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Biomedical subjects

J L Cook

Publications and source records attributed to J L Cook.

At least 73 records · Page 4Linked to original sources
PubMed1997

Early onset of parturition induced by acute alcohol exposure in C57BL/6J mice: role of uterine PGE and PGF2alpha.

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.

Animals↗
PubMed1997

Patellar tendon ultrasonography and jumper's knee in female basketball players: a longitudinal study.

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.

Analysis of Variance↗
PubMed1997

A cross sectional study of 100 athletes with jumper's knee managed conservatively and surgically. The Victorian Institute of Sport Tendon Study Group.

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.

Adolescent↗
PubMed1997

Regulation of heme oxygenase-1 gene expression in vascular smooth muscle cells by nitric oxide.

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.

Animals↗
PubMed1997

Three-dimensional culture of canine articular chondrocytes on multiple transplantable substrates.

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.

Analysis of Variance↗
PubMed1997

The importance of Java and CORBA in medicine.

One of the most powerful tools available for telemedicine is a multimedia medical record accessible over a wide area and simultaneously editable by multiple physicians. The ability to do this through an intuitive interface linking multiple distributed data repositories while maintaining full data integrity is a fundamental enabling technology in healthcare. We discuss the role of distributed object technology using Java and CORBA in providing this capability including an example of such a system (TeleMed) which can be accessed through the World Wide Web. Issues of security, scalability, data integrity, and usability are emphasized.

Computer Communication Networks↗
PubMed1997

Aging of the skin: implications for cutaneous surgery.

There are precious few benefits, save perhaps experience and wisdom, that those of advanced age may claim over those who continue to dwell in their youth. One somewhat paradoxical advantage, however, is the ability of older patients to apparently heal better than younger patients after cutaneous surgery. In older patients, the incision lines are less red, the scarring is less hypertrophic, and "normalization" of appearance occurs more rapidly. And yet, the "wrapping" does not necessarily reflect the contents of the "box." Unfavorable age-dependent alterations in the physical properties of the skin and the wound-healing cascade may affect the viability and structural integrity of the postoperative result. Surgery on the aged population must therefore couple the optimism for a pleasing aesthetic result with the caution reflecting a cutaneous substrate altered by the perturbations of time. This somewhat shaky balance, although not altogether understood, is worthy of study by the physician approaching the patient of advanced age.

Aged↗
PubMed1996

Role of p300-family proteins in E1A oncogene induction of cytolytic susceptibility and tumor cell rejection.

The mechanism by which the adenoviral (Ad) E1A oncogene induces cellular susceptibility to lysis by killer lymphocytes involves interactions between its first exon and different second-exon accessory regions. Mutational analysis showed that two first-exon regions--one in the N terminus and one in the conserved region 1 (CR1) domain--are necessary for this activity. E1A complex formation with cellular p300 protein through these first-exon-encoded regions correlated with induction of the cytolytic susceptible phenotype but was only effective in the context of E1A second-exon expression. An E1A first-exon deletion that prevented p300 binding eliminated both oncoprotein-induced cytolytic susceptibility and rejection of transfected sarcoma cells by immunocompetent animals. These results suggest that the E1A oncogene induces cytolytic susceptibility and tumor rejection by interactions with cellular proteins of the p300 family that affect transcription of genes involved in the cellular response to injury inflicted by host killer cells.

Adenoviridae↗
PubMed1996

E1A oncogene expression in target cells induces cytolytic susceptibility at a post-recognition stage in the interaction with killer lymphocytes.

E1A oncogene expression increases the susceptibility of cells from several species to lysis by natural killer lymphocytes (NK cells). We asked whether this E1A-induced cellular phenotypic conversion is specific for NK cell recognition interactions with target cells or whether it results from an E1A effect that is mediated independently of recognition. E1A-positive and E1A-negative cell pairs were compared for cytolytic susceptibility to other types of killer cells that use recognition mechanisms different from those of NK cells. E1A-positive, NK-susceptible target cells were also preferentially lysed by cytotoxic T lymphocytes (CTL) that recognize only foreign MHC molecules, lymphokine-activated T cells that lack recognition specificity, and CTL whose conventional recognition mechanisms were bypassed by lectin treatment of target cells. E1A expression increased cellular susceptibility to both major mechanisms of killer cell lysis-perforin/granzyme lysis and Fas-dependent lysis. Furthermore, anti-Fas antibody lysed E1A-positive, but not E1A-negative, cells expressing comparable levels of cell surface Fas antigen. These results indicate that a major mechanism by which E1A induces cellular susceptibility to lysis involves a stage in the interaction of killer cells with their targets that follows and is independent of cell surface recognition.

Adenovirus E1A Proteins↗
PubMed1996

E1A second exon requirements for induction of target cell susceptibility to lysis by natural killer cells: implications for the mechanism of action.

The E1A oncogene of adenovirus type 5 induces susceptibility of mammalian cells to lysis by natural killer lymphocytes (NK cells). It is unknown whether sensitization to NK killing is mediated directly by targeting effects of interactions between E1A peptides and cell surface MHC molecules or indirectly by an E1A activity that requires structural integrity of the oncoprotein. To discriminate between these hypotheses, rat and hamster cells expressing wild type E1A were contrasted with those expressing truncated products resulting from E1A termination or deletion mutations. Transfected rat cells, expressing truncated proteins from the E1A first exon that encodes MHC-binding peptides, remained resistant to lysis by NK cells, whereas cells expressing full-length E1A protein were highly susceptible to lysis. Studies of infected hamster cells showed that addition of either of two, nonoverlapping, second exon regions reconstituted cytolytic susceptibility induction by E1A. The results do not support the E1A-peptide-MHC hypothesis, since no single E1A peptide coding region was sufficient to convey cytolytic susceptibility to expresser cells. The data indicate that coordinate functions of the E1A first exon and redundant accessory regions in the second exon are required for E1A-induced susceptibility to NK killing.

Adenovirus E1A Proteins↗
PubMed1996

Cocaine does not affect prostacyclin, thromboxane or prostaglandin E production in human umbilical veins.

Vasoactive prostaglandins have been reported to mediate umbilical/placental blood flow in humans. Since it has been suggested that cocaine exerts its teratogenic action via vasoconstriction and a corresponding reduction in blood flow, it is reasonable to hypothesize that cocaine influences the vasoactive prostaglandins such that blood flow would be affected. The purpose of this study, therefore, was to determine the effects of cocaine on the vasoactive prostaglandins prostacyclin, thromboxane, and prostaglandin E, using human umbilical veins. Prostacyclin (PGI2), thromboxane (TXA2), and prostaglandin E (PGE) levels were measured from human umbilical veins collected at term. The veins were perfused in a closed system with either a 50 micrograms/ml, a 100 micrograms/ml, a 200 micrograms/ml, or a 400 micrograms/ml cocaine solution for 60 min, and the prostaglandins were measured by radioimmunoassay of their stable metabolites. Data were analyzed by ANOVA, and post-hoc analyses were performed by Fisher's Protected Least Significant Difference Test. Cocaine did not influence PGI2, TXA2, or PGE production (Ps > 0.05) in this series of studies. Thus, contraction of human umbilical vessels and decreased blood flow in human umbilical vessels does not appear to be mediated by changes in the vasoactive prostaglandins.

Cocaine↗
PubMed1996

Suppression of cellular proliferation using p53 DNA recognition site-related oligonucleotides.

A number of oligonucleotides were designed to bind through Hoogsteen triple helix or Watson-Crick hydrogen bonds to the p53 consensus sequence homology localized within the human nontranscribed rRNA spacer region. The oligomers, which bind in vitro to the consensus sequence homology, function as p53 analogues in cells deficient in wild-type p53 protein. Oligomers suppress proliferation of human colon cancer cells by three to eightfold, but only suppress proliferation of normal human mesangial cells or lung fibroblasts by less than 50%. On the basis of these studies, p53 analogues may be used therapeutically to selectively modify proliferation of transformed cells.

Amino Acid Sequence↗
PubMed1996

Increase in vasoactive prostaglandin E production after perfusion in human placental cotyledons.

Studies from our laboratory indicate that prostaglandins may be mediators of at least some of the teratogenic actions of ethanol in both mouse and human tissue model systems. The present studies were designed to evaluate the relationship between ethanol and prostaglandin E (PGE) production in isolated human placental cotyledons. Placentas were obtained immediately after cesarean section delivery. A fetal artery supplying a single cotyledon was identified and cannulated, and the isolated cotyledon was placed in a perfusion chamber where maternal circulation was established and dual circulation continued throughout the perfusion procedure. Antipyrine clearance, oxygen consumption, and placental production of human chorionic gonadotropin were measured to verify tissue viability. PGE levels of the perfusate were measured by radioimmunoassay. Study 1 evaluates the effect of perfusion with 25 and 100 mM ethanol on placental PGE production. It was found that PGE production increased after perfusion with 25 mM ethanol, but not during the perfusion period per se. The paradigm for study 2 was identical to that of study 1, with the addition of a buffer washout period after 100-mM ethanol perfusion. Again, results indicate that perfusate PGE levels were increased in the buffer washout periods after the 25-mM and the 100-mM ethanol perfusions. The effect was not concentration dependent. An increase in circulating PGE associated with ethanol administration may be teratogenic actions and represent a potential mechanism underlying at least some aspects of fetal alcohol syndrome.

Adult↗
PubMed1996

Patellar tendinosis (jumper's knee): findings at histopathologic examination, US, and MR imaging. Victorian Institute of Sport Tendon Study Group.

PURPOSE: To determine the histopathologic findings of patellar tendinosis ("jumper's knee") demonstrated with ultrasonography (US) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-four athletes (28 knees) with jumper's knee (23 men, one women; mean age, 30.9 years) scheduled to undergo open tenotomy underwent US patellar tendon examination. Seventeen patients (19 knees) also underwent MR imaging. Tissue was obtained for histopathologic examination in all 28 cases. Eleven age-, height-, and weight-matched athletes (22 knees) without previous knee symptoms served as control subjects for the US examination. Control material for histopathologic examination was obtained in 20 cadavers (39 knees). Data were analyzed with standard statistical methods. RESULTS: MR imaging and US both revealed an abnormal zone at the proximal patellar tendon attachment. Histopathologic examination revealed mucoid degeneration in all tendons in patients and in 8% (three of 39) of tendons in cadavers (P < .01). CONCLUSION: Jumper's knee is characterized by consistent changes at MR imaging, US, and histopathologic examination and is appropriately described as patellar tendinosis.

Adult↗
PubMed1996

Adenovirus-mediated in vivo gene transfer in a rabbit model of allograft vasculopathy.

BACKGROUND: The long-term success of heart transplantation continues to be in jeopardy because of the development of accelerated vascular myointimal proliferation. Transfer of genes encoding products that can modulate the adverse consequences of phenomena that cause myointimal proliferation, into the allograft vessel wall, may modify these pathologic processes. The purpose of this study was to assess the feasibility of gene transfer and to evaluate the duration of gene expression in a rabbit heterotopic aortic transplant model of allograft vasculopathy. METHODS: The abdominal aortas of 32 outbred New Zealand rabbits were harvested and cross-sectionally bisected (n = 64). Six donor and recipient animals were used in a preliminary study to examine neointimal proliferation without accompanying gene transfer. Of the remaining 26 rabbits (52 allografts), one half of each allograft aorta was administered a control solution, while the other half was incubated with a replication-defective, recombinant, adenoviral vector-encoding, cytomegalovirus promoter-regulated beta-galactosidase. After a 20-minute incubation period, bilateral aorto-carotid transplantations were performed in 26 recipient rabbits. All animals received cyclosporine immunosuppression (10 mg/kg/day subcutaneously). The allografts were harvested at 3, 7, 10, 21, and 28 days after transplantation and assayed for beta-galactosidase activity. RESULTS: Neointimal areas showed an initially slow increase for the first 10 days, followed by a rapid increase up to 21 days, and tended to plateau thereafter. Significant beta-galactosidase was apparent in aortic sections dissected from host rabbits for all time points, except at 28 days. At the 21-day time point, the aortic section from one rabbit was positive, whereas the other two remained negative. However, the one positive section showed intense beta-galactosidase activity, suggesting variability in the experimental model. At 28 days, all aortic sections were negative. CONCLUSIONS: Our findings confirm that genes delivered by this method are expressed for the duration of early rapid intimal proliferation in this heterotopic rabbit model of aortic allograft vasculopathy. These findings suggest that this animal model can be used to assess the therapeutic potential of gene transfer at the time of vascular transplantation and may provide a novel therapeutic approach to prevent or ameliorate the genesis of allograft vasculopathy.

Adenoviruses, Human↗
PubMed1996

Experiences with a distributed virtual patient record system.

TeleMed is a distributed diagnosis and analysis system, which permits physicians who are not collocated to consult on the status of a patient. The patient's record is dynamically constructed from data that may reside at several sites but which can be quickly assembled for viewing by pointing to the patient's name. Then, a graphical patient record appears, through which consulting physicians can retrieve textual and radiographic data with a single mouse click. TeleMed uses modern distributed object technology and emerging telecollaboration tools.

Computer Communication Networks↗