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Biomedical subjects

M Conn

Publications and source records attributed to M Conn.

17 recordsLinked to original sources
PubMed2001

Urokinase plasminogen activator amino-terminal peptides inhibit development of the rat ventral prostate.

The plasma membrane urokinase plasminogen activator receptor (uPAR) localizes and enhances activation of pro-uPA. Active uPA, in turn, promotes increased degradation of the extracellular matrix (ECM) by activation of plasminogen. uPAR binds to ECM molecules and integrins, which can affect cellular adhesion, signal transduction, and gene regulation. The current study examines the expression and function of uPAR in developing rat ventral prostates (VPs). We report that newborn VPs express uPAR mRNA and protein. In addition, the function of uPAR-bound uPA during in vitro prostatic development was studied by adding recombinant peptide competitive inhibitors of uPA-uPAR binding. Newborn VP explants were cultured in serum-free media for one week with 10(-8) M testosterone plus chimeric peptides containing a human immunoglobulin G Fc domain and either human uPA amino acids 1-138 (hu-uPA 1-138) as a control or mouse uPA amino acids 1-138 (mo-uPA 1-138) or 1-48 (mo-uPA 1-48). Hu-uPA 1-138-treated VPs underwent normal ductal branching morphogenesis and tissue differentiation. In contrast, VPs treated with mo-uPA 1-138 or mo-uPA 1-48 displayed a dose-dependent perturbation of ductal branching. Differentiation of both epithelial and mesenchymal tissues was also impaired. Mo-uPA 1-48-treated VPs contained significantly more apoptotic cells. These observations suggest that disruption of uPA binding to uPAR results in a retardation of the development of newborn VPs.

Animals↗
PubMed2000

Development of the school organisational health questionnaire: a measure for assessing teacher morale and school organisational climate.

BACKGROUND: A growing body of empirical evidence suggests that organisational factors are more important than classroom specific issues in determining teacher morale. Accordingly, it is necessary to have available measures that accurately assess morale, as well as the organisational factors that are likely to underpin the experience of morale. AIM: Three studies were conducted with the aim of developing a psychometrically sound questionnaire that could be used to assess teacher morale and various dimensions of school organisational climate. SAMPLE: A total of 1,520 teachers from 18 primary and 26 secondary schools in the Australian state of Victoria agreed to participate in three separate studies (N = 615, 342 and 563 in Studies 1, 2 and 3, respectively) that were used to develop the questionnaire. The demographic profile of the teachers was similar to that found in the Department as a whole. METHOD: All teaching staff in the participating schools were asked to complete a self-report questionnaire as part of the evaluation of an organisational development programme. RESULTS: A series of exploratory and confirmatory factor analyses were used to establish the questionnaire's factor structure, and correlation analyses were used to examine the questionnaire's convergent and discriminant validity. CONCLUSIONS: The three studies resulted in the 54-item School Organisational Health Questionnaire that measures teacher morale and 11 separate dimensions of school organisational climate: appraisal and recognition, curriculum coordination, effective discipline policy, excessive work demands, goal congruence, participative decision-making, professional growth, professional interaction, role clarity, student orientation, and supportive leadership.

Adolescent↗
PubMed2000

Results of liver transplantation for nodular regenerative hyperplasia.

Liver transplantation has been performed in individuals with a pretransplant clinical diagnosis of cirrhosis but with nodular regenerative hyperplasia histologically. The purpose of this report is to investigate the results of liver transplantation in patients proven to have nodular regenerative hyperplasia post-transplant. A retrospective review was undertaken of four patients who underwent liver transplantation with a histologic diagnosis of nodular regenerative hyperplasia. All were felt to be cirrhotic on clinical grounds. Final histology of the explanted liver was confirmed by a single pathologist. Their ages ranged from 39 to 54 years, and three of the four were male. Three had pretransplant needle liver biopsies, two percutaneous and one transjugular. All revealed nonspecific reactive changes. Ultrasound and MRI were interpreted as consistent with cirrhosis in four of four and three of four cases, respectively. Portal vein flow was hepatopedal in three and absent in one. Pretransplant clinical characteristics and frequency were as follows: bleeding varices two, clinical ascites three, encephalopathy three, and impaired hepatic synthetic function two. All four patients underwent successful liver transplantation. There were no episodes of acute rejection. All are alive and well with normal graft function 2 to 4 years post-transplant. We conclude the following. 1) Patients with clinical end-stage liver disease due to underlying nodular regenerative hyperplasia can successfully undergo transplantation. 2) Nodular regenerative hyperplasia can present with signs and symptoms of liver failure, is difficult to diagnose by needle biopsy, and can be difficult to discriminate clinically from cirrhosis. 3) Although each case must be individually evaluated transplantation may be the optimal therapy in patients presenting with complications of liver failure.

Adult↗
PubMed1997

Inhibition of prostate cancer neovascularization and growth by urokinase-plasminogen activator receptor blockade.

Binding of the serine protease urokinase (u-PA) to its receptor on tumor cell surfaces facilitates proteolysis and tumor invasion. We undertook this study to determine whether the role of u-PA in prostate cancer induced angiogenesis and secondary tumor growth by developing a homologous, immunocompetent in vivo model in which the tumors cells secrete an inhibitor of the murine u-PA receptor. A mutant recombinant murine u-PA that retains receptor binding but not proteolytic activity was made by PCR mutagenesis. Mutant u-PA and a reporter gene pRK luciferase were transfected and stably expressed in the highly metastatic rat Dunning MAT-LyLu prostate cancer cell line. Several clones expressing mutant u-PA and luciferase were identified by Western blotting, plasminogen zymography, and reverse transcription-PCR. One of these clones, 5C4, was injected s.c. into Copenhagen rats. Compared to animals injected with clones expressing pRK luciferase alone, tumors in animals injected with 5C4 cells were significantly smaller. Moreover, there were fewer lung micrometastases in the 5C4 animals. Primary tumor angiogenesis was measured by microvessel quantification of tissue stained with antibodies against von Willebrand factor. Mean microvessel density in 5C4 tumors was 4.3-fold lower than that in animals with tumors derived from the control tumor cell line (P < 0.0001). Significant inhibition of tumor growth was also observed for two additional MAT-LyLu cell lines expressing mutant u-PA. These findings suggest that cell surface u-PA contributes to prostate cancer growth by enhancing angiogenesis.

Animals↗
PubMed1995

Conventional wisdom is a poor predictor of the relationship between discipline policy, student misbehaviour and teacher stress.

Will an effective discipline policy improve student misbehaviour and result in a reduction of teacher stress? It is commonly believed that student misbehaviour is a major cause of teacher stress, and that the degree of student misbehaviour is reflected in student suspension rates. Moreover, it is believed that student misbehaviour can be reduced by improving a school's discipline policy through the collaborative efforts of whole school communities. As a result of growing concern about student misbehaviour and teacher stress, a Whole School Approach to Discipline and Student Welfare programme was implemented throughout the Australian state of Victoria. This paper reports on the evaluation studies that were conducted to assess the effectiveness of the programme and examine the assumptions which underpinned its implementation. Data were obtained from 4,072 primary and secondary school teachers. Although longitudinal analyses suggested that the programme was effective in reducing teacher stress, there was no mean change in student misbehaviour. Structural equation analyses showed that there was little relationship between a school's discipline policy and the perceived level of student misbehaviour. It was also found that student suspension rates were not related to student misbehaviour, but could be predicted on the basis of a school's discipline policy and the self-esteem of teachers. Two and three wave causal analyses also demonstrated the problems associated with using cross-sectional research to support major policy decisions. Overall, these studies showed that there is little point in trying to reduce teacher stress by reducing student misbehaviour. Rather, it is more appropriate to develop a supportive organisational climate that enables teachers to cope with the student misbehaviour that confronts them.

Adolescent↗
PubMed1993

Localization of cytomegalovirus antigens in liver allografts over time.

Cytomegalovirus (CMV) hepatitis is a common and serious complication of orthotopic liver transplantation. Immunohistochemical studies are the most sensitive methods of diagnosis. We compared immunoperoxidase staining with monoclonal antibodies to CMV immediate early and early antigens with routine hematoxylin-eosin stain. Eleven of 140 liver allograft recipients at our institution had CMV hepatitis identified by hematoxylin-eosin stain on biopsy specimens. We stained serial sections of all previous biopsy specimens and one post-ganciclovir biopsy specimen (when available) from each of these patients. One or both monoclonal antibodies confirmed the original hematoxylin-eosin stain diagnoses. Cytomegalovirus was detected in earlier, hematoxylin-eosin stain-negative biopsy specimens in seven of 11 patients. Detection of immediate early antigen often preceded that of early antigen. Earlier biopsy specimens demonstrated less positive staining, which become more extensive closer in time to the hematoxylin-eosin stain-positive biopsy specimens. Sinusoidal cells became positive earlier than hepatocytes. In one patient occult CMV antigens persisted in biopsy specimens following ganciclovir treatment. We conclude that (1) immunohistochemical staining for CMV antigens can result in earlier detection of viral infection, which may lead to earlier, more effective treatment; (2) CMV infection and antigen expression is focal, requiring extensive examination for diagnosis; (3) extent of occult infection may indicate the extent of active infection in the organ as a whole; (4) most CMV hepatitis begins with infection of sinusoidal lining cells as a result of hematogenous spread from within the allograft or from systemic viremia; and (5) posttreatment biopsy specimens may be more sensitive than resolution of serum liver enzyme abnormalities in evaluating the success of ganciclovir therapy.

Antigens, Viral↗
PubMed1992

Simultaneous laparotomy and endoscopy for control of bleeding gastric ulcerations after liver transplantation without enterotomy.

Treatment of gastric peptic ulcerations, which requires both medical and surgical coordination in its management, is a complex subject. Despite advances in the medical therapy of ulcers, medications have little impact on the course of bleeding peptic ulceration. Newer endoscopic techniques of injection with adrenaline or alcohol, heater probes, and vicaps electrodes have controlled bleeding in many patients. Still, a subset of patients remains who will require surgical interventions with gastrotomy and oversewing of the ulcer crater. We describe a new technique for management of the acute gastric ulcer bleeding that avoids gastrotomy and potential contamination in the post-transplant patient.

Esophageal and Gastric Varices↗
PubMed1991

The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors.

The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis.

Acute Disease↗
PubMed1991

Preoperative evaluation of the patient with liver disease.

Patients with underlying liver disease have an increased surgical risk. Prediction of surgical risk is based on the degree of liver dysfunction, the type of surgery, and the preoperative clinical status of the patient. The medical consultant must determine the type of liver disease (acute or chronic) and the degree of impairment of liver function (based on physical examination and laboratory data). Any abnormalities should be corrected prior to surgery. Elective surgery should be postponed in patients with decompensated cirrhosis (class B and C) and acute hepatitis until the patient improves. The consultant internist's care of the patient should continue during the early postoperative course to monitor any deterioration in liver function.

Anesthesia↗
PubMed1984

Microaggregation of the gonadotropin-releasing hormone-receptor: relation to gonadotrope desensitization.

Desensitization of the pituitary gonadotrope was examined using perifusion of immobilized dispersed cells. Specifically, a relatively brief (20 min) pulse of GnRH was shown to result in markedly reduced release of LH in response to subsequent administration of the releasing hormone. Derivatives of cAMP exerted neither an inhibitory nor a stimulatory effect on desensitization. Nonreceptor mediated secretagogues (phorbol dibutyrate and melittin) promoted gonadotropin release without desensitizing pituitary cells indicating that release and desensitization are dissociable. However, conditions that promote GnRH receptor-receptor cross-linking did lead to reduced GnRH-responsiveness, even when the receptor was occupied by an antagonist. Cells were perifused with a conjugate consisting of two dimers of a pure GnRH-antagonist (D-pGlu1-D-Phe2-D-Trp3-D-Lys6-GnRH) attached to cross-reacting antibody. The antagonist conjugate, now able to cross-link (microaggregate) GnRH receptors, is converted to an agonist. In the present work we show that the conjugate stimulates desensitization in addition to release of LH. This observation suggests that microaggregation is the final step common to both pathways, on the one hand leading to Ca2+ mobilization and release of LH, and on the other, leading to Ca2+ independent receptor-mediated desensitization.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Effects of two procedural modifications of the frequency of false-alarm responses during pure-tone threshold determination.

In normal-hearing young adults without tinnitus, HTLs were collected using 5-db steps, and false alarms (FA's) noted, at octaves from .25-8 kc/s either in quiet or in a white noise background set at 15 db sensation level for each S. In Exper. I (N:10), the ascending and descending modes did not yield significantly different numbers of FA's in quiet; in noise, FA's increased significantly vs the quiet condition in the ascending but not in the descending modes, while in noise, furthermore, FA's increased significantly for the ascending vs the descending mode. In a similar Exper. II (N:10), the 4 combinations (single- and pulsed-tone presentations, ascending and descending modes) showed that FA's were significantly fewest with a descending, pulsed-tone technique. It was recommended that when FA's pose a problem when using the ascending mode, single-tone technique (ASHA guidelines), the clinician change to the descending, pulse-tone technique to reduce FA's by increasing the stimulus certainty under difficult listening circumstances.

Audiometry↗
PubMed1978

Chronic inhibition of brain protein synthesis after portacaval shunting. A possible pathogenic mechanism in chronic hepatic encephalopathy in the rat.

We investigated the effects of chronic portacaval shunting, with or without additional ammonia loading, on brain protein synthesis in unanesthetized rats by continuous intravenous infusion of 3H-lysine (10 mumoles per gram, 0.2 muCi/mumole). Lysine was incorporated into forebrain proteins at a rate of 1.6 nanomoles/mg protein per hour in sham-operated controls, but at a rate of only 0.83 nanomoles/mg protein per hour (p less than 0.001) in paired rats 6 to 8 weeks after construction of a portacaval shunt. An acute load of ammonium acetate in portacaval-shunted animals further decreased the rate of lysine incorporation into forebrain proteins. Chronic inhibition of protein synthesis may play a role in the pathogenesis of chronic portacaval encephalopathy.

Ammonia↗
PubMed1977

Progesterone-binding components of chick oviduct. Biochemical characterization of purified oviduct progesterone receptor B subunit.

A number of physical and chemical properties of pure hen oviduct progesterone receptor B subunit have been determined. The molecule consists of a single polypeptide chain with a molecular weight of 115,000 g/mol as determined by gel filtration in the presence of 6 M guanidine hydrochloride and by gel electrophoresis in sodium dodecyl sulfate. The labeled subunit has retained the biologically important properties which it displayed in cruder preparations: it binds to nuclei (Kd = 1 X 10(-9) M) and chromatin (Kd = 1.5 X 10(-9) M) but does not bind to DNA. Reaction of the purified subunit with dansyl (5-dimethylaminonaphthalene-1-sulfonyl) chloride revealed a single NH2-terminal lysine. The amino acid composition has been determined and has been shown to be distinct from that of other steroid-binding proteins and consistent with the known properties of the molecule. In addition, no evidence for carbohydrate or phosphorylated amino acids was observed. The protein contains about 12% alpha helix as determined by circular dichroism. The ultraviolet spectrum of intact steroid receptor complexes revealed that the purified subunit had no pyridine nucleotide cofactor or nucleic acid, and that each receptor molecule contains a single hormone binding site. Electron microscopic analysis confirms the prolate-ellipsoid shape of the protein, with a long axis of 114 A. The purified protein isolated as described in a companion paper is shown here to have the characteristics of the crude receptor subunit B. Due to the apparent role in the hormone response, this protein has been named progestophilin B.

Amino Acids↗
PubMed1975

A spondee list for determining speech reception threshold without prior familiarization.

The purpose of this investigation was to select a list of spondees from the CID W-1 spondee word list that eliminates the need for familiarization but produces spondee thresholds equivalent to those obtained with familiarization. Forty-eight subjects with normal hearing responded to familiarized and unfamiliarized spondee words at their familiarized spondee threshold levels. Spondee words that were correctly identified most often without prior familiarization or whose correct response rates were least altered by familiarization were selected for the final list. Seventeen words were selected from the criteria of the present study; two of these words were excluded from the final list since they did not fall within the recommended 4-dB range. The 15 remaining spondee words without familiarization produced spondee thresholds equivalent to the entire CID W-1 list with familiarization in a direct comparison of the two lists in 20 subjects with normal hearing.

Adolescent↗