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Biomedical subjects

B J Smith

Publications and source records attributed to B J Smith.

At least 145 records · Page 8Linked to original sources

Fine structure of the pecten oculi of the barred owl (Strix varia).

The pecten oculi of the barred owl (Strix varia) has been examined by light and transmission electron microscopy. The pecten in this species is of the pleated type and is small in comparison to the size of the ocular globe. The pecten consists of 8-10 accordion-like folds that are linked apically by a pigmented tissue bridge. Each fold contains numerous capillaries, larger supply and drainage vessels, and abundant pleomorphic melanocytes. Most of these capillaries are extremely specialized vessels that possess plentiful microfolds on both the luminal and abluminal surfaces. Some capillaries however display only a few microfolds. The endothelial cell bodies are extremely attenuated, with most organelles located near the nucleus. All capillaries are surrounded by a very thick fibrillar basal lamina, which is thought to provide structural support to these small vessels. Pericytes are commonly found within these thickened basal laminae. Numerous melanocytes are also present, with processes that form an incomplete sheath around the capillaries. These processes are also presumed to provide structural support for the capillaries. As in other avian species, the morphology of the barred owl pecten is indicative of extensive involvement in substance transport. When compared to the pecten of more visually-oriented species, this pecten is smaller, has fewer folds, and displays a reduced number of microfolds within the capillaries. In these and other features, the barred owl pecten is similar to the pecten of the great horned owl (Bubo virginianus).

Animals↗

Characterization of the effects of tebufelone on hepatic cytochromes P450 in the beagle dog.

Tebufelone (1-[3,5-bis(1,1-dimethylethyl)-4-hydroxy-phenyl]-hex-5-yne-1-one) is an investigational ditertiary butylphenol nonsteroidal anti-inflammatory drug. The purpose of the present study was to assess the effects of tebufelone on hepatocyte ultrastructure and hepatic cytochromes p450 (P450s) in the beagle dog after 2 weeks of oral administration at dose levels of 0, 5, 15, 50, and 100 mg/kg/day (N = 1/sex/dose level). Hepatic tissue was obtained at necropsy for histologic, ultrastructural, and biochemical evaluation. Hepatocellular hypertrophy was observed in only a single tebufelone-treated dog (50 mg/kg). Electron microscopic evaluation, however, revealed marked dose-dependent increases in smooth endoplasmic reticulum in all of the tebufelone treatment groups. Biochemical indicators suggested that tebufelone produced mixed effects on hepatic P450s. p-Nitroanisole O-demethylase and, to a greater extent, ethoxyresorufin O-deethylase activities were decreased with increasing tebufelone dose. The precise mechanism by which tebufelone decreased ethoxyresorufin O-deethylase activity in dogs in unknown, but it was not by competitive inhibition, P450 inactivation, or reduced CYP1A expression. Tebufelone treatment increased NADPH-dependent cytochrome c reductase, total P450, and indicators of CYP2B11 (chloramphenicol covalent binding and immunochemically determined 2B11) and CYP3A12 (erythromycin N-demethylase, triacetyloleandomycin spectral complex formation, testosterone 6 beta-hydroxylase, and immunochemically determined 3A12). The largest increase in the 2B11 and 3A12 markers occurred in the 50 or 100 mg/kg treatment groups. The greatest increase in CYP2B11 markers produced by tebufelone treatment ranged from 2- to 3-fold, whereas the increase in CYP3A12 markers ranged from 5- to 10-fold. The changes in hepatic ultrastructure and increases in CYP2B11 and CYP3A12 markers produced by tebufelone in dogs are similar to that reported for phenobarbital.

Alkynes↗

Patella of selected bats: patterns of occurrence or absence and associated modifications of the quadriceps femoris tendon.

BACKGROUND: Having observed the apparent absence of a bony patella in a Madagascar flying fox (Pteropus sp.), other species from the two suborders of bats (Megachiroptera and Microchiroptera) were examined to determine the presence or absence of a bony patella and the distribution of this feature among bats. METHODS: Gross, radiographic, and histologic examination of seven megachiropteran species representing four genera, as well as six microchiropteran species representing six genera, was performed. RESULTS: A bony patella was observed in all six microchiropteran and in three megachiropteran species. The tendon of the quadriceps femoris muscle in Microchiropteran species was composed mainly of dense regular connective tissue. The quadriceps tendon in Megachiropteran species with a patella contained an abundance of fibrocartilage and hyaline cartilage, unlike the quadriceps femoris tendon of the Microchiroptera or a laboratory mouse examined for comparison. CONCLUSIONS: Four species of the megachiropteran genus Pteropus lacking a bony patella displayed a similar occurrence and distribution of fibrocartilage and hyaline cartilage within the quadriceps tendon as seen in the other bats. In reference to this singular feature, Pteropus is unique among the representatives of megachiropteran and microchiropteran genera examined here.

Animals↗

Alterations in murine fetal thymus and liver hematopoietic cell populations following developmental exposure to 7,12-dimethylbenz[a]anthracene.

Gestational exposure of ICR mice to the environmental contaminant 7,12-dimethylbenz[a]anthracene (DMBA) was used (i) to study the developmental immunotoxicity of this chemical agent and (ii) to evaluate potential hematopoietic cellular targets in a sensitive developmental model which may be involved in immunosuppression induced by this carcinogenic polycyclic aromatic hydrocarbon (PAH). DMBA produced a dose-dependent hypocellularity in both fetal mouse thymus and liver. Resident hematopoietic cell subpopulations in fetal liver, identified by CD44, CD45R, and Mac-1 monoclonal antibody binding, were reduced by the gestational DMBA treatment. In particular, the total number of CD45R+ B-lineage lymphocytic cells in fetal liver was reduced to 20% of control levels by DMBA. Unlike previous reports with related PAH, DMBA did not inhibit thymocyte differentiation, as indicated by unaltered thymocyte expression of CD4, CD8, and heat-stable antigens. These data may indicate that production of thymic atrophy and impairment of thymocyte differentiation by PAH involve separate mechanisms of action. Results of the present study additionally identify changes in immune cell populations that correlate well with inhibition of cell- and humoral-mediated immunity in experimental animals treated with DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

B lymphocyte precursor cells represent sensitive targets of T2 mycotoxin exposure.

Exposure of experimental animals and humans to the Fusarium trichothecene metabolite, T2 toxin, has been associated with a variety of immunosuppressive effects, including altered parameters of humoral-mediated immunity. Although T2 toxin is cytotoxic in vitro to lymphocytic cells, limited information is presently available regarding the contribution of such a mechanism to immunosuppression in vivo, or to potential immune cell targets. In the present report, subchronic T2 toxin treatment of timed-pregnant B6C3F1 mice resulted in significant and selective depletion of fetal liver cells expressing low levels of surface CD44 and CD45 antigens, suggestive of possible lymphoid progenitor cell sensitivity to this agent. Evaluation of CD45R antigen expression in fetal liver supported such a hypothesis, demonstrating a significant reduction in fetal liver B lymphocytic cells in animals exposed to T2 toxin. Subsequent in vitro T2 toxin exposure of fetal liver cells enriched for prolymphocytes by differential density gradient centrifugation demonstrated the presence of a highly sensitive subpopulation of cells that was eliminated in a selective, and near-complete, manner by T2 toxin exposure. This sensitive cell population was observed to have light-scatter characteristics of CD45R+ B-lineage lymphocytes. Additional studies in adult mice demonstrated a reduction in CD44lo and CD45R+ bone marrow cells similar to that seen in fetal liver, indicating that T2 toxin may also target immature B lymphocytes in this hematopoietic compartment. Taken together, these data suggest that the precursors of B cells may represent, for unknown reasons, highly sensitive targets of T2 toxin exposure.

Animals↗

Prevalence and serovars of leptospira involved in equine abortions in central Kentucky during the 1991-1993 foaling seasons.

In this study, the prevalence of leptospira-induced abortions/stillbirths for the past 3 foaling seasons (1991-1993) was determined, and fetal tissues and/or the mare's urine from positive cases were cultured in an attempt to isolate and identify the leptospira serovars responsible for the abortions. The sensitivity and specificity of the primary diagnostic tests, the fluorescent antibody test (FAT) and the microscopic agglutination test (MAT), used for the diagnosis of leptospirosis were also determined. For the 3 years, 74 (3.3%) of 2,264 abortion/stillborn submissions were diagnosed as leptospirosis. Twelve cases occurred in the 1991, 19 in the 1992, and 43 in the 1993 foaling seasons. Leptospires were isolated from 45 (60.8%) of the 74 cases, and they were identified as serovar kennewicki (43 cases), serovar grippotyphosa (1 case), and a serovar similar to pomona (1 case). Of the 29 culture-negative cases, serologic results indicated that leptospires in the Pomona serogroup (kennewicki is a member of this serogroup) were responsible for 25 abortions, leptospires in the Grippotyphosa serogroup for 1 abortion, and leptospires in the Sejroe serogroup for 1 abortion. The specificities of the FAT on fetal tissues and mare's placenta and of the MAT on fetal fluid were 100%. The sensitivity of the FAT was 98.7%, and that of the MAT was 81.3%.

Abortion, Veterinary↗

Exploring widows' experiences after the suicide of their spouse.

1. The widow of a spouse who committed suicide must cope with issues related to depression, anger, blame, guilt, and the stigma associated with suicide that makes recovery from this type of loss different for the survivors. 2. The predominant need of widows and widowers of suicide victims was to talk in an environment of acceptance and understanding, which could only be provided by other people who have had the same kind of experience. 3. There is no precise formula that exists to guide caregivers when assisting survivors of suicide victims, however suggestions include communicating with compassion; demonstrating care and concern; accepting the individual's grief; and offering and providing information.

Adaptation, Psychological↗

Benzo[a]pyrene-induced alterations in total immune cell number and cell-surface antigen expression in the thymus, spleen and bone marrow of B6C3F1 mice.

Although considerable evidence suggests that carcinogenic polycyclic aromatic hydrocarbons are immunosuppressive compounds, limited information is available regarding precise effects of these agents on immune cells. In the present report, the effect of subchronic exposure to benzo[a]pyrene (B[a]P) on immune cells in bone marrow, thymus and spleen of B6C3F1 mice was investigated. B[a]P treatment was found to reduce thymic cellularity and also to significantly alter normal thymocyte differentiation, as indicated by expression of CD4 and CD8 cell-surface antigens. Exposure to B[a]P also reduced cellularity of the bone marrow, including decreased percentage and absolute number of CD45R+ B-lineage lymphocytes. Further, B[a]P treatment dramatically increased the percentage of CD44hi cells in bone marrow, while proportionately reducing CD44lo cells. These results may indicate CD44lo bone marrow cells, including prolymphocytic cells, represent sensitive targets of B[a]P. The spleens of treated mice were found deficient in both Thy 1.2+ T lymphocytes and CD45R+ B lymphocytes, effects that correlate well with the chemical-induced alterations observed in thymus and bone marrow, respectively.

Animals↗

Reciprocated matrix metalloproteinase activation: a process performed by interstitial collagenase and progelatinase A.

Gelatinase A, a member of the matrix metalloproteinase (MMP) family, is secreted possessing an 80 amino acid N-terminal propeptide that must be removed in order to generate the active enzyme. Purified progelatinase A was activated to 38% of maximum by a 6 h incubation at 37 degrees C with equimolar concentrations of trypsin-activated interstitial collagenase (another MMP). The increase in activity was accompanied by cleavage of the M(r) 72,000 progelatinase A to the M(r) 66,000 active enzyme that has Y81 as its N-terminus. At low concentrations, progelatinase A was processed via an inactive intermediate, suggesting that its activation is a biphasic process. This was confirmed by the action of collagenase on proE375-->A (a mutant of progelatinase A that cannot become active) because, in this instance, only an M(r) 68,000 species with L38 as the N-terminus was produced. The remaining propeptide amino acids to Y81 could be readily removed by added active gelatinase A, indicating that collagenase works by generating an intermediate that is susceptible to autolytic activation. Although relatively slow, the rate of activation could be increased approximately 10-fold by the addition of 100 micrograms/mL heparin. This binds to the C-terminal domain of collagenase and progelatinase A and presumably acts as a template that positions the reactants close to one another. Collagenase activated by trypsin retains 8 or 14 amino acids of its propeptide.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

The univin gene encodes a member of the transforming growth factor-beta superfamily with restricted expression in the sea urchin embryo.

We have identified a gene in the sea urchin Strongylocentrotus purpuratus that encodes a member of the transforming growth factor beta (TGF-beta) gene superfamily. We have named the gene univin, and it is the first member of this superfamily to be reported in echinoderms. The cDNA sequence predicts a 383-amino-acid residue protein with 7 cysteine residues characteristic of members of this superfamily and with a cluster of basic residues appropriately situated to signal proteolytic cleavage. Sequence comparisons place univin in the bone morphogenetic protein (BMP) group of the TGF-beta superfamily along with the vertebrate BMPs, decapentaplegic protein from Drosophila, and Vg-1 from Xenopus. Analyses of univin expression in early embryos by RNA blots and in situ hybridization revealed the highest levels of expression in the egg and prehatching blastula. During late cleavage stages, univin mRNA accumulation is progressively restricted to a circumequatorial band. Expression is further restricted during gastrulation when univin transcripts are detected primarily in the presumptive foregut and ciliated band. By pluteus stage, signals are detectable only in these cell types. The restricted temporal and spatial patterns of expression of univin during early blastula stages parallel those of SpAN, which encodes an astacin-like protease related to tolloid and BMP-1 (Reynolds et al., 1992). The fact that these proteases are thought to function in the proteolytic activation of TGF-beta-related proteins that, respectively, regulate Drosophila embryonic dorsal-ventral patterning and vertebrate bone development suggests that SpAN and univin could also have critical roles in early developmental decisions in the sea urchin embryo.

Amino Acid Sequence↗

A new technique for handling sexually abusive calls to telephone crisis lines.

Sexually abusive calls interfere with the legitimate functions of crisis lines and have detrimental effects on crisis line workers. This paper describes a new approach to responding to such calls in a way that meets the needs of the crisis line and encourages callers to seek therapeutic treatment for their problem. The proposed response is based on principles of covert conditioning and Ericksonian suggestions. A script of the response is presented along with a description of the rationale and suggested precautions for use with callers.

Female↗

Hematopoietic alterations after exposure to T-2 mycotoxin.

Adult mice were exposed by oral gavage to 0.75, 1.25, or 1.75 mg/kg body weight T-2 mycotoxin for 5 consecutive days. Thymic atrophy on the 2nd day following cessation of dosing was profound, and was characterized by significant decreases in the total number of cells within all phenotypes defined by CD4 and CD8 cell-surface antigen expression. Further, the distribution of thymocytes within these phenotypes was significantly altered. Increased percentages of CD4-8- (DN) and decreased percentages of CD4+8+ (DP) cells in thymuses from treated animals suggested that T-2 toxin may inhibit thymocyte maturation. In addition to thymus, the bone marrow of treated animals showed a highly significant hypocellularity, indicating that this hematopoietic compartment may also be targeted by T-2 toxin. A trend toward reduced splenic cellularity was additionally observed in exposed animals, but failed to reach significance. A significant decrease in the total number of both B and T-lymphocytes present within the spleen was observed, however. These data, taken together, indicate that effects at multiple hematopoietic compartments involved in the production of T-lymphocytes may contribute to the peripheral T-cell lymphocytopenia and T-cell mediated immunosuppression produced by T-2 toxin.

Administration, Oral↗

Healing of implant dehiscence defects with and without expanded polytetrafluoroethylene membranes: a controlled clinical and histological study.

Bone augmentation around implant fixtures using the technique of guided tissue regeneration has been described in a number of reports. The aim of this study was to evaluate bone fill around dehiscence defects at matched defects randomly allocated to test (expanded polytetrafluoroethylene; Gore-Tex) or control treatments within the same patient. Six edentulous subjects were treated with overdentures supported by 2 fixtures ad modum Bränemark. In addition, 2 experimental 7-mm fixtures with nearly identical dehiscence defects on the labial aspect were placed in the anterior part of the mandible. Baseline defect heights ranged from 2.5 to 4.0 mm with 2 to 4 threads exposed. The test fixture dehiscence was covered with a Gore-Tex membrane secured with a cover screw. The experimental fixtures were exposed after 5 months at stage 2 surgery and measurements and photographs repeated. The fixtures were then removed with a trephine and processed for histological evaluation. Regeneration of a hard tissue resembling bone was observed in 4 of 6 cases treated with Gore-Tex, amounting to between 95 and 100% elimination of the dehiscence and total coverage of the threads. However, in one of these cases, histological evaluation showed that it was soft tissue and not bone, and in a further case soft tissue regeneration was apparent both clinically and histologically. In another case there was no significant regeneration at either test or control defects. Although there was a trend for the Gore-Tex-treated dehiscences to respond more favourably, the differences in clinical and histological measurements between test and control failed to reach statistical significance.

Adult↗

Fetal hematopoietic alterations after maternal exposure to benzo[a]pyrene: a cytometric evaluation.

In utero exposure to the environmental contaminant benzo[a]pyrene (BaP) was found to alter expression of murine thymocyte and liver fetal cell-surface markers. Pregnant mice were treated (via gavage) with 0, 50, 100, or 150 mg BaP/kg/d on gestational days (gd) 13-17, and offspring were examined on gd 18. Severe thymic atrophy and cellular depletion were found in BaP-exposed fetal mice. Flow cytometric analysis indicated that the BaP treatment resulted in a significant decrease in the percentage of CD4+8+ fetal thymocytes, as well as significantly increased CD4-8- and CD4-8+ thymocytes. Staining of thymocytes with anti-mouse heat-stable antigen (HSA) and CD8 monoclonal antibodies produced similar results. These data suggest that BaP, in addition to producing thymic hypocellularity, inhibits normal thymocyte maturation processes. The BaP treatment was also found to decrease total fetal liver cellularity including numbers of cells within resident hematopoietic subpopulations. In particular, prolymphocytic cells, identified by CD44 and CD45R antigen expression and by presence of nuclear terminal deoxynucleotidyl transferase (TdT), were significantly decreased in animals gestationally exposed to BaP. These data, taken together, indicate that postnatal suppression of cell and humoral-mediated immune function following in utero exposure to BaP may result from multiple targeting of immune cells at different hematopoietic levels. Furthermore, results of the present study identify both qualitative and quantitative changes in fetal immune cell antigen expression that correlate well with the postnatal immunosuppression that occurs in experimental animals exposed to this carcinogenic polycyclic aromatic hydrocarbon.

Animals↗

Does beclomethasone dipropionate suppress dehydroepiandrosterone sulphate in postmenopausal women?

BACKGROUND: Patients with chronic obstructive airways disease and asthma are at special risk of developing osteoporosis. Previous research has indicated that adrenal androgen levels in postmenopausal women are suppressed by short term high dose inhaled corticosteroids. Such an effect, if sustained, may be a causative factor for long term bone loss. We tested the hypothesis that postmenopausal women receiving > or = 1 mg/day inhaled beclomethasone dipropionate, long term, have suppressed dehydroepiandrosterone sulphate levels when compared to postmenopausal controls. METHODS: As part of a larger study, we studied 36 postmenopausal subjects, recruited from regional pharmacies and a hospital chest clinic, who had been receiving treatment for asthma. Subjects were selected if they were receiving > or = 1 mg/day inhaled beclomethasone dipropionate (n = 27) or receiving no beclomethasone dipropionate (n = 9). The two groups were compared for dehydroepiandrosterone sulphate levels, age and potential confounders. RESULTS: Mean dehydroepiandrosterone sulphate levels were 35% lower in the high dose beclomethasone dipropionate group than the control group (p < 0.01). CONCLUSIONS: This is the first report of suppression of dehydroepiandrosterone sulphate in postmenopausal women receiving long term inhaled beclomethasone dipropionate. Further research is needed to clarify whether or not there is any associated clinically important adverse effect on bone density.

Age Distribution↗

Serological and microbiological findings on 3 farms with equine leptospiral abortions.

Blood and urine samples from horses on 3 central Kentucky horse farms with prior histories of leptospiral abortions were analysed. Blood samples were obtained from all available horses on each farm and tested for antibodies to 6 leptospira serovars. Urine samples were collected from non-gravid mares with serum antibody titres > or = 1:800 and examined for leptospires by dark-field microscopy, fluorescent antibody testing and culture. Adult horses had the greatest serological evidence of exposure to leptospira, followed by yearlings, then foals. Of horses with anti-leptospiral antibodies, 76.3% reacted against serovar bratislava, 49.1% against icterohaemorrhagiae, 20.1% against grippotyphosa, 16.3% against pomona genotype kennewicki, 15.9% against hardjo and 1.0% against canicola. These findings confirmed that horses in central Kentucky are exposed to multiple leptospira serovars. The seroprevalence of antibodies to the 6 selected serovars was consistent among the 3 selected farms. There was no direct correlation between the serovar that was the cause of abortion in the previous season and prevalence of positive titres to that serovar in horses tested on the farms in the following year. Furthermore, there was no evidence of long-term urinary shedding of leptospira by horses with high leptospira antibody titres.

Abortion, Veterinary↗