Behavioural and cortisol response of pigs and sheep during transport.
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Animals↗
Biomedical subjects
S J Hall
Publications and source records attributed to S J Hall.
Prostate cancer gene therapy: herpes simplex virus thymidine kinase gene transduction followed by ganciclovir in mouse and human prostate cancer models.
Prostate cancer is the most common internal malignancy in men in the United States. Most cancers are diagnosed when they are locally advanced or metastatic and there is no effective treatment. In this study we evaluated the effectiveness of cytotoxic gene therapy in human PC-3 and DU145 prostate cancer cell lines and in a rodent cell line, RM-1, derived from the mouse prostate reconstitution model system. The cell lines were efficiently transduced in vitro by a replicative-defective recombinant adenovirus (ADV) carrying the herpes simplex virus thymidine kinase gene (HSV-tk). A virus titer-dependent sensitivity to ganciclovir (GCV) was observed. To determine a target therapeutic viral dose in vivo, subcutaneous tumors were generated by injection of RM-1 cells in syngeneic male hosts and injected with escalating doses of HSV-tk virus (5 x 10(7) to 1 x 10(9) pfu). The mice received GCV twice daily for 6 days and were sacrificed when tumor volumes exceeded 2.5 cm3 or when they appeared to be in distress. Because the two highest doses were equally as effective, further controlled studies were performed with the lower dose of 5 x 10(8) pfu with ADV/RSV-tk or a control virus containing the beta-galactosidase gene (ADV/RSV-beta-Gal) and treated with GCV or saline (PBS). The mean tumor volume in the treated animals was 16% that of control animals at 13 days. Histologically, treated tumors demonstrated necrosis and had a significantly higher apoptotic index. Survival data indicated that the treatment animals lived 7 days (21 in total) longer than the control animals, with 1 treatment animal being totally free of tumor. These results demonstrate that HSV-tk + GCV cytotoxic gene therapy can inhibit the growth of mouse and human prostate cancer cells in vitro and interrupt tumor growth of an aggressive mouse prostate cancer cell line in vivo.
Adenoviridae↗
Hormonal and physiological effects of a 15 hour road journey in sheep: comparison with the responses to loading, handling and penning in the absence of transport.
A controlled study was carried out to investigate the physiological effects of road transport on sheep. Animals (n = 10; body weight 38.9 +/- 1.3 kg), previously with catheters in their jugular veins, were rounded up and loaded onto a vehicle where they were held in a communal pen with eight other lambs. Blood samples were taken at 30 min intervals during the next 15 h while the vehicle remained stationary or was driven a distance of 548 miles (876 km). Measurements were made of plasma concentrations of cortisol, prolactin, creatine phosphokinase and lactase dehydrogenase isozymes and also of plasma osmolality, haematocrit and body weight; heart rate was also recorded in one animal. Loading and the start of driving produced large increases in cortisol and prolactin concentrations. Heart rate also increased whereas osmolality and haematocrit decreased. The major changes in hormone release occurred in the first 3 h period while, during the remaining 12 h, the stimulatory effect of transport was present but small. Body weight loss was similar under both stationary and driven conditions.
Animal Welfare↗
In vivo gene therapy with p53 or p21 adenovirus for prostate cancer.
We introduced the gene for wild-type human p53 or p21, a critical downstream mediator of p53-induced growth suppression, into a p53-deficient mouse prostate cancer cell line using a recombinant adenoviral vector (Ad5CMV-p53 or Ad5CMV-p21). Elevated levels of endogenous mouse p21 mRNA provided evidence for the functional activity of virally transduced p53. Functional activity of viral-transduced p21 was demonstrated through immunoprecipitation of cellular protein extracts, which showed that the viral-transduced p21 associates with cyclin-dependent kinase 2 and was sufficient to down-regulate the activity of the cyclin-dependent kinase by approximately 65%. In vitro growth assays revealed significantly higher growth suppression after Ad5CMV-p21 infection compared to Ad5CMV-p53. In vivo studies in syngeneic male mice with established s.c. prostate tumors demonstrated that the rate of growth and final tumor volume were reduced to a much greater extent in mice that received intratumor injection of Ad5CMV-p21 compared to Ad5CMV-p53. In addition, the survival of host animals bearing tumors that were infected with Ad5CMV-p21, but not Ad5CMV-p53, was significantly extended. These data suggest that Ad5CMV-p21 may be effective as a therapeutic agent for prostate cancer.
Adenoviridae↗
2,5-Hexanedione exposure alters microtubule motor distribution in adult rat testis.
2,5-Hexanedione (2,5-HD) exposure in rats causes a progressive Sertoli cell injury culminating in testicular atrophy. Morphological injury is preceded by alterations in the assembly characteristics of tubulin isolated from exposed rat testes. This is followed by decreased seminiferous tubule fluid (STF) secretion by Sertoli cells and an increase in the number and size of Sertoli cell vacuoles. The possible involvement of microtubules and microtubule motor-dependent transport processes in STF secretion by Sertoli cells prompted us to examine the immunodistribution of the microtubule motors cytoplasmic dynein and kinesin during and after 2,5-HD exposure in rats. Three weeks following the commencement of exposure (1% 2,5-HD in the drinking water), the intensity of apical Sertoli cell cytoplasmic dynein immunofluorescence declined. This staining deficit became statistically significant by 4 weeks of exposure. Accompanying this change, there was progressive disruption of the immunodistribution of cisternal Golgi elements and associated kinesin immunoreactivity. The decrease in apical Sertoli cell cytoplasmic dynein immunofluorescence and disruption of Golgi and kinesin immunoreactivity suggest that 2,5-HD-induced alterations in Sertoli cell-mediated transport and secretory events could involve deficits in microtubule-dependent motor function.
Animals↗
Paediatric pain assessment in intensive care units.
In this exploration of the problem of assessing children' pain in intensive care units (ICUs), literature spanning the last 10 years was reviewed to identify factors that affect pain assessment, such as developmental stage, health professionals' attitudes and myths. Selected pain assessment tools are briefly described and evaluated for use in intensive care with children. Although this review is small, it is clear that despite nurses' recognition of the need for pain assessment in children, and the appearance of many new assessment tools, health professionals may still not be managing paediatric pain effectively. The search also revealed that little appears to have been written about this problem as it occurs in ICUs, and more research is indicated.
Adolescent↗
Stem cell kinetics in rat testis after irreversible injury induced by 2,5-hexanedione.
Stem cells provide a continuous supply of committed progenitor cells for the process of spermatogenesis. In rodents, stem cells have been identified as single, undifferentiated type A spermatogonia. The rate of stem cell division has not been definitively determined because of difficulty in locating stem cells among a normal compliment of germ cells. The testicular toxicant 2,5-hexanedione (2,5-HD) induces irreversible testicular atrophy with only Sertoli cells and spermatogonia remaining after injury. Stem cell kinetics could be assessed in this toxicant model because of the absence of most mature germ cells. It is also not known if 2,5-HD-exposed rats possess an active stem spermatogonia population. Charles River CD rats were exposed to 1% 2,5-HD in drinking water for 5 wk. At 7 or 35 wk following toxicant exposure, rats were exposed to bromodeoxycytidine continuously via Alzet mini-pumps for 1-28 days. Serial cross sections of testis were used to identify single stem spermatogonia and to determine whether the cells were positive or negative for bromodeoxyuridine incorporation. We obtained a continuous labeling index for stem cells from rats 7 and 35 wk after 2,5-HD exposure and found that stem cells had a cell cycle time of approximately 8-14 days at both time points after toxicant exposure. In conclusion, we have developed a method for the assessment of stem cell kinetics and verified the presence of an actively dividing stem cell population in irreversibly injured testes.
Animals↗
Management of gunshot injuries to the penis and anterior urethra.
OBJECTIVE: To verify the appropriate methods of diagnosis and treatment of gunshot injuries to the penis and anterior urethra. DESIGN: Retrospective study. MATERIALS AND METHODS: Fourteen patients presented over 5 years with gunshot wounds to the male genitalia with injuries involving the penis and or the anterior urethra. All patients underwent a full physical examination and retrograde urethrogram to fully stage suspected injuries. RESULTS: Of the nine patients sustaining penile wounds, four were superficial, requiring only debridement, and five involved the corpus cavernosum, necessitating formal repair. Physical findings of an expanding hematoma, a palpable corporeal defect, and excessive bleeding via the wounds were indicative of cavernosal injury and warranted a penile exploration. All patients were potent in follow-up, although two patients with extensive injuries did complain of curvatures. Retrograde urethrograms noted anterior urethral injuries in eight patients, three of whom also had sustained cavernosal injuries. Five were repaired primarily, and three were treated by urinary diversion via a suprapubic tube. Three patients developed urethral strictures: one in the primary repair group and two in the diversion group. CONCLUSIONS: The preferred method of handling low-velocity gunshot wounds to the penis and anterior urethral includes debridement of superficial wounds, repair of cavernosal defects, and primary repair of urethral injuries wherein tissue loss is not extensive to result in high-potency rates and lower rates of urethral stricture disease.
Adolescent↗
Extensive corporeal fibrosis after penile irradiation.
A potent man with early signs and symptoms of Peyronie's disease 3 months in duration received 1,200 rad of external beam radiation to the penis and presented 5 months later with impotence. Physical examination revealed diffusely woody indurated corporeal tissue. Nocturnal penile tumescence testing was abnormal and pharmaco-cavernosometry demonstrated diffuse corporeal veno-occlusive dysfunction. Treatment by penile injections was unsuccessful. During penile prosthesis implantation bilateral rubbery erectile tissue was encountered, requiring extensive bilateral corporotomy and sharp corporeal tissue excision for prosthesis insertion. Histological analysis of excised corporeal tissue demonstrated extensive corporeal fibrosis and arterial vasculopathy. Computer assisted color histomorphometry revealed that the mean percentage of trabecular smooth muscle area to total erectile tissue area was 26.5 +/- 15.8 (normal 40 to 52%). Immunohistochemical staining with desmin confirmed extensive fibrosis. The most likely explanation for severe corporeal fibrosis is penile irradiation. The hypothesized mechanism of radiation associated fibrosis is ionizing injury to the endothelial cells of the lacunar spaces and cavernous/helicine arteries, which induced irreversible corporeal extracellular matrix structural changes. Penile irradiation, like vascular disease and priapism, is a potential cause of diffuse corporeal fibrosis.
Adult↗
Kinematics and myoelectric activity during stair-climbing ergometry.
Stair-climbing ergometry has become a popular mode of aerobic exercise, yet little research on the biomechanics of stair-climbing ergometry has been reported. This study was conducted to evaluate kinematics and myoelectric activity in major agonist muscle groups over 22 minutes of stair-climbing ergometry at 75% of each subject's predicted VO2max. Data were captured over 30-second intervals beginning at 3.5, 9.5, 15.5, and 21.5 minutes of exercise. Multivariate analysis of variance for the kinematic variables revealed a significant (p < 0.05) change in hand placement from a higher to a lower position over time. Multivariate analysis of variance for the electromyographic values revealed a significant (p < 0.05) decrease in activity in the gluteus maximus and vastus lateralis between 3.5 and 9.5 minutes, representing an adjustment to the exercise workload. The normal range of motion and trunk angle values documented should prove helpful to fitness and rehabilitation specialists in prescribing stair-climbing ergometry.
Adult↗
Systemic sclerosis and impotence: a clinicopathological correlation.
A hypothesis of the mechanism of systemic sclerosis associated impotence was developed by making a clinicopathological correlation between the results of preoperative erectile function testing and those of pathological examination of excised erectile tissue in an impotent man with systemic sclerosis. Preoperative examination revealed firm corporeal tissue with diminished penile stretch capability. Pharmacocavernosometry/pharmacocavernosography under conditions consistent with trabecular smooth muscle relaxation revealed severe diffuse corporeal veno-occlusive dysfunction. During penile implantation surgery the compact erectile tissue was unable to be dilated and required sharp corporeal tissue excision under direct vision to achieve cylinder insertion. Histological investigation of the excised corporeal tissue demonstrated severe corporeal fibrosis. Computer assisted color histomorphometry revealed that the mean percentage of trabecular smooth muscle area to total erectile tissue area was 18.2 +/- 13.9% (normal 40 to 52). Immunohistochemical staining with desmin, a protein found in smooth muscle, verified prolific corporeal fibrosis. In situ hybridization of the corporeal tissue demonstrated messenger ribonucleic acid collagen and fibronectin messenger ribonucleic acid expression. Strong hybridization signals were found in mesenchymal cell types, including trabecular smooth muscle cells. In summary, clinicopathological correlation revealed that veno-occlusive dysfunction and loss of penile length were secondary to the excessive accumulation of extracellular matrix, partially due to trabecular smooth muscle cells undergoing synthetic as opposed to contractile phenotypic activity.
Adult↗
Traumatic rupture of a renal pelvis obstructed at the ureteropelvic junction: case report.
Blunt abdominal trauma is a rare cause of injury to the upper ureter and renal pelvis. However, a pre-existing renal abnormality predisposes the kidney sustaining even minor trauma to serious injury. A case of a ruptured renal pelvis congenitally obstructed at the ureteropelvic junction following relatively minor trauma is presented, the literature reviewed, and susceptibility factors for traumatically induced hydronephrotic rupture discussed.
Abdominal Injuries↗
Unsuspected malignant pheochromocytoma: appearance on thallium and gallium scans.
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Adrenal Gland Neoplasms↗
A tumorigenic murine Sertoli cell line that is temperature-sensitive for differentiation.
The Sertoli cell is the epithelial cell within the seminiferous tubule responsible for supporting germ cells. Most current in vitro studies of Sertoli cell function use primary cultures because of the limited number of available Sertoli cell lines. In addition, few in vivo models of Sertoli cell malignancy have been described. In this study, a tumorigenic Sertoli cell line was developed by infection of isolated murine Sertoli cells by simian virus 40 tsA255; the ts mutation causes the inactivation of the large T antigen at elevated temperatures. A cloned Sertoli cell line, called S14-1, demonstrated temperature-dependent growth in soft agar and formed tumors in nude mice. Electron microscopy of the S14-1-derived tumor revealed extensive basal intercellular junctions and tubulobulbarlike processes supporting its Sertoli cell origin. Cytogenetic analysis showed that S14-1 cells were aneuploid with an average of 70 chromosomes per cell. At the nonpermissive (40 C) temperature, S14-1 cells in vitro demonstrated a reduced growth rate, enhanced secretion of transferrin, and increased expression of sulfated glycoprotein-2 messenger RNA, indicating the cells manifested increased differentiation following large T antigen inactivation. The murine S14-1 Sertoli cell line should be useful for both in vitro studies of Sertoli cell function and in vivo studies of Sertoli cell malignancy.
Animals↗
Comments on cosmetic surgery.
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Animal Welfare↗
The effect of short-term fasting and a single meal on protein synthesis and oxygen consumption in cod, Gadus morhua.
Rates of protein synthesis and oxygen consumption (MO2) in cod were compared in both fasted and refed animals. During a 14-day fast both protein synthesis and respiration rates fell to stable values after 6 days. When a meal of whole sandeel at 6% body weight was fed to fish fasted for 6 days, protein synthesis and MO2 increased to a maximum at between 12 and 18 h after feeding. Peak MO2 was about twice the pre-feeding values, while whole animal protein synthesis increased four-fold. There were differences between tissues in the timing of maximum protein synthesis; the liver and stomach responded faster than the remainder of the body. Maximum protein synthesis rates in the liver and stomach occurred at 6 h after feeding, at which time their calculated contribution to total MO2 was 11%. Similar calculations suggested that the integrated increment in whole animal protein synthesis contributed between 23% and 44% of the post-prandial increase in MO2. It was concluded that protein synthesis is an important contributor to increased MO2 after feeding in cod.
Animals↗
Sertoli cells isolated from adult 2,5-hexanedione-exposed rats exhibit atypical morphology and actin distribution.
Sertoli cells were isolated from 2,5-hexanedione (2,5-HD)-exposed, cryptorchid and 21-day-old rats in order to examine alterations in in vitro Sertoli cell transferrin secretion, germ cell adhesion, in vitro morphology, and cytoskeletal organization which might be involved in the irreversibility of 2,5-HD-induced testicular injury. Sertoli cells isolated from 21-day-old, cryptorchid and 2,5-HD-exposed rats exhibited similar transferrin secretion as measured using an enzyme-linked immunosorbent assay. Germ-cell adhesion was measured using [3H]leucine-labeled immature rat germ cells and revealed similar levels of germ-cell binding in Sertoli cell cultures isolated from the three groups of rats. Differential interference contrast microscopy demonstrated that Sertoli cells isolated from 2,5-HD-exposed rats possessed an atypical spindle shape and long cytoplasmic processes. The immunofluorescent distribution of tubulin and vimentin corresponded with the morphological appearance of the cells with well-defined microtubule and intermediate filament networks which, in the cells isolated from 2,5-HD-exposed rats, extended into the cytoplasmic processes. Rhodamine-conjugated phalloidin-labeled actin stress fibers were decreased in density within the 2,5-HD-exposed rat Sertoli cells. The altered morphology and distribution of actin filaments within Sertoli cells isolated from adult 2,5-HD-exposed rats may reflect an underlying insult which is involved in the irreversible nature of 2,5-HD intoxication.
Actins↗
Functional expression of the dihydrofolate reductase and thymidylate synthetase activities of the human malaria parasite Plasmodium falciparum in Escherichia coli.
We have developed a recombinant system that directs the functional expression from Escherichia coli of both dihydrofolate reductase-thymidylate synthetase (DHFR-TS) and the isolated DHFR domain from Plasmodium falciparum. Both products are inhibitory to a number of E. coli cell lines to the extent that cell growth ceases immediately upon induction. This dramatic inhibition is not seen in strain AB1899, in which amounts of plasmodial protein of up to 100 times the basal E. coli TS level can be accumulated. However, as well as the full-length DHFR-TS molecule, smaller proteins carrying an intact TS substrate-binding site are produced. These represent ca. 60-75% of the total plasmodial protein expressed and are observed in every E. coli strain examined. We show that they are not derived by degradation of the parent DHFR-TS molecule, but can be correlated with the sizes of proteins expected to be produced if erroneous initiation of translation were occurring at 3 internal methionine residues.
Animals↗