris was the suspected etiology of an epidemic of acute multisystemic inflammatory disease which emerged in captive American alligators (Alligator mississippiensis) in Florida (USA) in 1995. In an experimental inoculation study conducted from April through October 1999, 18 alligators were inoculated with 10(2), 10(4), or 10(6) colony forming units (CFU) of M. alligatoris by instillation into the glottis. As early as 1 wk post-inoculation (PI), mycoplasma were cultured from blood of three of six alligators inoculated with 10(6) CFU. Two of those died and the third was euthanatized within 4 wk PI. Necropsy gross findings included fibrinous polyserositis and polyarthritis. Histopathologic changes in affected individuals included pulmonary edema, interstitial pneumonia, pericarditis, myocarditis, meningitis, and synovitis. Mycoplasma were cultured quantitatively in high numbers from trachea, lung, coelomic cavity, liver, spleen, interior of pericardial sac, heart, blood, brain, and limb joints. In alligators inoculated with 10(6) CFU, heterophilia and moderate hyperglycemia peaked about 4 wk PI, and seroconversion occurred by 6 to 8 wk PI. Necropsy gross and histologic findings were generally unremarkable for the surviving alligators inoculated with 10(6) CFU, alligators inoculated with 10(2) or 10(4) CFU, and four uninoculated control alligators. Mycoplasma were not cultured at any time point from those alligators. The findings confirm that M. alligatoris can cause fulminant inflammatory disease and rapid death of alligators.

Acute Disease↗
PubMed2001

Differential modulation of cellular and viral promoters by p73 and p53.

p73 has been shown to transcriptionally activate genes positively responsive to wild-type p53. In order to undertake a comparative study of functions of p53 and p73 we have cloned the cDNA of p73 from MCF-7 cells. Adenovirus onco-protein E1A inhibits the transactivation by p73; a deletion mutant of E1A incapable of interacting with p300 and CREB-binding protein (CBP) fails to disrupt the transactivation. Furthermore, CBP increases the transactivation mediated by p73 suggesting that CBP may function as a co-activator and E1A inhibits p73-mediated transactivation by sequestering p300 or CBP. We show that p73 can transcriptionally inhibit a number of cellular and viral promoters. However, wild-type p53, p73 alpha and p73 beta differ in their ability to inhibit transcriptional activity of different promoters. While wild-type p53 inhibits the promoters of the human cytomegalovirus (CMV) immediate-early gene, the long terminal repeat of human immunodeficiency virus type 1 (HIV LTR), human cyclin A (cyc A) gene, and insulin-like growth factor receptor I (IGF-I-R), p73 alpha only inhibits the HIV LTR and cyc A promoters significantly; and p73 beta inhibits the CMV, HIV LTR and cyc A promoters. A mutant of p73 alpha having amino acid substitutions at positions 268 and 300 on the presumptive DNA-binding domain fails to transactivate the p21 promoter but represses the CMV and the HIV LTR promoter quite efficiently showing that the mechanisms of transactivation and repression by p73 are different. Interestingly, p73 alpha transactivates the IGF-I-R promoter, which is inhibited by wild-type p53; p73 beta has no significant effect on this promoter. This is a unique situation where p73 alpha differs from p73 beta as well as p53.

Adenovirus E1A Proteins↗
PubMed2001

Characterization of opioid receptors modulating neurogenic contractions of circular muscle from porcine ileum and evidence that delta- and kappa-opioid receptors are coexpressed in myenteric neurons.

Opioid receptors (ORs) in the myenteric plexus mediate the antimotility actions of opioids in the small intestine. In this study, ORs modulating neurogenic circular muscle contractions in the porcine ileum were characterized by pharmacological and immunohistochemical approaches. Circular muscle-myenteric plexus strips manifested tetrodotoxin- and atropine-sensitive contractions during (ON) and after (OFF) electrical field stimulation. The kappa-OR agonists U-50,488H and U-69,593 inhibited ON contractions (pIC(50) = 7.61 and 8.22, respectively). U-69,593 action was inhibited by the kappa-OR antagonist norbinaltorphimine with an antagonist equilibrium constant (K(e)) of 4.2 nM. Selective delta-OR agonists [D-Ala(2)]-deltorphin II, DSLET, DADLE, SNC80, and DPDPE inhibited OFF contractions (pIC(50) = 9.17, 8.63, 8.50, 8.26, and 7.47, respectively). The selective delta-OR antagonist naltriben reduced the inhibitory actions of SNC80 and DSLET with respective K(e) values of 2.3 and 3.0 nM. In addition, norbinaltorphimine inhibited the actions of these agonists with respective K(e) values of 0.7 and 4.2 nM. The mu-OR agonists DAMGO, loperamide, or morphine exhibited relatively low activities in inhibiting ON and OFF contractions. Using primary antisera directed toward cloned opioid receptors, delta-OR immunoreactivity was observed to be localized alone or in combination with kappa-OR immunoreactivity in myenteric neurons; mu-OR immunoreactivity was absent. The results suggest that myenteric delta- and kappa-opioid receptors mediate the antitransit effects of opioids in the porcine small intestine. These receptors may be functionally coupled in a subpopulation of myenteric neurons.

Amino Acid Sequence↗
PubMed2001

Pharmacological evidence for a 7-benzylidenenaltrexone-preferring opioid receptor mediating the inhibitory actions of peptidic delta- and mu-opioid agonists on neurogenic ion transport in porcine ileal mucosa.

The antidiarrheal and constipating effects of opiates are partly attributed to reductions in active anion secretion across the intestinal mucosa that are modulated by submucosal neurons. In this study, the opioid receptor mediating the actions of opioids on ion transport was characterized in mucosa-submucosa sheets from porcine ileum. Electrical transmural stimulation evoked transient increases in short-circuit current, an electrical measure of neurogenic ion transport, in this preparation. After serosal addition, the peptidic delta-opioid agonists [D-Ala(2)]-deltorphin II (pIC(50) = 8.4 +/- 0.7), [D-Ala(2),D-Leu(5)]-enkephalin (DADLE), [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE), and [D-Ser(2),Leu(5),Thr(6)]-enkephalin (DSLET), and the mu-opioid agonists [D-Ala(2),N-methyl-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) (pIC(50) = 8.0 +/- 0.1), endomorphin I, and PL-017 inhibited short-circuit current elevations. Nonpeptidic mu- or delta-opioid agonists (morphine, loperamide, and SNC80) and kappa-opioid agonists (U-50,488H and U-69,593) were <360-fold less potent than deltorphin II. At 100 nM, the delta(1)-opioid antagonist 7-benzylidenenaltrexone reduced the potencies of DPDPE and DAMGO by 13.5- and 15.5-fold, respectively; at an identical concentration naltriben, a delta(2)-opioid antagonist, or the mu-opioid antagonist D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP) reduced DPDPE potency by 4.1- and 3.4-fold, respectively, but had no significant effect on DAMGO potency. Using primary antisera directed toward cloned opioid receptors, delta-opioid receptor immunoreactivity was immunohistochemically localized in submucosal neurons and nerve fibers, but immunoreactivities to kappa- or mu-opioid receptors were not detected in the mucosa-submucosa. These results suggest that a novel 7-benzylidenenaltrexone-sensitive opioid receptor is expressed in submucosal neurons of the porcine ileum, which mediates the inhibitory effects of peptidic mu- and delta-opioid agonists on neurogenic ion transport.

Animals↗