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Biomedical subjects

C A Jacobi

Publications and source records attributed to C A Jacobi.

At least 55 records · Page 3Linked to original sources
PubMed2000

Triggering the ExoS regulon of Pseudomonas aeruginosa: A GFP-reporter analysis of exoenzyme (Exo) S, ExoT and ExoU synthesis.

The ExoS regulon of Pseudomonas aeruginosa encodes diverse type III secreted effector proteins which have been shown to exert cytotoxic effects in cell culture experiments. However, little information exists about the environmental conditions and stimuli for upregulation of the ExoS regulon. Translational reporter fusion proteins of exoenzyme (Exo) S, ExoT and ExoU, as well as the type II secreted exotoxin A (ETA) to the green fluorescent protein (GFP), were constructed in order to compare exoprotein production under diverse growth conditions. Reporter protein activity was recorded by FACS-analysis and by conventional and confocal laser scanning microscopy. Low ion concentration induced co-ordinated upregulation of ExoS, ExoT and ExoU with a maximum effect at 37 degrees C. A dose-dependent upregulation was seen with human serum or increasing NaCl concentrations. A type III secretion-negative pcrD mutant of P. aeruginosa showed a weak ExoS response to environmental stimuli, compared with the parental strain, suggesting a negative regulatory mechanism. Co-culture with the mammalian cell lines J774A.1 or HeLa led to rapid upregulation of ExoS, ExoT and ExoU synthesis. These data suggest that the ExoS regulon of P. aeruginosa can be triggered by a variety of environmental signals as well as by cell contact with eukaryotic cells.

ADP Ribose Transferases↗
PubMed2000

Cardiopulmonary changes during laparoscopy and vessel injury: comparison of CO2 and helium in an animal model.

BACKGROUND: Injury of venous vessels during elevated intraperitoneal pressure is thought to cause possible fatal gas embolism, and helium may be dangerous because of its low solubility. METHODS: Twenty pigs underwent laparoscopy with either CO2 (n=10) or helium (n=10) with a pressure of 15 mm Hg and standardized laceration (1 cm) of the vena cava inferior. After 30 s, the vena cava was clamped, closed endoscopically by a running suture and unclamped again. During the procedure changes of cardiac output (CO), heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary artery wedge pressure (PAWP), end tidal CO2 pressure (PETCO2), and arterial blood gas analyses (pH, pO2 and pCO2) were investigated. RESULTS: No animal died during the experimental course (mean blood loss during laceration: CO2, 157+/-50 ml; helium, 173+/-83 ml). MAP and CO values showed a decrease after laceration of the vena cava in both groups that had already been completely compensated for before suturing. PETCO2 increased significantly after CO2 insufflation (P<0.01), while helium showed no effect. Laceration of the vena cava caused no significant changes in PETCO2 values in either group. Significant acidosis and an increase of pCO2 were only found in the CO2 group. CONCLUSIONS: The incidence of gas embolism during laparoscopy and accidental vessel injury seems to be very low. With the exception of acidosis and an increase of PETCO2 in the CO2 group, there were no differences in cardiopulmonary function between insufflation of CO2 and helium.

Animals↗
PubMed2000

Influence of intraperitoneal and systemic application of taurolidine and taurolidine/heparin during laparoscopy on intraperitoneal and subcutaneous tumour growth in rats.

BACKGROUND: Recent clinical and experimental studies investigated the problem and possible pathomechanisms of portsite metastases after laparoscopic resection of malignant tumours. A generally accepted approach to prevent these tumour implantations does not exist so far. METHODS: After subcutaneous and intraperitoneal injection of 10(4) cells of colon adenocarcinoma (DHD/K12/TRb) the influences of either taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumour growth were investigated in 105 rats undergoing laparoscopy with carbon dioxide. The animals were then randomised into seven groups. A pneumoperitoneum was established using carbon dioxide for 30 min (8 mmHg). Three incisions were used: median for the insufflation needle, and a right and left approach in the lower abdomen for trocars. To investigate the intraperitoneal (local) influence of either taurolidine and heparin on tumour growth the substances were instilled intraperitoneally. Systemic effects were expected when the substances were applied intravenously (iv). Synergistic influences were tested when both application forms were combined. The number and the weight of tumours as well as the incidence of abdominal wall and port-site metastases were determined four weeks after intervention. Blood was taken to evaluate the influences of taurolidine and heparin on systemic immunologic reactions: seven days before laparoscopy. two hours, two days. seven days, and four weeks after operation, and the peripheral lymphocytes were determined. RESULTS: Intraperitoneal (ip) tumour weight in rats receiving taurolidine (median 7 mg) and taurolidine/heparin (0 mg) intraperitoneally was significantly reduced when compared to the control group (52 mg) (P = 0.001). There was no difference of subcutaneus tumour growth among the groups (P = 0.4). Trocar recurrences were decreased when taurolidine was applied ip (3115). ipiv (4/15), and ip in combination with heparin (4/15) in comparison to the control group (10/15). Immediately after intervention treated and untreated groups showed a peripheral lymphopenia. CONCLUSIONS: The intraperitoneal therapy with taurolidine and the combination with heparin inhibits the intraperitoneal tumour growth and trocar recurrences. Neither the intraperitoneal nor the systemic application or the combination of taurolidine and heparin did reduce the subcutaneous tumour growth. The intervention caused a lymphopenia which was compensated on day two.

Adenocarcinoma↗
PubMed2000

The impact of laparoscopic biopsy of pancreatic lymph nodes with helium and carbon dioxide on port site and liver metastasis in BOP-induced pancreatic cancer in hamster.

The influence of pancreatic biopsy during laparoscopy with carbon dioxide (CO2) and helium on the incidence of port site and liver metastasis in pancreatic carcinoma is still unknown. Ductal adenocarcinoma of the pancreas was induced in Syrian hamsters (n = 30) by injection of N-nitrosobis-2-oxopropylamin (BOP, 10 mg/kg body weight/week) for 12 weeks. In week 13, hamsters were randomized in 3 groups (n = 10): While in group 1 (gr. 1) a laparotomy and biopsy of pancreatic lymph nodes was performed, gr. 2 and gr. 3 underwent a laparoscopic biopsy either with CO2 or helium. Therefore, one trocar was located in the left (biopsy) and the right abdominal wall (camera). In the 18th week all animals were sacrificed and the incidence of abdominal wall, port site and liver metastases was histologically determined. While there were abdominal wall metastases after laparotomy in 10% (n = 1), we observed trocar metastases in the CO2 group in 20% (n = 2). However, there were no trocar metastases in the helium group. The incidence of liver metastasis did not differ between the laparotomy and the helium group (20% vs 30%), but was increased in the CO2 group (60%). Laparoscopic biopsy of pancreatic lymph nodes with CO2 increased the incidence of port site and liver metastases in pancreatic cancer. The helium group was equal to the laparotomy group in this respect. Thus, staging laparoscopy with helium might become an alternative to explorative laparotomy in pancreatic cancer.

Animals↗
PubMed2000

Does alpha-linolenic acid in combination with linoleic acid influence liver metastasis and hepatic lipid peroxidation in BOP-induced pancreatic cancer in Syrian hamsters?

Some fatty acids are reported to inhibit tumor growth of pancreatic carcinoma. However, it is still unknown if alpha-linolenic acid (ALA) and linoleic acid (LA) inhibit liver metastasis of ductal pancreatic adenocarcinoma. Therefore we studied the effect of these fatty acids on liver metastasis in the animal model of N-nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic adenocarcinoma in Syrian hamsters. Since lipid peroxidation seems to be involved in carcinogenesis and metastasis, we further analyzed the intrahepatic concentration of thiobarbituric acid-reactive substances (TBARS) and activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). We observed an increase in the incidence and the number of liver metastases in response to the combination of ALA and LA. This was accompanied by a decrease in hepatic GSH-Px activity and an increase in hepatic SOD activity and TBARS concentration. The increase in hepatic lipid peroxidation seems to be one possible mechanism of increasing liver metastasis in this study.

Adenocarcinoma↗
PubMed2000

Fundoplication: a model for immunologic aspects of laparoscopic and conventional surgery.

BACKGROUND AND PURPOSE: Immunologic investigations of laparoscopic and conventional procedures have recently been performed during cholecystectomy or colon resection, but the results might have been influenced by the amount of dissection or the presence of malignant tumor. Because fundoplication is characterized by moderate dissection and no resection, we supposed it to be an appropriate procedure for comparing immunologic changes during laparoscopic and conventional surgery. PATIENTS AND METHODS: Immunologic analysis (interleukin [IL]-6, IL-10, leukocytes, HLA-DR monocytes) was carried out on the peripheral blood of 34 patients who underwent elective Nissen fundoplication by the laparoscopic (LAP; N = 26) or conventional (OPEN; N = 8) technique for gastroesophageal reflux disease. Blood samples were obtained before and 1 and 4 hours after the beginning of the operation and on days 1, 2, 4, 7 after the procedure. RESULTS: A very fast and significant (P < 0.01) increase of the proinflammatory cytokines (IL-6, IL-10) and leukocytes and a decrease of cell-mediated functions (HLR-DR monocytes) were detected. Most of the analyzed measures had returned to preoperative values by 2 days after the procedure. All of the changes were similar in the two groups with the exception of IL-6. Throughout the post-operative study period, IL-6 concentrations were higher in the OPEN group, being significant 4 hours, 1 day, 2 days, and 4 days after the operation. CONCLUSION: The investigation measures do not give evidence that laparoscopic fundoplication is superior to conventional fundoplication in its immunologic effects.

Adult↗
PubMed2000

Yersinia enterocolitica invasin protein triggers IL-8 production in epithelial cells via activation of Rel p65-p65 homodimers.

Enteropathogenic Yersinia bacteria trigger the production of the proinflammatory chemokine IL-8, an important chemokine for the recruitment of polymorphonuclear leukocytes (PMN). Yersinia is resistant to phagocytosis by PMN, and the recruitment of these cells is thought to be part of a pathogenic strategy of Yersinia to establish infection by allowing the pathogen to gain access to, and disseminate within, host tissue. We report here that Yersinia expressing the outer membrane protein invasin triggers IL-8 production in epithelial cells. The 195 carboxyl-terminal amino acids of invasin when linked to latex beads are sufficient to trigger IL-8 production. By means of IL-8 promoter reporter gene assays and electrophoretic mobility shift assay experiments, the minimal optimal region of the IL-8 promoter responsive to invasin was identified and invasin-responsive control elements were characterized. Invasin-induced activation of the IL-8 promoter was found to be mediated through a previously identified NF-kappaB element. This NF-kappaB binding site preferentially binds Rel p65-p65 homodimers as well as some p50-p65 heterodimers in response to stimulation by invasin. Invasin-induced NF-kappaB activation correlated with degradation of IkappaBalpha and the inhibition of NF-kappaB by specific inhibitors of IkappaB activation blocked invasin-induced IL-8 secretion. Invasin-triggered IL-8 production does not depend on invasin-triggered uptake of bacteria, and is independent of a functional PI3-kinase. This report is the first to demonstrate the molecular basis of IL-8 production triggered by enteropathogenic bacteria. Together, these data elucidate the possible early pathomechanisms operating in Yersinia infection and may have implications for the design of novel therapeutics directed against this enteropathogen.

Adhesins, Bacterial↗
PubMed2000

Prognosis factors in carcinoma of the head of the pancreas.

BACKGROUND: Due to a low survival rate even after a R0 resection of cancer of the head of the pancreas, a strict indication for a pancreaticoduodenectomy seems to be sensible. We have therefore analyzed our patients for possible prognosis factors. METHODS: In a retrospective trial the courses of disease of all patients (1981-1996) with resected histologically proven carcinoma of the head of the pancreas were analyzed. The following patient-specific parameters were evaluated and examined in a single or multivariate analysis of prognosis factors: age, gender, tumor size (T status), lymph node involvement (N status), dimension of resection, operation method, time of operation, morbidity, clinic lethality and survival rate. RESULTS: Between 1981 and 1996, 500 patients with ductal adenocarcinoma of the head of the pancreas were treated surgically. The rate of resection increased from 32.1% (1981-1986) to 37.8% (1991-1996) whereas the mortality rate decreased from 13.3 to 7.3%. The 5-year survival rate after resection was 11.8% with a median survival time of 13.8 months. In a multivariate analysis, only small tumors (T1, p < 0.016), the R0 status (p < 0.017) and the resection had a significant influence on the survival rate. CONCLUSION: Prognosis factors in the treatment of pancreatic cancer were tumor size (T1), tumor resection and R0 status.

Adenocarcinoma↗
PubMed2000

Influence of octreotide and tamoxifen on tumor growth and liver metastasis in N-nitrosobis(2-oxopropyl)amine-induced pancreatic cancer in Syrian hamsters.

In prospective clinical trials single octreotide therapy or combined therapy with tamoxifen has improved the quality of life and survival time in patients with pancreatic cancer. In this study we analyzed the influence of octreotide and tamoxifen on tumor growth and liver metastases in chemically induced pancreatic adenocarcinoma in Syrian hamsters. Octreotide alone and the combined therapy (octreotide/tamoxifen) decreased the incidence of macroscopic pancreatic carcinomas as well as the number and size of liver metastases. The combined therapy showed no superior effect to octreotide alone. Furthermore, there was no difference between the tamoxifen and the control group.

Animals↗
PubMed1999

The cytotoxin YopT of Yersinia enterocolitica induces modification and cellular redistribution of the small GTP-binding protein RhoA.

Pathogenic Yersinia enterocolitica produces two virulence plasmid-encoded cytotoxins, YopE and YopT, that are translocated into target cells where they disrupt the actin cytoskeleton. Here we show that infection of cells with wild type Y. enterocolitica and a yopE mutant, but not with a yopT mutant, induces an increase in the electrophoretic mobility of the small GTPase RhoA. As tested by isoelectric focusing, YopT-dependent modification resulted in an acidic shift of RhoA. Furthermore, RhoA modification induced by YopT was accompanied by redistribution of membrane-bound RhoA toward the cytosol. Finally, a yopE mutant of Y. enterocolitica expressing the cytotoxic activity of YopT specifically disrupted RhoA-controlled actin stress fibers. These findings provide evidence for inactivation of RhoA by the translocated Y. enterocolitica cytotoxin YopT and suggest a novel inhibitory modification of RhoA by a bacterial virulence factor.

Animals↗
PubMed1999

[Gastrointestinal quality of life after duodenopancreatectomy in pancreatic carcinoma. Preliminary results of a prospective randomized study: pancreatoduodenectomy or pylorus-preserving pancreatoduodenectomy].

BACKGROUND: The Whipple operation (PD) is the standard operation in patients with cancer of the head of the pancreas and the periampullary region. However, the pylorus-preserving duodenopancreatectomy (PPPD) is supposed to be superior in gastrointestinal function. METHODS: In a prospective randomized trial (October 1994-October 1998) PD and PPPD were compared in terms of global and gastrointestinal quality of life, operation time, duration of hospital stay, transfusions and perioperative morbidity. Quality of life was analyzed under standardized conditions (EORTC-QLQ-30) pre- and postoperatively (weeks 2, 6, 12, 24, 36, 48, and 60). RESULTS: A duodenopancreatectomy was performed in 48 patients because of cancer of the head of the pancreas (n = 38) and the periampullary region (n = 10) (PD, n = 24; PPPD, n = 24). The PD and PPPD groups did not differ according to age, gender or UICC stage. Operation time was shorter in the PPPD group (206 +/- 48 vs 306 +/- 54 min) (P < 0.05). Morbidity did not differ between the two groups (PPPD 20% vs PD 30%, P > 0.05). While there was no difference in global quality of life, gastrointestinal quality of life was postoperatively increased in the PPPD group regarding appetite, nausea and diarrhea (P < 0.05). While the preoperative body weight was reached after 6 months in 85% of the PPPD group (n = 20), this was true in only 60% of the PD-group (n = 14) (P < 0.05). CONCLUSION: PPPD seems to be associated with a better postoperative gastrointestinal quality of life than PD.

Adult↗
PubMed1999

[Hormone therapy of postoperative recurrent pancreatic carcinoma with octreotide and tamoxifen].

BACKGROUND: In a prospective trial (October 1996-April 1998) the effect of octreotide and tamoxifen on the recurrence of pancreatic carcinoma after R0 resection was evaluated. METHODS: Patients with a local recurrence after curative resection of ductal adenocarcinoma of the pancreas were treated with 100 micrograms of octreotide three times a day and tamoxifen 20 mg once daily. The median survival time, quality of life (EO-RTC-QLQ-30) and side effects of the octreotide-tamoxifen group were compared with a historic cohort (n = 14) of patients treated in our department (9/95-9/96) according to the "best supportive care" concept. RESULTS: Recurrences were diagnosed after R0 resection in a mean time of 13 +/- 6.8 months. Patients treated with octreotide and tamoxifen had a significantly (P < 0.05) longer median survival time (7 months; range: 3-12) vs 3.5 months; range: 1.5-5). The octreotide-tamoxifen group suffered less from lack of appetite, nausea, fatigue, and pain and needed fewer analgesics. The only side effect of the octreotide-tamoxifen therapy was moderate diarrhea in 2 patients at the beginning of the therapy. CONCLUSION: Since combined therapy with octreotide and tamoxifen can be administered comfortably for outpatient treatment, this seems to represent progress in the palliative therapy of pancreatic cancer.

Aged↗
PubMed1999

[Rupture of the distal biceps tendon. Case report--modified after-care].

The surgical therapy of the rupture of a distal biceps tendon and a modified postoperative treatment is described. Mainpoint is the early treatment in anaclisis of Kleinert as it is standardized in the treatment of ruptures of the flexor tendons of the hand. A forearm orthesis with a simply ROM-joint without reboundmechanism was used. Possible benefits are shown and further industrial evolution seems to be indicated.

Braces↗
PubMed1999

Endoscopic surgery: fit for malignancy?

Neither experimental nor clinical data confirm the repeatedly published opinion that video-endoscopic surgery promotes tumor growth or the occurrence of implantation metastases in cancer patients. On the contrary, alterations due to pneumoperitoneum by the application of different gases, pressures, and temperatures might provide the basis for a new therapeutic approach to cancer surgery. Oncologically adequate resections defined by such terms as "no touch isolation" and "monobloc resection" can be performed video-endoscopically in a variety of intraabdominally or intrathoracically located cancers if a standardized technique is used. The benefit of video-endoscopic surgery is limited in large tumors, especially if they have reached the organ surface. There is still a major deficit in the clinical evaluation of video-endoscopic interventions in most oncologic diseases. Randomized studies comparing video-endoscopic and conventional surgery have been reported only for the resection of colorectal carcinoma. They show that laparoscopic resections can be performed with a minimum of postoperative complications to the same extent as conventional resections and offer several advantages during the early postoperative period. No reliable data from comparative trials are as yet available on the long-term results.

Endoscopy↗
PubMed1999

Is mesh fixation necessary in abdominal hernia repair? Results of an experimental study in the rat.

BACKGROUND: Abdominal hernia repair with implantation of synthetic meshes using the sublay technique has resulted in low recurrence rates and high patient satisfaction. AIM: The purpose of this experimental animal study was to investigate whether mesh fixation is necessary in abdominal hernia repair using a polypropylene mesh in the sublay technique. METHODS: Forty-five rats were divided into three groups after creating an abdominal wall defect (CG control group, no mesh implantation; NoFixG mesh implantation without fixation group; SG mesh with suture fixation group) with 15 animals in each group. End-points were clinical herniation pressure, hydroxyproline (HP) concentration, mesh shape and number of fibroblasts/collagen fibres of the anchor zone 7, 14 and 90 days after implantation. RESULTS: Herniation pressure, HP content and number of fibroblasts were similar between NoFixG and SG, although significantly higher in these groups than in the CG (P<0.05). Both mesh groups had significantly higher counts of fibroblasts and collagen fibres than the CG. Mesh shrinking occurred in both groups but was less in the SG. CONCLUSION: Mesh fixation was not mandatory in abdominal hernia repair using this animal model.

Animals↗
PubMed1999

K-ras mutations in tissue and stool samples from patients with pancreatic cancer and chronic pancreatitis.

BACKGROUND AND AIM: K-ras oncogene is the most promising molecular marker of pancreatic cancer. However, the incidence of single and combined K-ras mutations in stool and pancreatic tissue is unknown, and it is not clear whether detection of the K-ras oncogene in stool could be employed in screening tests. PATIENTS/METHODS: Stool and pancreatic tissue of patients with ductal adenocarcinoma (n = 36), cystadenocarcinoma (n = 1), periampullary carcinoma (n = 7), endocrine tumour (n = 2) and chronic pancreatitis (CP, n = 5) were analysed for mutated K-ras sequences prospectively. DNA of stool and pancreatic tissue was amplified by polymerase chain reaction and K-ras status was analysed by hybridisation. RESULTS: K-ras mutations were detected in the pancreatic tissue of 28 patients with ductal adenocarcinoma (78%), in 1 patient with cystadenocarcinoma, in 1 patient with periampullary carcinoma (14%) and in 1 patient with CP (20%). In 1 patient with an endocrine tumour, no K-ras mutations were diagnosed. K-ras mutations were detected in stool in 7 patients with ductal adenocarcinoma (20%), in 1 patient with cystadenocarcinoma and in 2 patients with CP (40%). Sensitivity of K-ras mutations for pancreatic cancer was 78% in tissue and 20% in stool. CONCLUSION: K-ras mutations lack specificity to discriminate malignant pancreatic disease from chronic inflammation in tissue and stool.

Adenocarcinoma↗
PubMed1999

Tumor size and lymph-node status in pancreatic carcinoma - is there a correlation to the preoperative immune function?

BACKGROUND AND AIMS: It has not been clarified whether there is a correlation between the tumor size and the preoperative immune function in pancreatic carcinoma. PATIENTS/METHODS: In a prospective trial, the influence of tumor size and lymph-node status on different immune system factors [interleukins (IL)-6 and -10, tumor necrosis factor (TNF)-alpha, CD3-, CD4-, and CD8-lymphocytes, and human leukocyte antigen (HLA)-DR-monocytes] was analyzed in 28 patients with pancreatic carcinoma and compared with a control group (n=20). There were 3 pancreatic carcinomas of the T1-tumor type, 20 T2- and 5 T3-tumors; 14 patients were in stage N1. RESULTS: In comparison with the control group, tumor patients preoperatively showed a significant increase of leukocytes (P=0.02), monocytes (P=0. 04), and granulocytes (P=0.03). The total count of lymphocytes, the number of CD3-, CD4- and CD8-lymphocytes, and the expression of HLA-DR on monocytes were significantly decreased as a sign of immunosuppression in tumor patients. A multivariate analysis proved that only tumor size (T-stage) but not lymph-node status correlates with the deficiency of immune competence. Progressive tumor size correlated with decreasing expression of HLA-DR on monocytes, CD3- (P=0.04) and CD8- (P=0.02) lymphocytes. In contrast IL-6, IL-10 (P=0. 04) and TNF-alpha (P=0.02) increased with progressive tumor size. CONCLUSION: Regarding the negative prognosis after resection, the preoperative immune status could be an additional help for decision between a resection or a preoperative immune stimulation in pancreatic carcinoma.

Case-Control Studies↗