Biomedical subjects

John F Madden

Publications and source records attributed to John F Madden.

12 recordsLinked to original sources

PubMed2006

A role for the G12 family of heterotrimeric G proteins in prostate cancer invasion.

Many studies have suggested a role for the members of the G12 family of heterotrimeric G proteins (Galpha12 and Galpha13) in oncogenesis and tumor cell growth. However, few studies have examined G12 signaling in actual human cancers. In this study, we examined the role of G12 signaling in prostate cancer. We found that expression of the G12 proteins is significantly elevated in prostate cancer. Interestingly, expression of the activated forms of Galpha12 or Galpha13 in the PC3 and DU145 prostate cancer cell lines did not promote cancer cell growth. Instead, expression of the activated forms of Galpha12 or Galpha13 in these cell lines induced cell invasion through the activation of the RhoA family of G proteins. Furthermore, inhibition of G12 signaling by expression of the RGS domain of the p115-Rho-specific guanine nucleotide exchange factor (p115-RGS) in the PC3 and DU145 cell lines did not reduce cancer cell growth. However, inhibition of G12 signaling with p115-RGS in these cell lines blocked thrombin- and thromboxane A2-stimulated cell invasion. These observations identify the G12 family proteins as important regulators of prostate cancer invasion and suggest that these proteins may be targeted to limit invasion- and metastasis-induced prostate cancer patient mortality.

Adenocarcinoma↗

PubMed2006

Malignant cystic nephroma.

AIM: To describe a malignant cystic nephroma in an asymptomatic man. METHODS: Case report and review of the literature. RESULTS: A 60 year old white male presented with an incidentally discovered right perirenal mass. An MRI demonstrated a large perinephric encapsulated mass with diffuse heterogeneity. Patient underwent a radical nephrectomy and retroperitoneal node dissection. Histopathological analyses of the resected specimen revealed malignant cystic nephroma. CONCLUSION: This represents the first published report of this rare tumor in an adult patient.

Humans↗

PubMed2005

Renal cryoablation and radio frequency ablation: an evaluation of worst case scenarios in a porcine model.

PURPOSE: Although ablative technologies, including radio frequency (RF) ablation (RFA) and cryoablation (CA), are being used to treat renal masses, complications associated with injury to vital renal structures are not well understood. We investigated these worst case scenarios by deliberately targeting vital renal structures with CA or RFA in a porcine model. MATERIALS AND METHODS: Following surgical exposure of the right kidney in female pigs a cryoneedle or an RF probe was deliberately placed under visual and ultrasound guidance in the renal pelvis (CA in 5 pigs and RFA in 7), major calix (CA and RFA in 5 each) or subsegmental renal vessels (CA in 5 pigs and RFA in 7). Cryo-energy or RF energy was then applied to create a 3 cm lesion. After 10 days the kidneys underwent gross and histological examination for urine and blood extravasation, cell death and injury. Ex vivo retrograde pyelography was performed to evaluate for urinary fistulas. RESULTS: All pigs tolerated the treatment and no procedure related deaths occurred. No significant bleeding was noted. RFA and CA created reproducible lesions and areas of cell death and necrosis. Despite significant intentional injury to the collecting system no urinary fistulas were demonstrated in CA specimens (0 of 15). In contrast, damage to the renal pelvis (4 of 7) by dry (3 of 4) or wet (1 of 3) RFA was associated with a high likelihood of urinary extravasation. CONCLUSIONS: This short-term study demonstrates that CA is safe, effective and not associated with urinary extravasation. In contrast, RFA to the renal pelvis is associated with urinary extravasation. Further studies are needed to support these findings.

Animals↗

PubMed2004

Lysophosphatidic acid promotes survival of androgen-insensitive prostate cancer PC3 cells via activation of NF-kappaB.

BACKGROUND: Dysregulated cell survival contributes to the poor efficacy of many chemotherapeutic regimens for patients with advanced prostate cancer. In this study we examined ability of the lipid growth factor lysophosphatidic acid (LPA), a G protein-coupled receptor (GPCR) ligand, to promote prostate cell survival. METHODS: PC3 cells were used as a model to study mechanisms involved in survival of androgen-insensitive prostate cancer cells. Cell survival was measured by FACS analysis of cell cycle parameters after propidium iodide or annexin V and 7-AAD immunostaining. Activation state of nuclear facor-kappaB (NF-kappaB) was determined biochemically by nuclear translocation and transcriptional activation. Human tissue was analyzed for nuclear expression of NF-kappaB by immunohistochemistry. RESULTS: Molecular dissection of the LPA-regulated PC3 cell survival revealed the sequential phosphorylation of Akt, IkappaB, and transcriptional activation of NF-kappaB. Both Akt and NF-kappaB were required to escape serum deprivation-induced cell death since their inhibition abrogated the LPA-mediated PC3 cell survival. Data from archival human tissue show that NF-kappaB is constitutively activated in prostate cancers, but not in benign prostate tissues. CONCLUSIONS: Targeted disruption of the LPA receptor-Akt-NF-kappaB signaling axis may be effective for the treatment of androgen-insensitive prostate cancer.

Adenocarcinoma↗

PubMed2004

Diagnostic impact of core-needle biopsy on fine-needle aspiration of non-Hodgkin lymphoma.

We retrospectively reviewed 74 fine-needle aspiration (FNA) cases of presumptive non-Hodgkin lymphoma (NHL). All the cases had cytology and core-needle biopsy and 53 cases had concurrent flow cytometric analysis. FNA (cytology and flow cytometry) and core-needle biopsy were evaluated independently. FNA was diagnostic of diffuse large B-cell lymphoma (DLBL) in 25% (13/53) of cases and small B-cell NHL in 15% (8/53) of cases, whereas core-needle biopsy was diagnostic of DLBL in 37% (27/74) of cases and small B-cell NHL in 8% (6/74) of cases. Subclassification of small B-cell NHL was reached in 3/6 cases by core-needle biopsy. Insufficient cases were observed in both FNA (47%; 25/53) and core-needle biopsy (28%; 21/74) groups. With the combination of FNA and core-needle biopsy, diagnostic cases of DLBL increased to 43% (32/74) and insufficient samples were reduced to 16% (12/74). There was no clear advantage in the diagnosis and classification of small B-cell NHL by adding core-needle biopsy to FNA (14%; 10/74). We conclude that core-needle biopsy is a useful adjunct to FNA in the diagnosis of DLBL and shall be encouraged. In small B-cell NHL, core-needle biopsy does not add to the diagnostic ability of FNA. Cases insufficient for diagnosis may be seen in both core-needle biopsy and FNA. A combined approach reduces the number of insufficient cases and is recommended in routine FNA practice.

Algorithms↗

PubMed2004

Pathology of parainfluenza virus infection in patients with congenital immunodeficiency syndromes.

Infection with parainfluenza virus typically produces a mild, self-limited upper respiratory infection. However, parainfluenza infections have become increasingly recognized as a source of severe morbidity and mortality in immunocompromised patients. In this retrospective study we identified 6 patients with congenital immunodeficiency and positive respiratory cultures for parainfluenza virus who died and underwent complete autopsy. Tissues obtained at autopsy were studied using hematoxylin and eosin-stained sections, immunoperoxidase staining for parainfluenza virus, and in selected cases, electron microscopy. All 6 patients exhibited typical cytopathic effects of parainfluenza virus, including giant cell formation, in lung and/or bronchial tissues. Parainfluenza virus infection was also documented by giant cell formation and immunohistochemistry in the pancreas (in 3 of 6 patients) and the kidney or bladder (in 2 of 4 patients). Anti-parainfluenza antibody also specifically reacted with cells in the gastrointestinal tract (in 2 of 4), spleen (in 4 of 6), thymus and/or lymph nodes (in 4 of 4), and small blood vessels in various organs (in 4 of 6). Pancreatic, bladder, colon, and thymic epithelial cell lines were susceptible to experimental infections with clinical isolates of parainfluenza virus type 3 in vitro. Parainfluenza virus infection was serious in patients with congenital immunodeficiencies, contributing directly to death in 5 of the 6 patients studied. Because this virus is capable of infecting tissues in the gastrointestinal and urinary systems as well as in the respiratory tract, body secretions and fluids from each of these locations should be considered potentially infectious.

Cell Line↗

PubMed2003

Bradykinin receptor subtype 1 expression and function in prostate cancer.

Kinins exert multiple pathophysiological functions, including vascular permeability and mitogenesis, by activating their cognate receptors, bradykinin subtype 1 receptor (B1R) and bradykinin subtype 2 receptor (B2R), which belong to the superfamily of G protein-coupled receptors. Tissue-specific expression pattern or contribution of the individual kinin receptors to pathological prostate cell growth is not known. We report here the differential expression of B1R and B2R in human benign and malignant prostate specimens. Whereas B2R is ubiquitously expressed, the B1R is detected only in prostatic intraepithelial neoplasia and malignant lesions and not in benign prostate tissues. Using androgen-insensitive prostate cancer PC3 cells, we show that specific stimulation of endogenous B1R promotes cell growth, migration, and invasion. These findings identify B1R as an early marker for pathological growth of the prostate and suggest its potential utility as a drug target effective for the treatment of prostate cancer.

Biopsy↗

PubMed2003

Liposarcoma presenting as an intraluminal ureteral mass.

An 86-year-old woman with a previous excision of a large retroperitoneal low-grade liposarcoma presented with a 4-month history of persistent left flank discomfort. Workup revealed left hydronephrosis secondary to obstruction, which was caused by a recurrent liposarcoma in the intraluminal ureter. She underwent a left nephroureterectomy for symptomatic palliation. Pathologic study revealed high-grade liposarcoma. Despite negative surgical margins, the tumor rapidly recurred, leading to death only 4 months after surgery. This case highlights the aggressive nature of liposarcoma.

Aged↗

PubMed2002

Laser Doppler flowmetric determination of ureteral blood flow after ureteral access sheath placement.

BACKGROUND AND PURPOSE: The ureteral access sheath has positively impacted ureteroscopy by decreasing operative times and increasing success rates. However, as previous studies have suggested that large-caliber endoscopes may cause ureteral ischemia, concern has been raised about the impact of access sheath insertion on ureteral blood flow. We sought to determine whether the access sheath compromises ureteral blood supply and, if so, causes ischemic damage to the ureter during ureteroscopic procedures. MATERIALS AND METHODS: Using a swine animal model, ureteral blood flow was measured with a laser Doppler flowmeter. Eleven ureteral units were randomized into four study groups: those dilated with 10F-12F, 12F-14F, and 14F-16F access sheaths (N = 3 per group) and an undilated control group (N = 2). Blood flow measurements were obtained from the proximal ureter via laser Doppler flowmetry for 70 minutes at 5-minute intervals. Hemodynamic variability was controlled for through intraoperative heart rate and oxygen saturation monitoring, as well as a second Doppler probe that was placed on the animal's skin, from which readings were also taken every 5 minutes. Results were correlated with histopathologic findings. RESULTS: The control group demonstrated little ureteral blood flow variability over the course of 70 minutes. The study groups that were dilated with sheaths, however, all showed a decrease in ureteral blood flow after access sheath insertion, with the flow in animals dilated with 12F-14F and 14F-16F sheaths dropping below 50% of baseline. This initial drop in blood flow was followed by a gradual increase from nadir toward baseline values over the course of the study. On average, the 14F-16F group reached nadir more quickly and took longer to restore its ureteral blood flow. All animals remained hemodynamically stable throughout the study, showing only minimal variability in heart rate, oxygen saturation, and skin blood flow over the 70-minute experiment. Histologically, there was no evidence of ischemic damage in any of the study groups at 72 hours. CONCLUSIONS: In this animal model, the access sheath does cause a transient decrease in ureteral blood flow. Nonetheless, compensatory mechanisms of the ureteral wall restore blood flow to near-baseline rates and preserve urothelial integrity, suggesting that use of the ureteral access sheath remains a safe adjunct to flexible ureteroscopy. Because the chronic effects of the access sheath have yet to be elucidated, care must be taken in selecting an appropriate-size sheath for each individual case. Preventive measures may be available to help avoid sheath-related ureteral injury in those patients identified as high risk.

Animals↗

PubMed2002

Emergency department personnel use seatbelts almost all the time: what do they know that average Delawareans don't?

A survey was sent to each emergency department in Delaware and each county Emergency Medical Service (EMS) Advanced Life Support (paramedic) service asking seven questions on risk-taking behavior. Within the survey were the following four questions regarding seatbelt use: a) Do you wear a seatbelt while driving? b) Do you require others in your car to wear seatbelts? c) When you are a passenger in a car, do you wear a seatbelt? d) Has the seatbelt law in Delaware impacted your seatbelt use? The three possible responses were "never," "sometimes," and "always." The remaining three questions were confouders and asked about cigarette smoking and driving under the influence of alcohol. Replies were divided into the following job categories: 1) emergency physician (EP), emergency department (ED) physician assistant (PA) or nurse practitioner (NP), 2) emergency nurse, 3) paramedic, or 4) ED clerk, respiratory therapist (RT), or other emergency support personnel. A total of 313 surveys was returned by 78 physicians, NPs and PAs; 115 paramedics; and 115 clerks, RTs, and other support personnel. Overall, 86 percent of respondent stated that they always wear seatbelts with 99 percent of EPs/PAs and NPs responding always. Overall, 83 percent stated that they require others to wear seatbelts in their automobiles. Eighty-four percent wear seatbelts while a passenger in someone else's car. The physician, PA, and NP group had the greatest "always" response rate as compared to the other groups.

Allied Health Personnel↗

PubMed2002

Lithium toxicity: two case reports.

Lithium has many medical and psychiatric uses. These include cluster and migraine headaches, alcoholism, impulsive behavior, and bipolar disorder. Toxicity from lithium can occur by overdose (intentional or accidental) or, more commonly, from alteration in its clearance by the kidney. We present two cases of lithium toxicity. The first is a 57-year-old male who presented with confusion, ataxia, and lethargy. The second case involves a 52-year-old female with bizarre behavior who was unable to care for herself. Both patients received dialysis and recovered without sequelae.

Female↗

PubMedDate not supplied

Anterior rectal wall gastrointestinal stromal tumor presenting clinically as prostatic mass.

Gastrointestinal stromal tumors (GIST) of the anterior rectal wall can present as a prostatic mass, with concomitant obstructive symptoms. Transrectal biopsies of GIST may be misdiagnosed as primary prostatic sarcomas. We report 3 cases of GIST that were initially characterized as prostatic leiomyosarcomas and treated definitively with pelvic exenteration. The correct diagnosis was possible only after immunohistochemical staining for CD117 and was made retrospectively in 2 of 3 cases. Additional therapy with imatinib (Gleevec, Novartis Pharmaceuticals Corporation, East Hanover, NJ), an inhibitor of CD117 tyrosine kinase activity, treated recurrence in one patient and effected complete remission.

Aged↗