Internet biomolecular resources.
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Publications and source records attributed to J L Cook.
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Expression of 18 genes was examined at 8 different time points between 1 h and 28 days following cryogenic rat brain injury. The genes include thymidine kinase (TK), p53 tumor suppressor, c-fos, renin, myelin basic protein (MBP), proteolipid protein (PLP), transferrin, transferrin receptor, platelet-derived growth factor A (PDGF A), platelet-derived growth factor B (PDGF B), platelet-derived growth factor receptor alpha (PDGF alpha receptor), platelet-derived growth factor receptor beta (PDGF beta receptor), glial fibrillary acidic protein (GFAP), transforming growth factor-beta 1 (TGF-beta 1), basic fibroblast growth factor (bFGF), fibroblast growth factor receptor-1 (FGF-R1), insulin-like growth factor-1 (IGF-1), and somatostatin. Time courses of gene expression were determined for RNAs derived from hippocampus and cortex. Genes were divided into categories based upon those in which statistically significant changes in expression were first observed at or before 24 h (early genes) and those in which changes were first observed at or after 72 h (late genes). In the present model, many genes demonstrate elevated RNA levels in the cortex prior to hippocampus, following injury. RNAs transcribed from late genes tend to be elevated concurrently in cortex and hippocampus.
A common pattern of birth defects was reported in children born to alcoholic women over 20 years ago. Shortly thereafter the constellation of defects became known as the Fetal Alcohol Syndrome, and reports from around the world served to acknowledge the pervasiveness of the disorder. Simultaneously with the clinical reports, animal models were developed to characterize the full spectrum of the teratogenic effects of ethanol. Not only did these animal models serve to define the actions of ethanol on fetal growth and development at the molecular pharmacological, neuroanatomical, and behavioral level, but unintentionally, they have resulted in renewed scientific interest in the effects of ethanol on pregnancy and parturition itself. The purpose of this review is twofold. First we will consolidate and summarize data from both clinical and basic research that pertains to ethanol and parturition. These data will demonstrate that ethanol consumption during pregnancy results in both delayed as well as premature delivery depending upon the pattern of consumption and timing of exposure. With these data as a background, the second objective will be to present a theoretical case for prostaglandins as possible mediators of ethanol-induced effects on the onset of parturition.
Concurrent changes in expression of eight genes were examined following cryogenic rat brain injury. Cortical RNA levels were catalogued at time 0, and at 1 h and 1 week following injury. The genes include thymidine kinase (TK), c-fos, renin, myelin basic protein (MBP), proteolipid protein (PLP), glial fibrillary acidic protein (GFAP), insulin-like growth factor-1 (IGF-1), and somatostatin. All demonstrate increased expression following injury. Renin and c-fos exhibit detectable changes as early as 1 h post-injury.
Symptoms of jumper's knee (patellar tendinosis) are not easily quantified and this may explain why there are no evidence-based guidelines for managing the condition. A simple, practical questionnaire-based index of severity would facilitate jumper's knee research and subsequently, clinical management. Thus we devised and tested the Victorian Institute of Sport Assessment (VISA) questionnaire. The brief questionnaire assesses (i) symptoms, (ii) simple tests of function and (iii) ability to play sport. Six of the eight questions are scored on a visual analogue scale from 0-10 with 10 representing optimal health. The maximal VISA score for an asymptomatic, fully performing individual is 100 points and the theoretical minimum is 0 points. We found the VISA scale to have excellent short-term test-retest, and inter-tester reliability (both, r>0.95) as well as good short-term (one week) stability (r=0.87). Mean (SD) of the VISA scores ranged from 95 (8) points in asymptomatic control subjects to 55 (12) points in patients who presented to a sports medicine clinic with jumper's knee and 22 (17) points in patients before surgery for chronic jumper's knee. Six- and twelve-months after surgery VISA scores returned to 49 (15) and 75 (17) points respectively, mirroring clinical recovery. We conclude that the VISA score is a reliable index of the severity of jumper's knee that has potential to aid clinicians and researchers.
OBJECTIVE: To compare patellar tendon sonographic findings in active, currently asymptomatic, elite athletes with those in nonathletic controls. DESIGN: Cross-sectional cohort study with convenience control sample. SETTING: The Victorian Institute of Sport Tendon Study Group, an institutional elite athlete study group in Australia. PATIENTS AND PARTICIPANTS: Two hundred elite male and female athletes from the sports of basketball, cricket, netball, and Australian rules football. Forty athletes who had current symptoms of jumper's knee were excluded from analysis, leaving 320 subject tendons in athletes who were currently asymptomatic. Twenty-seven nonathletic individuals served as controls. MAIN OUTCOME MEASURE: Sonographic patellar tendon appearance. We measured the dimensions of subject tendons and noted the presence or absence of hypoechoic regions and tendon calcification. Dimensions of hypoechoic regions were measured, and approximate cross-sectional areas were calculated. Chi-squared analysis was used to test the prevalence of hypoechoic regions in subjects and controls and men and women. RESULTS: In currently asymptomatic subjects, hypoechoic regions were more prevalent in athlete tendons (22%) than in controls (4%), in male subject tendons (30%) than in female subjects (14%), and in basketball players (32%) than in other athletes (9%) (all p < 0.01). Bilateral tendon abnormalities were equally prevalent in men and women but more prevalent in basketball players (15%) than in other athletes (3%) (p < 0.05). Sonographic hypoechoic regions were present in 35 of 250 (14%) patellar tendons in athletes who had never had anterior knee pain. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas were present in asymptomatic patellar tendons of a proportion of elite athletes but rarely present in controls. This has implications for clinicians managing athletes with anterior knee pain.
The patellar tendon donor site of 20 patients who underwent anterior cruciate ligament (ACL) reconstruction using the patellar tendon tissue as autograft was examined with high resolution 7.5 MHz ultrasound. The patients were randomly divided into four groups and studied at 3, 6, 9 or 12 months postoperatively. The size of the postoperative tendon defect was measured just distal to the lower pole of the patella. The size of the tendon defect diminished progressively from a mean of 109 mm2 at 3 months to a mean of 23 mm2 at 12 months. Increasing echogenicity was first noticed 12 months after tendon repair. Seven patients developed clinical features postoperatively of jumper's knee (patellar tendinosis). There were no ultrasound signs that differentiated these patients from asymptomatic patients. It is concluded that ultrasound provides objective evidence of patellar tendon healing after ACL reconstruction: the surgical defect diminished in size and became echogenic after a period of 12 months.
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Although SV40 transforms cells from many species, transformed cells from species other than the Syrian hamster are rarely tumorigenic in immunocompetent animals. However, secondary manipulations of SV40-transformed cells can result in increased tumorigenicity. Some early observations on tumour induction by SV40 and transformed cells will be followed by a selected review of evidence suggesting that tumorigenicity of SV40-transformed cells involves serial mutations. An SV40-transformed rat cell model will be described to illustrate the changes in tumorigenic phenotype that can occur during tumour progression. This information will be used to propose that SV40 immortalization of cells (other than hamster cells) is only the first in a series of steps in the pathway toward tumorigenicity and that a complete understanding of the oncogenicity of SV40 will require definition of the secondary genetic events which complement SV40 immortalization to create the fully tumorigenic phenotype.
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Multidrug-resistant tuberculosis (MDRTB) has emerged as a challenging clinical problem in both HIV-infected and -uninfected individuals. In this study, immune responses from HIV-negative patients with MDRTB were compared with those of healthy purified protein derivative (PPD)-positive and PPD-negative individuals. These responses were characterized by measuring the proliferation and cytokine production from PBMCs stimulated in vitro with Mycobacterium tuberculosis, PPD, or mitogens. MDRTB patients with CD4 counts >500/microl stimulated in vitro with M. tuberculosis had similar immune responses (proliferation, IFN-gamma, and IL-2 production) as the PPD-positive and -negative controls. By contrast, MDRTB patients with CD4 counts <500/microl had markedly deficient immune responses to similar stimuli. In these patients, IFN-gamma production could be restored by adding IL-12 to the in vitro cultures. IL-12 also caused a striking increase in the amount of IFN-gamma produced from PBMCs of both PPD-positive and -negative controls. The role of endogenous IL-12 production was also studied. Addition of anti-IL-12 to cultures resulted in a two- to eightfold decrease in IFN-gamma production in response to PHA stimulation. Inhibition of IFN-gamma was also observed when cells were stimulated by M. tuberculosis and PPD. Using Staphylococcus aureus Cowan strain as a mitogenic stimulus, IL-12 p70 was produced in similar amounts in all groups tested. TNF-alpha production was also assessed from cells stimulated by M. tuberculosis. Addition of IL-12 to the cultures did not cause a significant enhancement of TNF-alpha production. Last, production of IL-10 and IL-4 in response to M. tuberculosis and PHA, respectively, was not significantly different among all groups tested. These results suggest that patients with MDRTB tuberculosis with CD4 T cell counts <500/microl have impaired IFN-gamma and IL-2 responses and might benefit by adjunctive IL-12 therapy.
Surgical treatment of OA is appropriate when conservative therapy fails or is inadequate. The veterinary orthopedist's goals in treatment should be to alleviate pain, maintain function, and prevent or remove the potential for further degeneration of the joint. Currently, in veterinary surgery, THR and femoral head and neck excision are the primary treatments for OA of the coxofemoral joint. Other joints are treated primarily by arthrodesis or excision arthroplasty. Arthroscopy is proving to be a valuable tool in the diagnosis and treatment of OA, and total stifle and elbow replacement and cartilage resurfacing through chondrocyte grafting are on the horizon as potential treatment options.
These studies were designed to determine the effect of acute alcohol treatment on gestational length and to probe for a mechanism underlying alcohol-induced early onset of parturition (EOP) in mice. Experiment 1: alcohol increases the incidence of EOP. Pregnant C57BL/6J mice were given alcohol (0, 4, 5 or 6 g kg(-1), i.g.) on Gestational Day (GD) 10, 15, 16, 17 or 18. Deliveries were monitored every 6 h from GD 18. Results indicated that 6 g kg(-1) alcohol treatment on GD 17 or 18 increased the incidence of EOP. Experiment 2: prostaglandins (PGs) play roles in parturition. The purpose of Experiment 2 was to determine whether PGs mediate alcohol-induced EOP in mice. The results indicated that pretreatment on GD 17 with aspirin, a prostaglandin synthesis inhibitor, prevented alcohol-induced EOP. These data suggest that alcohol-induced EOP in mice may be mediated by PGs. Experiment 3: PGs are influenced by alcohol and are triggers of labour. Experiment 3 measured uterine PGs associated with the onset of alcohol-induced EOP in mice. Alcohol increased uterine PGE and PGF2alpha, with PGE levels higher than control before labour, and elevated PGF2alpha levels correlating with labour. Changes in gestational length have important implications for pregnancy outcome, as well as for normal fetal growth and development.
OBJECTIVE: To compare patellar tendon sonographic findings at baseline and at follow-up in active female basketball players with and without symptoms of jumper's knee. We hypothesized that baseline sonographic morphology would not reliably predict prognosis and, in particular, that it would not predict the need for surgery. DESIGN: Prospective longitudinal study with 12-month minimum follow-up. SETTING: Institutional elite athlete study group in Australia (Victorian Institute of Sport Tendon Study Group). PATIENTS AND PARTICIPANTS: A total of 15 female elite basketball players with 23 sonographically abnormal tendons and 15 matched control basketball players with 23 sonographically normal tendons. MAIN OUTCOME MEASURES: Sonographic patellar tendon appearance and clinical assessment of symptoms of jumper's knee at baseline and follow-up. Dimensions of abnormal regions were measured. RESULTS: At baseline, the 23 subject tendons contained sonographic hypoechoic regions (six currently symptomatic, eight previously symptomatic only, and nine never symptomatic). At follow-up, the hypoechoic areas in seven tendons had resolved (and caused no symptoms), the hypoechoic areas in 11 tendons had remained essentially the same size (five were symptomatic), and the hypoechoic areas in five tendons had expanded (three symptomatic). At baseline, there were no differences between the mean +/- SD cross-sectional areas of the abnormalities in the tendons that subsequently resolved (15.9 +/- 10.1 mm2) and those that remained unchanged (39.3 +/- 25.8) or expanded (25.3 +/- 12.5). The presence of a baseline sonographic abnormality predicted symptoms of jumper's knee at follow-up (p < 0.05), but the presence of symptoms of jumper's knee at baseline also predicted symptoms at follow-up (p < 0.05). No subject or control missed any games or underwent surgical treatment. CONCLUSIONS: Patellar tendon sonographic hypoechoic areas can resolve, remain unchanged, or expand in active sports-women without predicting symptoms of jumper's knee. Thus, symptoms were not directly related to sonographic tendon morphology. Sonographic hypoechoic regions ought not to constitute per se an indication for surgery.
OBJECTIVES: Jumper's knee causes significant morbidity in athletes of all standards. However, there are few reference data on the clinical course of this condition in a large number of patients, and the aim of this study was to rectify this. METHODS: A retrospective study of the course of jumper's knee in 100 athletes who presented to a sports medicine clinic over a nine year period was carried out. Subjects completed a questionnaire designed to collect details of sport participation, symptoms, and time out of sport. Ultrasonographic results were recorded from the radiologists' reports. Histopathological results were obtained for patients who had surgery. RESULTS: Forty eight subjects recalled that symptoms of jumper's knee began before the age of 20 years. Symptoms prevented 33 from participating in sport for more than six months, and 18 of these were sidelined for more than 12 months. Forty nine of the subjects had two or more separate episodes of symptoms. Ultrasonography showed a characteristics hypoechoic region at the junction of the inferior pole of the patella and the deep surface of the patellar tendon. Histopathological examination showed separation and disruption of collagen fibres on polarisation light microscopy and an increase in mucoid ground substance consistent with damage of tendon collagen without inflammation. CONCLUSIONS: Jumper's knee has the potential to be a debilitating condition for a sports person. About 33% of athletes presenting to a sports medicine clinic with jumper's knee were unable to return to sport for more than six months.
Heme oxygenase (HO)-mediated heme degradation is the primary mechanism for production of cellular carbon monoxide (CO). Analogous to nitric oxide (NO), CO mediates physiological and cellular functions such as vasodilation, stimulation of guanylate cyclase, and neuronal transmission. In view of accumulating data demonstrating a correlation between the activity of these two gaseous molecules and that the predominant source of CO is via HO catalysis, we hypothesized that NO regulates HO expression. We demonstrate that the NO donor spermine NONOate (SNN) increases steady-state levels of HO-1 mRNA in aortic vascular smooth muscle cells (aSMC) in both a time- and dose-dependent manner. The accumulation of HO-1 mRNA that correlated with increased HO-1 protein synthesis resulted from both an increased rate of gene transcription and a decreased rate of mRNA turnover. Inhibition of the NO-induced HO-1 mRNA expression by cycloheximide suggests that new protein synthesis is required for increased HO-1 gene expression. Induction of HO-1 expression by SNN occurs in a guanosine 3',5'-cyclic monophosphate (cGMP)-independent manner because exposure of cells to 8-bromoguanosine 3',5'-cyclic monophosphate, a cGMP analog, did not increase HO-1 mRNA levels, and pretreatment of cells with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a selective guanylate cyclase inhibitor, did not prevent SNN-induced HO-1 mRNA accumulation. The antioxidant N-acetyl-L-cysteine markedly inhibited SNN-induced HO-1 mRNA expression, whereas peroxynitrite did not induce HO-1 expression in aSMC. Interestingly, CO did not attenuate NO-induced HO-1 expression through an autocrine negative feedback mechanism as had been observed for hypoxia-induced HO-1 expression. These data provide evidence for an important regulatory network between NO and CO via HO-1.
OBJECTIVE: To determine the effects of transplantable substrates on canine chondrocytes grown in three-dimensional culture. ANIMALS: 3 canine cadavers. PROCEDURE: Articular cartilage harvested from canine cadavers was used to obtain chondrocytes for primary culture. Subcultured chondrocytes were grown in agarose alone (AG), or in agarose on canine cancellous bone (CB), polypropylene mesh, or oxidized regenerated cellulose substrate. Cell proliferation, proteoglycan and glycosaminoglycan (GAG) production, and collagen production were assessed on days 3, 6, 10, 15 and 20. RESULTS: Chondrocytes from groups AG and CB proliferated and produced matrix over the entire 20-day study period. Group-CB chondrocytes had significantly more GAG than did chondrocytes of all other groups on days 6 (P = 0.0297) and 15 (P = 0.00272). Those of groups AG and CB contained significantly (P = 0.0235) more GAG on day 20. Chondrocytes of the polypropylene mesh group proliferated and produced matrix through day 10 in culture, but were no longer viable and had no matrix production on days 15 and 20. Regenerated cellulose appeared to be toxic to canine chondrocytes during all stages of in vitro three-dimensional culture. CONCLUSIONS: Three-dimensional culture of canine chondrocytes in agarose appears to produce favorable results with respect to chondrocyte proliferation and matrix production. Canine CB appears to have beneficial effects with regard to early GAG synthesis. Polypropylene mesh and oxidized regenerated cellulose had detrimental effects on cellular proliferation and matrix production.