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Biomedical subjects

J L Cook

Publications and source records attributed to J L Cook.

At least 19 recordsLinked to original sources
PubMed2001

In vitro evidence for an intracellular site of angiotensin action.

To differentiate the relative effects of nuclear and cell surface angiotensin II (Ang II) receptors, we mutated the angiotensinogen cDNA by removing the signal sequence-encoding region to produce a nonsecreted form of angiotensinogen [Ang(-S)Exp]. Rat hepatoma cells (which produce renin and angiotensin-converting enzyme mRNAs) were stably transfected with Ang(-S)Exp/pSVL (or a corresponding control) expression plasmid, and mitotic indices were measured for stably transfected cell lines. Experimental clonal cell lines demonstrate an average of 33+/-4.4% (P<0.001) increase in percentage-labeled nuclei compared with control cell lines. The mitogenic effect is blocked by 10(-6) mol/L losartan and by 1 micromol/L renin antisense phosphorothioate oligomers but not by 10(-6) mol/L candesartan. In addition, phenylarsine oxide, which blocks angiotensin receptor internalization, abolishes the losartan inhibitory effect, suggesting that after cell-surface receptor-mediated endocytosis, losartan blocks Ang II nuclear receptors. PDGF mRNA levels are elevated 2.2-fold in Ang(-S)Exp transfected cell lines; addition of anti-PDGF antibodies to the culture medium partially blocks the mitogenic effect of Ang(-S)Exp, while anti-Ang II antibodies have no effect. These results suggest that the Ang(-S)Exp growth effect is due, in part, to autocrine/paracrine stimulation by secreted PDGF after Ang II/Ang II receptor intracellular interactions. We further demonstrate that these cells produce the alternative renin transcript, renin 1A, which apparently lacks a signal sequence and is maintained intracellularly. Collectively, these studies of cultured cells suggest that some cell types may possess components of the renin-angiotensin system that permit intracellular processing of angiotensinogen to Ang II and that Ang II generated intracellularly may be mitogenic.

Alternative Splicing↗
PubMed2001

Synovial fluid markers of osteoarthritis in dogs.

Although none of these markers currently have any clinical applications, researchers have made strong advances in understanding molecular markers of OA and remain optimistic that the goal of identifying clinically useful markers of OA is attainable.(3-6,8,9) Much of this positive sentiment arises from the large array of molecules that have been identified.(8) Molecular markers of the greatest potential clinical use will be those that allow early detection of OA, permit disease progression to be monitored, or allow efficacy of various treatment regimens to be assessed. Earlier and more sensitive detection of OA changes may increase effective opportunities for treatment intervention during reversible phases of the OA disease process and allow more objective assessment of treatment efficacy and prognosis.(6)

Animals↗
PubMed2001

Predictable tissue shrinkage during frozen section histopathologic processing for Mohs micrographic surgery.

BACKGROUND: When confronted with a histologic specimen that is appreciably smaller than the same tissue specimen immediately after acquisition, the Mohs surgeon is faced with two possibilities, namely that the tissue has either shrunken during laboratory processing or that the histologic specimen is incomplete due to the introduction of technical errors during embedding, cutting, or staining of the skin specimen. Because the entire objective of Mohs micrographic surgery is to precisely examine the entire surgical margin of skin specimens, the surgeon must be able to determine that any size discrepancies introduced during laboratory processing are not related to incomplete surgical specimens. Although there are anecdotal suggestions that skin, like other human tissues, undergoes some degree of shrinkage during routine frozen section processing, the exact nature and magnitude of this phenomenon has not been previously investigated. OBJECTIVE: To quantify the degree of tissue shrinkage in Mohs micrographic surgical specimens processed with routine frozen sections and subsequent hematoxylin and eosin staining. METHODS: A total of 117 Mohs surgery patients (135 cutaneous tumors) were prospectively enrolled. The dimensions of initial stage surgical specimens were determined after removal from the patient, after freezing in a mounting medium, after placement on a glass microscopic slide, and after hematoxylin and eosin staining. Statistical analyses were performed in order to determine the significance of any discrepancies in specimen sizes introduced during laboratory processing. RESULTS: Skin specimens processed by frozen section techniques during Mohs micrographic surgery undergo statistically significant alterations in length. On average the measurements of specimens at the conclusion of histologic processing were 11.6% shorter than the measurements of the same specimens obtained immediately after surgical excision. Tissue specimens obtained from the trunk or extremities showed a greater degree of tissue shrinkage (16.3%) than specimens obtained from the head and neck (10.2%). CONCLUSIONS: Our results support anecdotal suggestions that skin specimens do indeed shrink during frozen section processing. By realizing that frozen section specimens can be expected to show some slight degree of shrinkage, the Mohs surgeon can appreciate situations that might allow greater confidence that a smaller specimen is nonetheless representative of the entire lateral and deep surgical margins.

Adult↗
PubMed2001

Prostaglandin endoperoxide H synthase type 1 and type 2 messenger ribonucleic acid in human fetal tissues throughout gestation and in the newborn infant.

OBJECTIVE: We determined the relative abundance of prostaglandin endoperoxide H synthase type 1 and type 2 messenger ribonucleic acid levels in the human fetus and newborn infant. STUDY DESIGN: We used ribonuclease protection assays and normalized values to messenger ribonucleic acid of cyclophilin. Tissues were obtained from all 3 trimesters and in the first 9 days of the newborn period. RESULTS: Prostaglandin endoperoxide H synthase type 1 and type 2 messenger ribonucleic acid is present in every fetal tissue examined (lung, kidney, intestine, heart, brain, and stomach). Kidney and lung demonstrated no changes in the expression of prostaglandin endoperoxide H synthase type 1 messenger ribonucleic acid with gestational age, whereas postnatal levels in lung were one third those in the first trimester (P <.05). A large increase (5-fold to 30-fold; P <.05) occurred throughout gestation for the expression of prostaglandin endoperoxide H synthase type 2 messenger ribonucleic acid in intestine, lung, and kidney, which extended into the newborn period for lung and kidney. CONCLUSIONS: These data imply that the expression of prostaglandin endoperoxide H synthase type 2 messenger ribonucleic acid may be responsible for prostaglandin-related effects and is coordinated in several human fetal tissues in late gestation.

Brain↗
PubMed2001

Kinetic study of the replacement of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs.

Porcine small intestinal submucosa (SIS) was used to replace large, avascular defects in the medial menisci of dogs. Twelve dogs received SIS grafts and 3 dogs were left untreated as controls. Dogs were evaluated at 4, 8, and 12 weeks by means of lameness scoring and ultrasonography. Dogs were sacrificed at 1, 6, or 12 weeks after implantation, and the tissue at the site of meniscal resection was evaluated for gross and histologic appearance, cross-sectional and surface area, and collagen types I and II. The femoral and tibial condyles were assessed for articular cartilage damage. Control dogs were significantly more lame than grafted dogs 8 and 12 weeks after instrumentation. Grafted dogs' replacement tissue appeared meniscal-like when evaluated grossly and ultrasonographically 12 weeks after instrumentation. The amount of replacement tissue was significantly greater in both cross-sectional and surface area for grafted dogs than for controls at all time points. Histologically, the SIS biomaterial could be identified in all grafted dogs at 1 week post-implantation, but in none at 6 weeks post-implantation. Subjectively, grafted dogs' replacement tissue was histologically superior to that of controls with respect to tissue type, organization, and architecture. Collagen types I and II immunoreactivity in grafted menisci were similar to that of normal menisci. Control dogs had significantly more articular cartilage damage than grafted dogs. SIS appears to induce regeneration of meniscal-like tissue in large, avascular meniscal defects in dogs, resulting in superior clinical function and articular cartilage protection compared to ungrafted controls.

Analysis of Variance↗
PubMed2001

Reproducibility and clinical utility of tendon palpation to detect patellar tendinopathy in young basketball players. Victorian Institute of Sport tendon study group.

BACKGROUND: Palpation is an important clinical test for jumper's knee. OBJECTIVES: To (a) test the reproducibility of palpation tenderness, (b) evaluate the sensitivity and specificity of palpation in subjects with clinical symptoms of jumper's knee, and (c) determine whether tenderness to palpation may serve as a useful screening test for patellar tendinopathy. The yardstick for diagnosis of patellar tendinopathy was ultrasonographic abnormality. METHODS: In 326 junior symptomatic and asymptomatic athletes' tendons, palpation was performed by a single examiner before ultrasonographic examination by a certified ultrasound radiologist. In 58 tendons, palpation was performed twice to test reliability. Tenderness to palpation was scored on a scale from 0 to 3 where 0 represented no pain, and 1, 2, and 3 represented mild, moderate, and severe tenderness respectively. RESULTS: Patellar tendon palpation was a reliable examination for a single examiner (Pearson r = 0.82). In symptomatic tendons, the positive predictive value of palpation was 68%. As a screening examination in asymptomatic subjects, the positive predictive value of tendon palpation was 36-38%. Moderate and severe palpation tenderness were better predictors of ultrasonographic tendon pathology than absent or mild tenderness (p<0.001). Tender and symptomatic tendons were more likely to have ultrasound abnormality than tenderness alone (p<0.01). CONCLUSIONS: In this age group, palpation is a reliable test but it is not cost effective in detecting patellar tendinopathy in a preparticipation examination. In symptomatic tendons, palpation is a moderately sensitive but not specific test. Mild tenderness in the patellar tendons in asymptomatic jumping athletes should be considered normal.

Adolescent↗
PubMed2001

The VISA-A questionnaire: a valid and reliable index of the clinical severity of Achilles tendinopathy.

BACKGROUND: There is no disease specific, reliable, and valid clinical measure of Achilles tendinopathy. OBJECTIVE: To develop and test a questionnaire based instrument that would serve as an index of severity of Achilles tendinopathy. METHODS: Item generation, item reduction, item scaling, and pretesting were used to develop a questionnaire to assess the severity of Achilles tendinopathy. The final version consisted of eight questions that measured the domains of pain, function in daily living, and sporting activity. Results range from 0 to 100, where 100 represents the perfect score. Its validity and reliability were then tested in a population of non-surgical patients with Achilles tendinopathy (n = 45), presurgical patients with Achilles tendinopathy (n = 14), and two normal control populations (total n = 87). RESULTS: The VISA-A questionnaire had good test-retest (r = 0.93), intrarater (three tests, r = 0.90), and interrater (r = 0.90) reliability as well as good stability when compared one week apart (r = 0.81). The mean (95% confidence interval) VISA-A score in the non-surgical patients was 64 (59-69), in presurgical patients 44 (28-60), and in control subjects it exceeded 96 (94-99). Thus the VISA-A score was higher in non-surgical than presurgical patients (p = 0.02) and higher in control subjects than in both patient populations (p<0.001). CONCLUSIONS: The VISA-A questionnaire is reliable and displayed construct validity when means were compared in patients with a range of severity of Achilles tendinopathy and control subjects. The continuous numerical result of the VISA-A questionnaire has the potential to provide utility in both the clinical setting and research. The test is not designed to be diagnostic. Further studies are needed to determine whether the VISA-A score predicts prognosis.

Achilles Tendon↗
PubMed2001

Vascular function in alcohol-treated pregnant and nonpregnant mice.

The effect of alcohol on maternal vascular adaptations to pregnancy is unknown. This study was designed to determine the effect of alcohol consumption on nitric oxide-mediated vascular function in mice during pregnancy. Female pregnant or nonpregnant C57BL/6J mice were fed a control diet or a liquid diet of 25% ethanol-derived calories for 13 days (from gestational days 6-18). Phenylephrine vasoconstriction was blunted in pregnancy compared with the nonpregnant state due to enhanced nitric oxide modulation, which was impaired by ethanol exposure. Although the EC50 and maximal responses to methacholine were not different in nonpregnant vs. pregnant mice, the nitric oxide component to methacholine-induced vasorelaxation was greater in the pregnant mice. Interestingly, alcohol affected only the pregnant animals in their response to methacholine. These data indicate that alcohol reduced the nitric oxide modulation of vascular response, which was more pronounced during pregnancy. These studies provide novel information regarding the effects of alcohol on the maternal vascular system during pregnancy and thereby contribute to further understanding of the adverse effects associated with prenatal alcohol exposure.

Animals↗
PubMed2001

Biochemical characterization of cartilage affected by osteochondritis dissecans in the humeral head of dogs.

OBJECTIVE: To determine glycosaminoglycan (GAG) concentration and immunohistochemical staining characteristics of type-I, -II, and -X collagen from cartilage affected by osteochondritis dissecans (OCD) in dogs. ANIMALS: 31 dogs with OCD and 11 clinically normal purpose-bred dogs. PROCEDURE: Cartilage samples were evaluated microscopically, and GAG content was determined. Immunohistochemical staining was performed for type-I, -II, and -X collagen. Sections were subjectively evaluated for location and intensity of staining. RESULTS: Cartilage affected by OCD had a variety of pathologic changes and significantly lower GAG concentrations than did normal cartilage. Normal cartilage had no detectable type-I collagen. For dogs < 9 months of age, cartilage affected by OCD had significantly more type-I collagen but significantly less type-X collagen than did control cartilage. For dogs > 12 months of age, cartilage affected by OCD contained significantly more type-I collagen than did control cartilage. There was a significant negative correlation between immunoreactivity of type-I collagen and that of type-II and -X collagen. A significant positive correlation was found between immunoreactivity of type-II and -X collagen. CONCLUSIONS AND CLINICAL RELEVANCE: Cartilage affected by OCD contains less GAG, more type-I collagen, and less type-X collagen, compared with normal cartilage. A direct correlation between these changes and the etiopathogenesis of OCD was not established.

Animals↗
PubMed2000

Dissimilar immunogenicities of human papillomavirus E7 and adenovirus E1A proteins influence primary tumor development.

Although human papillomaviruses (HPV) and adenoviruses (Ad) both transform cells by expressing functionally related oncogenes (Ad-E1A/E1B; HPV-E7/E6), only HPV are oncogenic in humans. Prior studies have shown that HPV-transformed cells are resistant to NK cell lysis and E7- and E6-specific CTL are inefficiently generated in women with HPV-induced cervical cancer. Therefore, we postulated that the dissimilar oncogenicities of Ad and HPV may be caused by a protective NK and T cell response that is triggered by transformed cells expressing E1A, but not by E7. To test this hypothesis, mice that were either immunologically intact, lacked T cells, or lacked both NK and T cells were challenged with Ad serotype 5 (Ad5)-E1A- or HPV16-E7-transfected tumor cells. E7-expressing tumor cells were resistant to NK cell lysis in vitro and failed to elicit a measurable anti-tumor NK or T cell response in vivo. The concomitant expression of E6 did not change this phenotype. In contrast, E1A-expressing tumor cells were sensitive to NK lysis in vitro and triggered a protective NK and T cell immune response in vivo. These data suggest differences in the capacities of E1A or E7 oncoproteins to trigger protective anti-tumor immune responses may contribute to the dissimilar oncogenicities of Ad and HPV in humans.

Adenovirus E1A Proteins↗
PubMed2000

Adenovirus E1A oncogene expression in tumor cells enhances killing by TNF-related apoptosis-inducing ligand (TRAIL).

Expression of the adenovirus serotype 5 (Ad5) E1A oncogene sensitizes cells to apoptosis by TNF-alpha and Fas-ligand. Because TNF-related apoptosis-inducing ligand (TRAIL) kills cells in a similar manner as TNF-alpha and Fas ligand, we asked whether E1A expression might sensitize cells to lysis by TRAIL. To test this hypothesis, we examined TRAIL-induced killing of human melanoma (A2058) or fibrosarcoma (H4) cells that expressed E1A following either infection with Ad5 or stable transfection with Ad5-E1A. E1A-transfected A2058 (A2058-E1A) or H4 (H4-E1A) cells were highly sensitive to TRAIL-induced killing, but Ad5-infected cells expressing equally high levels of E1A protein remained resistant to TRAIL. Infection of A2058-E1A cells with Ad5 reduced their sensitivity to TRAIL-dependent killing. Therefore, viral gene products expressed following infection with Ad5 inhibited the sensitivity to TRAIL-induced killing conferred by transfection with E1A. E1B and E3 gene products have been shown to inhibit TNF-alpha- and Fas-dependent killing. The effect of these gene products on TRAIL-dependent killing was examined by using Ad5-mutants that did not express either the E3 (H5dl327) or E1B-19K (H5dl250) coding regions. A2058 cells infected with H5dl327 were susceptible to TRAIL-dependent killing. Furthermore, TRAIL-dependent killing of A2058-E1A cells was not inhibited by infection with H5dl327. Infection with H5dl250 sensitized A2058 cells to TRAIL-induced killing, but considerably less than H5dl327-infection. In summary, expression of Ad5-E1A gene products sensitizes cells to TRAIL-dependent killing, whereas E3 gene products, and to a lesser extent E1B-19K, inhibit this effect.

Adenovirus E1A Proteins↗
PubMed2000

Studies of surgical outcome after patellar tendinopathy: clinical significance of methodological deficiencies and guidelines for future studies. Victorian Institute of Sport Tendon Study Group.

Patellar tendinopathy is often treated surgically after failure of conservative treatment but clinical experience suggests that results are not uniformly excellent. The aim of this review was to (i) identify the different surgical techniques that have been reported and compare their success rates, and (ii) critically assess the methodology of studies that have reported surgical outcomes. Twenty-three papers and two abstracts were included in the review. Surgical procedures were categorized and outcomes summarized. Using ten criteria, an overall methodology score was derived for each paper. Criteria for which scores were generally low (indicating methodological deficiency) concerned the type of study, subject selection process and outcome measures. We found a negative correlation between papers' reported success rates and overall methodology scores (r= -0.57, P<0.01). There was a positive correlation between year of publication and overall methodology score (r=0.68, P<0.001). We conclude that study methodology may influence reported surgical outcome. We suggest practical guidelines for improving study design in this area of clinical research, as improved study design would provide clinicians with a more rigorous evidence-base for treating patients who have recalcitrant patellar tendinopathy.

Bias↗
PubMed2000

Patellar tendinopathy in junior basketball players: a controlled clinical and ultrasonographic study of 268 patellar tendons in players aged 14-18 years.

Anterior knee pain is a common presenting complaint amongst adolescent athletes. We hypothesised that patellar tendinopathy may occur at a younger age than is generally recognised. Thus, we studied the patellar tendons in 134 elite 14- to 18-year-old female (n=64) and male (n=70) basketball players and 29 control swimmers (17 female, 12 male) clinically and with ultrasonography. We found that of 268 tendons, 19 (7%) had current patellar tendinopathy on clinical grounds (11% in males, 2% in females). Twenty-six percent of the basketball players' patellar tendons contained an ultrasonographic hypoechoic region. Ultrasonographic abnormality was more prevalent in the oldest tertile of players (17-18 years) than the youngest tertile (14-15.9 years). Of tendons categorised clinically as 'Never patellar tendinopathy', 22% had an ultrasonographic hypoechoic region nevertheless. This study indicates that patellar tendinopathy can occur in 14- to 18-year-old basketball players. Ultrasonographic tendon abnormality is 3 times as common as clinical symptoms.

Adolescent↗
PubMed2000

A review of the bilobed flap's design with particular emphasis on the minimization of alar displacement.

BACKGROUND: The bilobed flap excels in the surgical reconstruction of the distal nose. Unfortunately the aesthetic success of the flap is occasionally limited by the production of distracting alar displacement. OBJECTIVE: To review elements of the bilobed flap's design with a particular emphasis on understanding techniques to minimize distortion of the alar margins. CONCLUSION: With a proper understanding of the bilobed flap's intricate design, the surgeon can anticipate those factors that are most likely to produce temporary or permanent alar asymmetry. Appropriate prospective flap design and meticulous surgical technique can significantly minimize the risk of a poor surgical outcome.

Humans↗
PubMed2000

The changes seen on high-resolution ultrasound in orchitis.

Orchitis and epididymitis are increasingly common lesions encountered in general practice. The clinical diagnosis of inflammation of the testis can be difficult as 10% of neoplasms present acutely with features of inflammation or torsion. The radiological diagnosis is also difficult as the changes seen on ultrasound, whether diffuse or focal, acute or chronic, have to be differentiated from the changes seen with tumours of the testis. The purpose of this review is to describe and illustrate the evolving changes seen in orchitis with reference to the anatomy and pathophysiology of testicular inflammation. We hope that recognition of this pattern may lead to a more confident diagnosis and appropriate management decisions.

Epididymitis↗