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Biomedical subjects

D M Rose

Publications and source records attributed to D M Rose.

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

Radiofrequency ablation of 231 unresectable hepatic tumors: indications, limitations, and complications.

BACKGROUND: Radiofrequency ablation (RFA) is increasingly used for the local destruction of unresectable hepatic malignancies. There is little information on its optimal approach or potential complications. METHODS: Since late 1997, we have undertaken 91 RFA procedures to ablate 231 unresectable primary or metastatic liver tumors in 84 patients. RFA was performed via celiotomy (n = 39), laparoscopy (n = 27), or a percutaneous approach (n = 25). Patients were followed with spiral computed tomographic (CT) scans at 1 to 2 weeks postprocedure and then every 3 months for 2 years. RESULTS: Intraoperative ultrasound (IOUS) detected intrahepatic disease not evident on the preoperative scans of 25 of 66 patients (38%) undergoing RFA via celiotomy or laparoscopy. In 38 of 84 patients (45%), RFA was combined with resection or cryosurgical ablation (CSA), or both. RFA was used to treat an average of 2.8 lesions per patient, and the median size of treated lesions was 2 cm (range, 0.3-9 cm). The average hospital stay was 3.6 days overall (1.8 days for percutaneous and laparoscopic cases). Ten patients underwent a second RFA procedure (sequential ablations) and, in one case, a third RFA procedure for large (one patient), progressive (seven patients), and/or recurrent (three patients) lesions. Seven (8%) patients had complications: one skin burn; one postoperative hemorrhage; two simple hepatic abscesses; one hepatic abscess associated with diaphragmatic heat necrosis following sequential percutaneous ablations of a large lesion; one postoperative myocardial infarction; and one liver failure. There were three deaths, one (1%) of which was directly related to the RFA procedure. Three of the complications, including one RFA-related death, occurred after percutaneous RFA. At a median follow-up of 9 months (range, 1-27 months), 15 patients (18%) had recurrences at an RFA site, and 36 patients (43%) remained clinically free of disease. CONCLUSIONS: Celiotomy or laparoscopic approaches are preferred for RFA because they allow IOUS, which may demonstrate occult hepatic disease. Operative RFA also allows concomitant resection, CSA, or placement of a hepatic artery infusion pump, and isolation of the liver from adjacent organs. Percutaneous RFA should be reserved for patients at high risk for anesthesia, those with recurrent or progressive lesions, and those with smaller lesions sufficiently isolated from adjacent organs. Complications may be minimized when these approaches are applied selectively.

Adult↗
PubMed2000

Principles of sentinel lymph node identification: background and clinical implications.

The management of clinically negative regional lymph nodes in early-stage melanoma has been controversial for many years. While some advocate wide excision of the primary with elective node dissection (ELND), others recommend excision of the primary alone and therapeutic node dissection (TLND) for recurrences in the nodal basin. ELND is based on the concept that metastases occur by passage of the tumor from the primary to the regional nodes and distant sites, in which case early dissection of regional nodes will disrupt metastatic progression and prevent the spread of disease. Advocates of the "wait and watch" approach suggest that regional node metastases are markers for disease progression and that distant disease can occur without node metastases. Four randomized prospective studies comparing ELND and TLND have not demonstrated overall survival advantage for ELND, but suggest that patients with early regional metastases may benefit from ELND. As an alternative, Morton et al., from UCLA and the John Wayne Cancer Institute, devised intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL). These minimally invasive operative procedures allow identification of the first and key (sentinel) lymph node (SN). The technique accurately maps the lymphatics by lymphoscintigraphy, and vital blue dye leads the surgeon to the SN. The pathologist then concentrates on seeking metastases in the nodes most likely to contain metastases. Patients with tumor-positive SN undergo completion lymph node dissection (CLND), while those without SN metastases avoid the complications and costs associated with this procedure. Morton et al., in a report on their initial experience of LM/SL, performed CLND in all cases regardless of SN tumor status and demonstrated the precise staging capacity of the procedure. Since this initial report, numerous studies have validated the accuracy and low morbidity of the procedure. Each center must master a learning phase. The procedure is dependent on the close cooperation of nuclear medicine physicians, surgeons, and pathologists. While LM/SL is now almost standard practice in the US, the results of clinical trials are awaited to determine whether LM/SL can replace ELND and TLND in the management of early-stage melanoma.

Humans↗
PubMed2000

Alpha4 integrins in cardiovascular development and diseases.

Alpha4 integrins (alpha4beta1 and alpha4beta7) have a restricted distribution pattern and are critical for the development and diseases of the cardiovascular system. alpha4 integrins support unique biological properties such as promoting cell migration and inhibiting cell spreading and focal adhesion formation. We have found that the alpha4 integrin subunit directly and tightly binds to a signaling adapter molecule, paxillin, and disruption of the alpha4-paxillin interaction interferes with many of alpha4-dependent biological functions. Consequently, the interaction of alpha4 integrins with paxillin may play an important role in regulating alpha4-mediated functions. This review focuses on what we have known about the alpha4-paxillin interaction and discusses the possible mechanism of regulation for this interaction.

Animals↗
PubMed1999

Saliva as an alternate for blood to measure concentrations of acetone under exposure to isopropanol.

OBJECTIVES: In occupational medicine, blood concentrations are often measured to judge the internal burden of workers at work-place during exposure to a potentially hazardous substance. However, blood-withdrawals are invasive and can often not be taken at work-place due to hygienic reasons. Sampling of saliva is non-invasive and easy to perform even at workplace. In order to substitute blood analysis, analysis of saliva has to be as specific and sensitive as blood investigations. Therefore acetone-concentrations in blood and in saliva during exposure to isopropanol were compared. METHODS: 18 healthy non-smokers were exposed to 360 ppm isopropanol in an exposure chamber over 4 h. Once an hour during exposure and 30 min after, blood and saliva were sampled. Saliva was collected by a cotton plug over 10 minutes and stored in an airtight closed headspace tube. Concentrations of the metabolite acetone were measured by gas chromatography. - RESULTS: The concentrations of acetone in blood and saliva rose continually during exposure and dropped after exposure-cessation. High correlations between concentrations of acetone in blood and saliva were found for each individual and the entire group (entire group: r = 0.8568, p <0.0001, y = 0.8374x - 0.4404). CONCLUSIONS: Acetone-measurement in saliva is a non-invasive, easily conductable and reliable method for estimating the internal burden of isopropanol-exposure. Further studies for the standardization and validation are necessary to impose a threshold limit value on work-place isopropanol-exposure.

2-Propanol↗
PubMed1999

Binding of paxillin to alpha4 integrins modifies integrin-dependent biological responses.

The alpha4 integrins are indispensable for embryogenesis, haematopoiesis and immune responses, possibly because alpha4 regulates cellular functions differently from other integrins through its cytoplasmic tail. We used novel mimics of the alpha4 tail to identify molecules that could account for alpha4-specific signalling. Here we report that the alpha4 tail, but not several other alpha-subunit tails, binds tightly to the signalling adaptor paxillin. Paxillin physically associated with alpha4 integrins in Jurkat T cells at high stoichiometry, and joining the alpha4 tail to alphaIIb resulted in a complex of integrin alphaIIbbeta3 with paxillin. This association markedly enhanced the rates of alphaIIbbeta3-dependent phosphorylation of focal adhesion kinase and cell migration. It also reduced cell spreading, focal adhesion and stress fibre formation. A point mutation within the alpha4 tail that disrupts paxillin binding reversed all of these effects. Furthermore, alpha4beta1-dependent adhesion to VCAM-1 led to spreading of mouse embryonic fibroblasts derived from paxillin-null but not from wild-type mice. Thus, the tight association of paxillin with the alpha4 tail leads to distinct biochemical and biological responses to integrin-mediated cell adhesion.

Animals↗
PubMed1999

Evaluation of the role of mitogen-activated protein kinases in the expression of inducible nitric oxide synthase by IFN-gamma and TNF-alpha in mouse macrophages.

The expression of inducible nitric oxide synthase (iNOS) by macrophages is stimulated by coexposure to IFN-gamma and a number of stimuli, including TNF-alpha. Recent work has shown that TNF-alpha activates members of the mitogen-activated protein kinase family that subsequently trans-activate transcription factors implicated in the regulation of iNOS expression. The objective of this study was to systematically evaluate the role of: 1) p42mapk/erk2, 2) p46 c-Jun NH2-terminal kinase/stress-activated protein kinase (p46 JNK/SAPK), and 3) p38mapk in the induction of iNOS expression during costimulation of mouse macrophages with IFN-gamma and TNF-alpha. All three kinases were activated during costimulation with IFN-gamma and TNF-alpha. However, specific antagonism of the p42mapk/erk2 and p38mapk with PD98059 and SKF86002, respectively, had no effect on the induction of iNOS expression. In contrast, blockade of all three kinases with N-acetylcysteine completely blocked the induction of iNOS expression. In addition, specific antagonism of the JNK/SAPK upstream kinases MEKK (mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase) and MKK4 (mitogen-activated protein kinase kinase 4) with dominant inhibitory mutants blocked transcriptional activation of the iNOS promoter in response to costimulation with IFN-gamma and TNF-alpha. Collectively, these findings support the involvement of p46 JNK/SAPK and its upstream kinases in regulating the induction of iNOS following ligation of the TNF-alpha receptor CD120a (p55) in the presence of IFN-gamma.

3T3 Cells↗
PubMed1999

Transcatheter arterial chemoembolization as primary treatment for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) in Western populations has historically been associated with poor survival. METHODS: In this study, we conducted a 7-year retrospective analysis of patients with HCC undergoing transcatheter arterial chemoembolization (TACE) at our institution and examined demographics, outcomes, and complications. RESULTS: During the period of study, 39 patients (25 male [64%], mean age 58 [range 17 to 86]) underwent a total of 78 chemoembolization treatments. During the same time period, an additional 31 patients received supportive care only. The majority of patients had late stage disease (American Joint Committee on Cancer stage III, IVa, or IVb) with no statistical difference noted between the two groups (P = 0.2). However, patients receiving supportive care only had significantly worse hepatic dysfunction by Child's classification (P = 0.005). Twenty-nine patients (74%) had documented cirrhosis, with hepatitis C being the most common cause in 11 of 29 (38%). In patients undergoing TACE, overall actuarial survival was 35%, 20%, and 11% at 1, 2, and 3 years with a median survival of 9.2 months, significantly improved over the group receiving supportive care only (P < 0.0001). Median survival for the group receiving supportive care was less than 3 months. Neither age nor stage had a significant impact on survival. The most common complications of TACE included transient nausea, abdominal pain, vomiting, and fever. CONCLUSIONS: TACE is a safe and effective therapeutic option for selected patients with HCC not amenable to surgical intervention.

Abdominal Pain↗
PubMed1999

18Fluorodeoxyglucose-positron emission tomography in the management of patients with suspected pancreatic cancer.

OBJECTIVE: To assess the accuracy and clinical impact of 18fluorodeoxyglucose-positron emission tomography (18FDG-PET) on the management of patients with suspected primary or recurrent pancreatic adenocarcinoma, and to assess the utility of 18FDG-PET in grading tumor response to neoadjuvant chemoradiation. SUMMARY BACKGROUND DATA: The diagnosis, staging, and treatment of pancreatic cancer remain difficult. Small primary tumors and hepatic metastases are often not well visualized by computed tomographic scanning (CT), resulting in a high incidence of nontherapeutic celiotomy and the frequent need for "blind resection." In addition, the distinction between local recurrence and nonspecific postoperative changes after resection can be difficult to ascertain on standard anatomic imaging. 18FDG-PET is a new imaging technique that takes advantage of increased glucose metabolism by tumor cells and may improve the diagnostic accuracy of preoperative studies for pancreatic adenocarcinoma. METHODS: Eighty-one 18FDG-PET scans were obtained in 70 patients undergoing evaluation for suspected primary or recurrent pancreatic adenocarcinoma. Of this group, 65 underwent evaluation for suspected primary pancreatic cancer. Nine patients underwent 18FDG-PET imaging before and after neoadjuvant chemoradiation, and in eight patients 18FDG-PET scans were performed for possible recurrent adenocarcinoma after resection. The 18FDG-PET images were analyzed visually and semiquantitatively using the standard uptake ratio (SUR). The sensitivity and specificity of 18FDG-PET and CT were determined for evaluation of the preoperative diagnosis of primary pancreatic carcinoma, and the impact of 18FDG-PET on patient management was retrospectively assessed. RESULTS: Among the 65 patients evaluated for primary tumor, 52 had proven pancreatic adenocarcinoma and 13 had benign lesions. 18FDG-PET had a higher sensitivity and specificity than CT in correctly diagnosing pancreatic carcinoma (92% and 85% vs. 65% and 62%). Eighteen patients (28%) had indeterminate or unrecognized pancreatic masses on CT clarified with 18FDG-PET. Seven patients (11%) had indeterminate or unrecognized metastatic disease clarified with 18FDG-PET. Overall, 18FDG-PET suggested potential alterations in clinical management in 28/65 patients (43%) with suspected primary pancreatic adenocarcinoma. Of the nine patients undergoing 18FDG-PET imaging before and after neoadjuvant chemoradiation, four had evidence of tumor regression by PET, three showed stable disease, and two showed tumor progression. CT was unable to detect any response to neoadjuvant therapy in this group. Eight patients had 18FDG-PET scans to evaluate suspected recurrent disease after resection. Four were noted to have new regions of 18FDG-uptake in the resection bed; four had evidence of new hepatic metastases. All proved to have metastatic pancreatic adenocarcinoma. CONCLUSIONS: These data confirm that 18FDG-PET is useful in the evaluation of patients with suspected primary or recurrent pancreatic carcinoma. 18FDG-PET is more sensitive and specific than CT in the detection of small primary tumors and in the clarification of hepatic and distant metastases. 18FDG-PET was also of benefit in assessing response to neoadjuvant chemoradiation. Although 18FDG-PET cannot replace CT in defining local tumor resectability, the application of 18FDG-PET in addition to CT may alter clinical management in a significant fraction of patients with suspected pancreatic cancer.

Adenocarcinoma↗
PubMed1999

Radiofrequency ablation: a novel primary and adjunctive ablative technique for hepatic malignancies.

The majority of primary and metastatic tumors of the liver are not amenable to surgical resection at presentation. Radiofrequency ablation (RFA) is a new modality for local tumor destruction with minimal local and systemic complications. We prospectively reviewed the experience with RFA at a single institute as a primary or adjunctive ablative technique in the treatment of hepatic malignancies. Between November 1997 and December 1998, 30 patients with primary or metastatic hepatic lesions were treated with RFA at the John Wayne Cancer Institute and the Cancer Center at Century City Hospital. Pathology of the treated lesions included colorectal metastases (29 in 14 patients), neuroendocrine metastases (29 in 4 patients), noncolorectal metastases (29 in 9 patients), and hepatocellular carcinoma (6 in 3 patients). Twelve patients underwent RFA laparoscopically, 12 at celiotomy, and the remaining 6 patients had percutaneous ablation. RFA was the only procedure in 17 patients, whereas the remainder underwent a combination of RFA and other procedures including resection, cryosurgical ablation, and hepatic artery infusion pump placement. Median length of stay for all patients was 6 days (2 days for laparoscopic patients). A single complication of a delayed intrahepatic abscess was noted in this series (3%). There have been no deaths associated with RFA. At a median follow-up of 5 months, 16 patients remain disease free, and 10 are alive with disease. RFA is a safe and effective method of tumor ablation for hepatic malignancies. This technique can be performed laparoscopically, at celiotomy, or percutaneously and can be used as a primary technique or in conjunction with other interventional procedures.

Adenocarcinoma↗
PubMed1999

Optimal interpretation of FDG PET in the diagnosis, staging and management of pancreatic carcinoma.

UNLABELLED: This study had two purposes: to optimize the semiquantitative interpretation of 18F-fluorodeoxyglucose (FDG) PET scans in the diagnosis of pancreatic carcinoma by analyzing different cutoff levels for the standardized uptake value (SUV), with and without correction for serum glucose level (SUV(gluc)); and to evaluate the usefulness of FDG PET when used in addition to CT for the staging and management of patients with pancreatic cancer. METHODS: Sixty-five patients who presented with suspected pancreatic carcinoma underwent whole-body FDG PET in addition to CT imaging. The PET images were analyzed visually and semiquantitatively using the SUV and SUV(gluc). The final diagnosis was obtained by pathologic (n = 56) or clinical and radiologic follow-up (n = 9). The performance of CT and PET at different cutoff levels of SUV was determined, and the impact of FDG PET in addition to CT on patient management was reviewed retrospectively. RESULTS: Fifty-two patients had proven pancreatic carcinoma, whereas 13 had benign lesions, including chronic pancreatitis (n = 10), benign biliary stricture (n = 1), pancreatic complex cyst (n = 1) and no pancreatic pathology (n = 1). Areas under receiver operating characteristic curves were not significantly different for SUV and SUV(gluc). Using a cutoff level of 3.0 for the SUV, FDG PET had higher sensitivity and specificity than CT in correctly diagnosing pancreatic carcinoma (92% and 85% versus 65% and 61%). There were 2 false-positive PET (chronic pancreatitis, also false-positive with CT) and 4 false-negative PET (all with true-positive CT, abnormal but nondiagnostic) examinations. There were 5 false-positive CT (4 chronic pancreatitis and 1 pancreatic cyst) and 18 false-negative CT (all with true-positive FDG PET scans) examinations. FDG PET clarified indeterminate hepatic lesions or identified additional distant metastases (or both) in 7 patients compared with CT. Overall, FDG PET altered the management of 28 of 65 patients (43%). CONCLUSION: FDG PET is more accurate than CT in the detection of primary tumors and in the clarification and identification of hepatic and distant metastases. The optimal cutoff value of FDG uptake to differentiate benign from malignant pancreatic lesions was 2.0. Correction for serum glucose did not significantly improve the accuracy of FDG PET. Although FDG PET cannot replace CT in defining local tumor extension, the application of FDG PET in addition to CT alters the management in up to 43% of patients with suspected pancreatic cancer.

Adenocarcinoma↗
PubMed1999

[Time zone shift and the immune system during long-distance flights].

Recurrent infections could be seen in frequent flyers indicating an impaired immune reaction after long-distance flights. The increase of the concentration of neopterin points to an activation of the cellular part of the immune system. In combination with the altered differential blood counts, the changes in the proliferation rate of lymphocytes and the immune phenotyping the increase of neopterin leads to an explanation of the down-regulation of the immune system after flights. The mild hypoxia on board of an aircraft triggers an increase of catecholamines and cortisol in serum. Catecholamines lead to a shift of leukocytes from different compartments to the circulating blood and to an activation of immune cells. Cortisol triggers the differentiation of a subgroup of T-Lymphocytes with a rise in TH2-helper cells and a down-regulation of TH1-cells. The latter ones are, however, essential for an induction of a reaction of the cellular immune system and so the function of the cellular part of the immune system will be reduced. If no infection occurs, the concentration of neopterin in serum will drop to normal.

Aerospace Medicine↗
PubMed1999

[Time zone shifts and jet lag after long-distance flights].

Long distance flights with rapid time zone shifts of more than 3 hours lead to a dissociation of the inner circadian clock to the outer pacer. Additionally, the different endogenous circadian rhythms will not longer be synchronized by the endogenous pacer melatonin. This leads to complaints like sleepiness, sleep-disturbances and others. These symptoms are called jet-lag. The subject's performance is disturbed, as well. Different studies showed smaller problems with jet lag when travelling to the west. Since the inner circadian rhythm tends to be 24 up to 26 hours, travelling to the west with a prolongation of the daylight will be tolerated better than flights to the east with a shortening of the day length. Rapid time zone shifts with more than 8 hours to the east lead to individual different ways of resynchronization. Subject either try to adapt to the new time zone by shortening the day (backward adaptation) or they resynchronize forward with a longer duration of adaptation time. Elder subjects with already diminished circadian hormonal rhythm often get more problems concerning symptoms of the jet-lag and in time to recover from the disturbance of the inner clock. No differences can be found between business travelers, tourists and high-performance sportsmen. After flights to the west within 3 to 7 days, most of our inner circadian rhythm will be re-synchronized. After flights to the east, resynchronization can take 5 to 14 days. A symptomatic therapy of jet lag symptoms with a short-acting benzodiazepine like triazolam in a dosage of 12.5 mg or less is well tolerated. A therapy with oral melatonin in a dosage of 0.5 to 5 mg/day given in the evening 1 to 2 hours prior to the desired sleeping-time may be helpful for a group of subjects. Another group of subjects will not have any benefit of a therapy with melatonin, but cannot be defined in advance. A recommendation for a therapy with melatonin to treat jet lag symptoms cannot be given at the moment, since scientific data are still missing. Additionally, the same contaminants, which caused some deaths, as in the related substance tryptophan has been found in some tablets of melatonin.

Aircraft↗
PubMed1998

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Adult↗
PubMed1998

Management of bronchobiliary fistula as a late complication of hepatic resection.

Bronchobiliary fistula is an uncommon but remarkable complication after hepatic resection. The case reported illustrates the clinical presentation and preferred initial management of these fistulae. A 61-year-old white male underwent two wedge resections for colorectal metastases to the liver with removal of a portion of the right diaphragm. Four years later, he developed obstructive jaundice secondary to tumor recurrence in the porta hepatis, which required endoscopic stent placement, radiation, and chemotherapy. Almost 2 years later, he developed frank biliptysis. Percutaneous transhepatic cholangiography (PTC) revealed occlusion of the common hepatic duct stent and a bronchobiliary fistula. With adequate reestablishment of common duct drainage, the patient rapidly improved and was discharged free of symptoms. Bronchobiliary fistulae are rare complications of hepatic resection that can present from days to years after operation. Endoscopic retrograde cholangiopancreatography and PTC are the diagnostic studies of choice and offer the possibility of therapeutic intervention. Although large series in the literature emphasize the surgical management of bronchobiliary fistulae, the reoperative procedures tend to be complicated, with a significant morbidity and mortality. Nonsurgical interventions via endoscopic retrograde cholangiopancreatography or PTC are more recently notably successful when resolution of a distal biliary obstruction is accomplished. Only after aggressive attempts at nonoperative, interventional techniques have failed should operative approaches be entertained.

Bile Duct Diseases↗
PubMed1998

Hepatocellular carcinoma outcomes based on indicated treatment strategy.

Hepatocellular carcinoma (HCC) in Western populations historically has been associated with poor survival. In this study, we conducted a 7-year retrospective analysis of patients evaluated at our institution with HCC to determine the effects of newer treatment strategies on outcome. During the period of study, 117 patients [86 (74%) male; mean age, 59 years (range, 16-85)] were evaluated with treatment as follows: surgical resection in 22 (19%), chemoembolization with or without systemic chemotherapy in 40 (35%), systemic treatment alone in 16 (13%), orthotopic liver transplantation in 8 (7%), and supportive care only in 31 (26%). Sixty-nine patients (59%) had documented cirrhosis, with hepatitis C being the most common cause in 27 of 69 (39%). In patients receiving no treatment, median survival was just under 3 months, with only two 1-year survivors. Patients with orthotopic liver transplantation had 1-, 2-, and 3-year survival rates of 87, 87, and 58 per cent compared with 69, 52, and 43 per cent in surgically resected patients. Survival after chemoembolization was 35, 20, and 11 per cent at 1, 2, and 3 years, whereas survival after systemic chemotherapy was 30 and 15 per cent at 1 and 2 years, respectively. One-year survival was improved in noncirrhotic patients compared with cirrhotics (47% vs 29%; P < 0.05) but was no different in patients younger than 55 years compared with older patients (38% vs 38%). When possible, surgical treatment strategies offer superior survival.

Adolescent↗
PubMed1997

Interferon-gamma and transforming growth factor-beta modulate the activation of mitogen-activated protein kinases and tumor necrosis factor-alpha production induced by Fc gamma-receptor stimulation in murine macrophages.

Engagement of receptors for the Fc region of IgG (Fc gamma R) can activate a variety of biological responses in macrophages, and these responses can be modulated either positively or negatively by co-stimulation with a variety of agents including cytokines such as interferon-gamma (IFN-gamma) and transforming growth factor-beta (TGF-beta). We have previously demonstrated that Fc gamma R crosslinking activates the mitogen-activated protein kinase (MAPK) family members p42MAPK, p38, and JNK. Herein, we examined the modulatory effect of IFN-gamma, TGF-beta, and platelet-activating factor (PAF) on Fc gamma R-induced MAPK activation in murine macrophages. Fc gamma R-induced activation of p42MAPK and JNK was augmented nearly two-fold by pretreatment with IFN-gamma. Conversely, TGF-beta pretreatment suppressed Fc gamma R-induced activation of p42MAPK, JNK, and p38. These modulatory effects of IFN-gamma and TGF-beta on MAPK activation correlated with changes in Fc gamma R-stimulated TNF-alpha production by these two cytokines.

Animals↗
PubMed1997

Fc gamma receptor cross-linking activates p42, p38, and JNK/SAPK mitogen-activated protein kinases in murine macrophages: role for p42MAPK in Fc gamma receptor-stimulated TNF-alpha synthesis.

Fc gamma R cross-linking on murine macrophages resulted in the activation of mitogen-activated protein kinase (MAPK) family members p42MAPK, p38, and c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK). The temporal pattern of activation was distinct for each kinase. p42MAPK activation peaked at 5 min after receptor cross-linking, while peak p38 activity occurred 5 to 10 min later. Maximal JNK/SAPK activation occurred 20 min after Fc gamma R cross-linking. The selective MAPK/extracellular signal-regulated kinase-1 (MEK-1) inhibitor PD 098059 inhibited activation of p42MAPK induced by Fc gamma R cross-linking, but not p38 or JNK/SAPK activation. PD 098059 also inhibited the synthesis of TNF-alpha induced by Fc gamma R cross-linking (IC50 approximately 0.1 microM). Together, these results suggest that 1) the activation of MAPKs may play a role in Fc gammaR signal transduction, and 2) the activation of p42MAPK is necessary for Fc gamma R cross-linking-induced TNF-alpha synthesis.

Animals↗