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Biomedical subjects

M J Cross

Publications and source records attributed to M J Cross.

At least 37 records · Page 2Linked to original sources
PubMed2000

G protein-coupled receptor-mediated mitogen-activated protein kinase activation through cooperation of Galpha(q) and Galpha(i) signals.

G protein-coupled receptors (GPCRs) have been shown to stimulate extracellular regulated kinases (ERKs) through a number of linear pathways that are initiated by G(q/11) or G(i) proteins. We studied signaling to the ERK cascade by receptors that simultaneously activate both G protein subfamilies. In HEK293T cells, bradykinin B(2) receptor (B(2)R)-induced stimulation of ERK2 and transcriptional activity of Elk1 are dependent on Galpha(q)-mediated protein kinase C (PKC) and on Galpha(i)-induced Ras activation, while they are independent of Gbetagamma subunits, phosphatidylinositol 3-kinase, and tyrosine kinases. Similar results were obtained with m(1) and m(3) muscarinic receptors in HEK293T cells and with the B(2)R in human and mouse fibroblasts, indicating a general mechanism in signaling toward the ERK cascade. Furthermore, the bradykinin-induced activation of ERK is strongly reduced in Galpha(q/11)-deficient fibroblasts. In addition, we found that constitutively active mutants of Galpha(q/11) or Galpha(i) proteins alone poorly stimulate ERK2, whereas a combination of both led to synergistic effects. We conclude that dually coupled GPCRs require a cooperation of Galpha(i)- and G(q/11)-mediated pathways for efficient stimulation of the ERK cascade. Cooperative signaling by multiple G proteins thus might represent a novel concept implicated in the regulation of cellular responses by GPCRs.

Animals↗
PubMed2000

Tyrosine 766 in the fibroblast growth factor receptor-1 is required for FGF-stimulation of phospholipase C, phospholipase D, phospholipase A(2), phosphoinositide 3-kinase and cytoskeletal reorganisation in porcine aortic endothelial cells.

Fibroblast growth factor-mediated signalling was studied in porcine aortic endothelial cells expressing either wild-type fibroblast growth factor receptor-1 or a mutant receptor (Y766F) unable to bind phospholipase C-(&ggr;). Stimulation of cells expressing the wild-type receptor resulted in activation of phospholipases C, D and A(2) and increased phosphoinositide 3-kinase activity. Stimulation of the wild-type receptor also resulted in stress fibre formation and a cellular shape change. Cells expressing the Y766F mutant receptor failed to stimulate phospholipase C, D and A(2) as well as phosphoinositide 3-kinase. Furthermore, no stress fibre formation or shape change was observed. Both the wild-type and Y766F receptor mutant activated MAP kinase and elicited proliferative responses in the porcine aortic endothelial cells. Thus, fibroblast growth factor receptor-1 mediated activation of phospholipases C, D and A(2) and phosphoinositide 3-kinase was dependent on tyrosine 766. Furthermore, whilst tyrosine 766 was not required for a proliferative response, it was required for fibroblast growth factor receptor-1 mediated cytoskeletal reorganisation.

Animals↗
PubMed1999

Outcomes after hip or knee replacement surgery for osteoarthritis. A prospective cohort study comparing patients' quality of life before and after surgery with age-related population norms.

OBJECTIVE: To compare the health-related quality of life of people with osteoarthritis before and after primary total hip and knee replacement surgery with that of the general Australian population. DESIGN: A prospective cohort study. SETTING: Three Sydney hospitals, public and private. PARTICIPANTS: Patients with osteoarthritis undergoing primary total hip (n = 59) and knee (n = 92) joint replacement surgery. MAIN OUTCOME MEASURE: Medical Outcomes Study Short Form (SF-36) scores before and 12 months after joint replacement surgery (compared with population norms). RESULTS: Patients in each age group showed a significant improvement in health-related quality of life after joint replacement surgery in most scales of the SF-36, particularly physical function, role physical and bodily pain. SF-36 scores for the 42 hip-replacement patients aged 55-74 years improved to equal or exceed the population norm on all scales. SF-36 scores of the 52 knee replacement patients aged 55-74 years improved, but physical function and bodily pain scores remained significantly worse than the population norm. SF-36 scores for both hip (n = 17) and knee (n = 40) replacement patients aged 75 years and over improved significantly, becoming similar to population norms for this age group. CONCLUSIONS: Total hip or knee replacement for osteoarthritis significantly improves patient health and well-being at 12 months after surgery. Age alone should not be a barrier to surgery.

Aged↗
PubMed1999

The intercruciate band of the human knee. An anatomical and histological study.

Thirty cruciate ligaments were retrieved from either cadavers or limbs which had been amputated. Each specimen was sectioned and stained to demonstrate the presence of collagen, nerves and vessels. All 30 specimens contained an interconnecting band of collagen fibres between the anterior and posterior cruciate ligaments. Vascular structures were present in all specimens and nerve fibres were identified in 26 (86%). We have called this structure the 'intercruciate band'. The anterior and posterior cruciate ligaments should no longer be thought of in isolation, but together as a 'cruciate complex'.

Anterior Cruciate Ligament↗
PubMed1998

Operative reconstruction after transverse rupture of the tendons of both peroneus longus and brevis. Surgical reconstruction by transfer of the flexor digitorum longus tendon.

Rupture of the tendons of both peroneus longus and peroneus brevis results in considerable disability. We have performed transfer of flexor digitorum longus (FDL) to peroneus brevis in two patients with lateral instability of the hindfoot due to chronic transverse tears of both tendons for which end-to-end repair was not possible. Both patients had excellent function when reviewed after eight and six years, respectively, with no symptoms. CT showed a normal appearance of the FDL in both patients, but the peroneal muscles looked abnormal. Transfer of the FDL provides a reliable solution to lateral instability of the hindfoot resulting from loss of function of both peronei.

Ankle↗
PubMed1997

Inhibition of phospholipid signalling and proliferation of Swiss 3T3 cells by the wortmannin analogue demethoxyviridin.

Growth factors and certain oncogenes activate a range of phospholipid-mediated signal transduction pathways resulting in cell proliferation. Demethoxyviridin (DMV), a structural analogue of wortmannin and recently reported as a potent inhibitor of phosphoinositide-3-kinase, inhibited bombesin plus insulin-stimulated increase in cell number in Swiss 3T3 cells, a model of cell proliferation. The drug produced cytostatic effects at concentrations below 1 microM and cytotoxic effects at 10 microM. In intact Swiss 3T3 cells DMV inhibited insulin-stimulated PI 3- and 4-kinases and bombesin-stimulated phospholipases C, D and A2 in the nanomolar range. DMV also inhibited bombesin-stimulated tyrosine phosphorylation of a range of proteins at nM concentrations. This study shows that DMV inhibited multiple stimulated signalling pathways which lead to increased Swiss 3T3 cell proliferation. A stable analogue of DMV may have chemotherapeutic potential.

3T3 Cells↗
PubMed1997

Role and regulation of phospholipase D activity in normal and cancer cells.

PLD is regulated by the small GTP binding proteins Rho and Arf, though predominantly by the latter. The PA product of PLD activation is an activator of Rho-regulated actin stress fibre formation and in invasive cells of MMP-9 synthesis and activation. Together this may explain the increased invasion of cells in response to PA.

ADP-Ribosylation Factors↗
PubMed1996

Stimulation of actin stress fibre formation mediated by activation of phospholipase D.

BACKGROUND: Agonist-stimulated phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine, generating the putative messenger phosphatidate (PA). Proposed functions for PA, and hence for PLD, include kinase activation, the regulation of small molecular weight GTP-binding proteins, actin polymerization and secretion. It has not been possible to define a physiological function for PLD activation as it is generally stimulated together with other signalling pathways, such as those involving phospholipases A2 and C, phosphatidylinositide (PI) 3-kinase and the p21(ras)/mitogen-activated protein (MAP) kinase cascade. RESULTS: We report that, in porcine aortic endothelial (PAE) cells, lysophosphatidic acid (LPA) stimulated PLD activity and rapidly generated PA in the absence of other phospholipase, PI 3-kinase or MAP kinase activities. PLD activation was controlled by a tyrosine kinase-regulated pathway. LPA also stimulated actin stress fibre formation, but was inhibited by butan-1-ol; the alcohol also reduced the accumulation of PA. The addition of PA to cells did not stimulate PLD activity, but did cause stress fibre formation in a manner that was insensitive to butan-1-ol. Stimulation of stress fibre formation by LPA and PA was sensitive to genistein, and was inhibited by micro-injection of the Rho-inhibiting C3 exotoxin into PAE cells. CONCLUSIONS: This study provides the first clear demonstration of a physiological role for PLD activity. In PAE cells, the stimulation of actin stress fibre formation was a consequence of PA generation and, therefore, PLD activation. The results suggest that PA generation is upstream of Rho activation, and imply a role for PLD in the regulation of Rho-mediated pathways.

Actins↗
PubMed1995

Wortmannin and its structural analogue demethoxyviridin inhibit stimulated phospholipase A2 activity in Swiss 3T3 cells. Wortmannin is not a specific inhibitor of phosphatidylinositol 3-kinase.

Wortmannin and its structural analogue demethoxyviridin (DMV) have been reported to be specific inhibitors of phosphatidylinositol 3-kinase activity. Here we report that these compounds are not as selective as assumed and demonstrate inhibition of bombesin-stimulated phospholipase A2 activity by both wortmannin and DMV with an IC50 (2 nM) which is slightly more potent than the inhibition of insulin-stimulated phosphatidylinositol 3,4,5-trisphosphate generation in these cells (approximately 10nM). While it has not been possible to fully block in vitro phospholipase A2 activity with wortmannin, inhibition cannot be a consequence of inhibition of PI 3-kinase activity since bombesin fails to generate 3-phosphorylated lipids in the intact cell. Therefore, while wortmannin is indeed a PI 3-kinase inhibitor, it is not as specific as previously reported, and experimental conclusions based solely on its use should be treated with caution.

3T3 Cells↗
PubMed1995

Stereotactic breast biopsy as an alternative to open excisional biopsy.

BACKGROUND: Health care cost continues to play a dominant role in our society. Technological advances are expensive, with the possible exception of stereotactic breast biopsy. We must learn other alternatives that give the same diagnostic accuracy at lower cost. The intention of this study was to find other acceptable alternatives to open excisional breast biopsies. METHODS: Patients were referred to Baylor University Medical Center between May 1990 and June 1992 for stereotactic breast biopsy of nonpalpable mammographic abnormalities. Before stereotactic biopsy, lesions were categorized into low or high suspicion for malignancy based on screening mammography. Slides were reviewed by a pathologist and the histological diagnosis was compared with mammographic characterization. Benign histology confirming the low-suspicion mammographic abnormality demonstrated mammographic and histologic correlation. Mammographic follow-up was recommended. RESULTS: Two hundred twenty-five women underwent 250 stereotactic breast biopsies. Malignancy was diagnosed in 47 patients; the remaining 203 lesions were benign on pathological examination and are being followed regularly. Seventy-eight percent of the lesions were characterized as low suspicion for malignancy, and 22% were characterized as high suspicion. The average cost savings per lesion using stereotactic biopsy was $1,629. CONCLUSION: Stereotactic breast biopsy is an acceptable, less expensive alternative to open excisional biopsy for diagnosing nonpalpable mammographic findings.

Adult↗
PubMed1995

A specific radioimmunoassay for the determination of morphine-6-glucuronide in human plasma.

A specific antiserum for morphine-6-glucuronide (M6G) has been raised in a rabbit in response to immunization with a novel hapten:protein conjugate (N-aminobutylnormorphine-6-glucuronide-thyroglobulin). Cross-reactivity with morphine and structurally related compounds was found to be negligible as expected from the nature of this immunogen. Using this antiserum, a simple, rapid and robust radioimmunoassay (RIA) has been developed for determination of M6G in samples of human plasma. The assay has a sensitivity of 0.05 ng/mL using 100 microL sample volumes and affords complete recovery of M6G over the range 2-200 ng/mL. The presence of morphine or morphine-3-glucuronide at concentrations up to 100 times the levels of M6G did not result in any measurable interference. Close agreement was obtained between M6G results obtained using the RIA and a specific high-performance liquid chromatography assay. This RIA offers an attractive alternative to existing methods for the determination of M6G in human plasma and will facilitate further metabolic and pharmacokinetic studies of morphine and M6G in the clinical setting.

Humans↗
PubMed1993

New horizons in the diagnosis and treatment of breast cancer using magnetic resonance imaging.

A new nuclear magnetic resonance imaging (MRI) technique, Rotating Delivery of Excitation Off-resonance (RODEO), has been developed to assist surgeons in the diagnosis and treatment of breast cancer. A nonrandomized, prospective study of 100 patients with a high suspicion of breast cancer was conducted; these patients were examined by RODEO and conventional breast imaging, including mammography. Forty-one breasts were removed by mastectomy; each pathologic specimen was examined by sectional analysis. This study was undertaken to determine the extent that RODEO can aid in detecting breast tumors (including multicentric disease) and in evaluating candidates for conservative breast surgery. RODEO detected 85 pathologically confirmed lesions, 64 of which proved to be malignant. RODEO had a sensitivity of 95%, compared with a sensitivity of 58% for conventional imaging. More study is needed to determine distinguishing MRI characteristics that are suspicious for malignancy. RODEO may be used clinically to assess multicentricity and response to chemotherapy.

Breast Neoplasms↗
PubMed1993

Laparoscopic-directed small bowel resection for jejunal diverticulitis with perforation.

The authors report a case in which an 87-year-old woman underwent diagnostic laparoscopy for abdominal pain of unknown etiology. Jejunal diverticulosis was discovered with diverticulitis and perforation into the mesentery. Visualization of the appendix, ovaries, uterus, colon, and liver ruled out additional pathology. The disease was serious enough that resection of the involved jejunum was necessary. With the aid of the laparoscope, the incision was directed nearer to the area of the disease. A 5 cm left upper quadrant transverse incision was made, allowing removal of perforation and the diseased bowel. Primary resection and anastomosis were performed. This case sets a precedence for use of exploratory diagnostic laparoscopy and particularly small bowel resection for symptomatic diverticulitis. The authors believe that this technique results in less postoperative pain, allowing for a prompt recovery with minimal morbidity and mortality, particularly in the elderly population.

Aged↗
PubMed1992

Surgical treatment of radiation enteritis.

Radiation enteritis is a progressive, disease process that causes intestinal fibrosis and obliterative endarteritis, which results in significant morbidity and mortality. The authors' clinical experience involving 20 patients over a 22-year period from 1967 through 1989 who underwent various surgical procedures to alleviate chronic symptoms secondary to radiation enteritis is described. Eight men and 12 women with a mean age of 52 years (24 to 81 years) underwent a total of 27 procedures for complications of radiation enteritis. Radiation therapy was delivered for treatment of gynecologic malignancies (55%), colorectal cancer (20%), prostate malignancies (10%), and others (15%). The mean average dose of radiation delivered was 5,514 rads with a range of 2,613 to 7,000 rads. The interval from radiation treatment to time of surgery averaged 9 years. Operative procedures consisted of 12 resection and primary anastomosis procedures and 15 resections with stoma creation. Formation of a stoma was used in patients with more severe disease. The 30-day operative mortality was 0% and morbidity was 55%. There were no anastomotic leaks or intra-abdominal abscesses. The authors conclude that resection and primary anastomosis can safely be performed in selected patients but that judicious use of stoma formation can avoid major mortality and morbidity associated with surgery in this setting.

Adult↗
PubMed1990

Patellofemoral malalignment: a report of 68 cases treated by proximal and distal patellofemoral reconstruction.

A series of 68 knees were reviewed retrospectively at an average of 56 months following surgical treatment for patellar dislocation and subluxation. Fifty-three knees in 48 patients were assessed both subjectively by questionnaire and objectively by examination, and 15 knees were evaluated by questionnaire only. All cases were treated by a proximal and distal reconstruction as described by Trillat (1964). The surgery was performed by one surgeon (MC) and reviewed independently (DW). The results were excellent in 48 knees (71 per cent), good in 12 (17 per cent) and poor in 8 (12 per cent). In no patient had there been any further episodes of dislocation. We consider this a straightforward procedure producing consistent correction of patellofemoral instability with a low morbidity.

Adolescent↗