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Biomedical subjects

M Menges

Publications and source records attributed to M Menges.

32 records · Page 2Linked to original sources
PubMed2000

Higher concentration of matrix-metalloproteinase 1 (interstitial collagenase) in H. pylori-compared to NSAID-induced gastric ulcers.

BACKGROUND/OBJECTIVE: Matrix metalloproteinases (MMPs) are implicated in the tissue destruction associated with inflammatory diseases. We postulated a causal involvement of MMP-1 in ulcerogenesis and quantified therefore the MMP-1 concentrations in biopsies of human gastric ulcers and the surrounding mucosa. Further, we correlated them with the individual ulcer etiology. METHODS: During upper endoscopy biopsy specimens of the ulcer and surrounding normal mucosa were taken from 45 patients with gastric ulcers of different etiology (Helicobacter pylori, NSAID-intake, both or none of these). MMP-1 concentration was measured using a MMP-1 ELISA in 35 patients, western blot was performed in the remaining 10 patients. RESULTS: In general, median expression of MMP-1 in the ulcer tissue was significantly increased compared to the surrounding mucosa (16.8 [4.7-33.4] vs. 10.9 [2.8-17.8] ng/mg protein) (p < 0.001). Western blot analysis revealed increased concentration of the active forms of MMP-1 in ulcer tissue. Interestingly, the MMP-1 concentration was significantly higher in 15 H.p.-induced ulcers compared to 19 NSAID-induced ones: 19.3 (8.3-33.2) vs. 11.4 (4.7-33.4) ng/mg protein, p = 0.0354). CONCLUSION: MMP-1-expression in the ulcer tissue depends on the ulcer etiology. However, MMP-1 does not seem to be causally involved in ulcerogenesis. In NSAID-induced ulcers the MMP-1-synthesis may be suppressed by NSAID-induced decrease of mucosal prostaglandin concentration.

Adult↗
PubMed2000

The double duct sign in patients with malignant and benign pancreatic lesions.

BACKGROUND: The double duct sign, a simultaneous stenosis of the common bile duct and the pancreatic duct by endoscopic retrograde cholangiopancreatography (ERCP), has been reported to predict the presence of pancreatic cancer with a high degree of certainty. METHODS: To test the specificity of the double duct sign for pancreatic cancer in patients with malignant and benign pancreatic lesions, we have reviewed all ERCP films obtained during a 24-month period (n = 1209) and corresponding clinical follow-up data obtained during a period of 4 years. RESULTS: Forty-three patients were identified as having a double duct stenosis on ERCP, 15% of whom did not have pancreatic carcinoma. In 4 patients chronic pancreatitis was confirmed by serial histologic sections of the surgical specimen. Data on the lengths of the stenotic segment in either the pancreatic duct or the bile duct did not contribute to a better discrimination between benign and malignant disease. CONCLUSION: The specificity of the double duct sign in predicting the presence of pancreatic cancer appears to be lower than previously reported. Better discrimination between malignant and benign disease of the pancreas will be difficult to achieve with existing imaging techniques.

Aged↗
PubMed2000

Sugar control of the plant cell cycle: differential regulation of Arabidopsis D-type cyclin gene expression.

In most plants, sucrose is the major transported carbon source. Carbon source availability in the form of sucrose is likely to be a major determinant of cell division, and mechanisms must exist for sensing sugar levels and mediating appropriate control of the cell cycle. We show that sugar availability plays a major role during the G(1) phase by controlling the expression of CycD cyclins in Arabidopsis. CycD2 mRNA levels increase within 30 min of the addition of sucrose; CycD3 is induced after 4 h. This corresponds to induction of CycD2 expression early in G(1) and CycD3 expression in late G(1) near the S-phase boundary. CycD2 and CycD3 induction is independent both of progression to a specific point in the cell cycle and of protein synthesis. Protein kinase activity of CycD2- and CycD3-containing cyclin-dependent kinases is consistent with the observed regulation of their mRNA levels. CycD2 and CycD3 therefore act as direct mediators of the presence of sugar in cell cycle commitment. CycD3, but not CycD2, expression responds to hormones, for which we show that the presence of sugars is required. Finally, protein phosphatases are shown to be involved in regulating CycD2 and CycD3 induction. We propose that control of CycD2 and CycD3 by sucrose forms part of cell cycle control in response to cellular carbohydrate status.

Arabidopsis↗
PubMed1999

Selection of a human anti-progesterone antibody fragment from a transgenic mouse library by ARM ribosome display.

In antibody-ribosome-mRNA complex (ARM) ribosome display, stable complexes of nascent protein, mRNA and ribosomes are produced in a eukaryotic in vitro expression system, through coupled transcription and translation of DNA lacking a 3' stop codon. Selection of the protein simultaneously captures the relevant mRNA, which is recovered as DNA by coupled reverse transcription-polymerase chain reaction (RT-PCR) performed on the intact complexes. Here, we describe the use of ARM display to select a specific human antibody fragment from a transgenic mouse library. The mice carry unrearranged gene segments of the human heavy (H) and kappa light (L) chain loci, while the endogenous murine H and kappa loci are functionally silenced; they respond to immunisation by production of fully human IgM antibodies. A library encoding human single-chain (sc) antibody (V(H)/K) fragments, in which V(H) domains and kappa light chains were combined at random by PCR, was prepared from spleen cells of transgenic mice immunised with progesterone-bovine serum albumin (BSA). Library diversity was demonstrated by sequencing. Progesterone-binding fragments were selected over five cycles of ARM display and the selected DNA cloned and expressed in Escherichia coli. Soluble V(H)/K fragments obtained in periplasmic extracts had the same specificity as ribosome-bound V(H)/K, supporting the view that folding and specificity of the displayed and soluble proteins are equivalent. The affinity of the expressed V(H)/K was approximately 10(-8) M. Sequencing showed that ARM display selected a single V(H)/V(L) combination (V(H)1-2, Vkappa4-1) and rearrangement, with a few mutational differences between clones. Monoclonal antibodies against progesterone-BSA obtained from hybridomas were encoded by the same V(H) and V(L) segments and had similar properties to the fragments obtained in vitro. The combination of ribosome display and transgenic mouse technologies is a rapid means of generating fully human antibody fragments in vitro for expression and further manipulation.

Amino Acid Sequence↗
PubMed1999

Kaposi's sarcoma of the pancreas mimicking pancreatic cancer in an HIV-infected patient. Clinical diagnosis by detection of HHV 8 in bile and complete remission following antiviral and cytostatic therapy with paclitaxel.

BACKGROUND: Diagnosis of pancreatic cancer is usually made by endoscopic retrograde cholangiopancreatography (ERCP) and corresponding findings in computed tomography (CT) or magnetic resonance imaging. Kaposi's sarcoma, a frequent tumor in individuals with a late-stage HIV infection, can be located in the gastrointestinal tract and cause identical symptoms to carcinoma of the same site. A close correlation of this tumor to human herpes virus 8 (HHV 8) has been known for several years and there are reports of successful antiproliferative therapy. METHODS: Aspirated pancreatic juice and bile was investigated for the presence of HHV 8 by polymerase chain reaction. The clinical course of the patient under antiviral therapy and treatment with paclitaxel was studied. RESULTS: A 47-yr-old HIV-infected man with a history of Kaposi's sarcoma of skin and lungs caused by obstructive jaundice in the years before was admitted. ERCP showed a typical double-duct sign and CT revealed a tumorous infiltration of the pancreatic head, highly suspicious for pancreatic adenocarcinoma. A mutation of the ki-ras gene could be ruled out and molecular analysis of bile identified HHV 8 by PCR. Intensive antiviral therapy, including foscarnet and treatment with paclitaxel led to a complete remission within 8 m.o. CONCLUSION: Kaposi's sarcoma of the pancreas possibly mimics pancreatic cancer in HIV-infected subjects. Diagnosis may be made by identification of HHV 8 in pancreatic juice or bile, and successful clinical outcome is possible by intensive antiviral and cytostatic treatment with paclitaxel.

Antineoplastic Agents, Phytogenic↗
PubMed1999

[Implantation metastasis at the exit site after percutaneous endoscopic gastrostomy in esophageal carcinoma].

In patients with esophageal cancer causing obstruction percutaneous endoscopic gastrostomy (PEG) is a well-established procedure with a low complication rate to provide sufficient enteral nutrition. We report on a 68-year-old patient suffering from inoperable squamous cell cancer of the proximal esophagus, who underwent PEG insertion prior to a combined radiochemotherapy. Initially bougienage was performed because of subtotal esophageal stenosis. Four months later a metastasis was found at the PEG exit site with involvement of the gastric wall, most likely caused by spread of tumor cells during insertion of the PEG.

Aged↗
PubMed1997

[Effect of physical activity on incidence of sudden cardiac death. Study of the Berlin-Reinickendorf and Berlin-Spandau population].

AIM: Our investigation examined the influence of regular physical activity and sudden extrenious situations on the incidence of sudden cardiac death (scd) in two different Berlin districts with a total population of 219,251 in the examined age-groups. PATIENTS AND METHOD: All cases of scd which occurred outside of the hospital and were documented as been induced from ventricular fibrillation were examined over a time period of 18 months. For each case the amount of and the intensity of their regular physical activity was determined. In addition the stress of the sudden extrenious situations was survived. The study population was divided into various groups depending upon their level of regular physical activity. For each group the incidence of sudden cardiac death was determined. Then the relative risk for scd during strenuous activity compared to inactivity was determined for each group. The influence of preexisting disease was calculated. RESULTS: 77 patients with scd induced from ventricular fibrillation were included in our study. In the sedentary group we found an incidence of 4.69 scd per 10(5) person-years, in the group with a low level of regular physical activity we found an incidence of 4.25, in the group with a middle level of regular physical activity an incidence of 2.63 and in the most active group 0.92 scd per 10(5) person-years. We found the relative risk for scd during highly strenuous activity compared with inactivity to be 150 in the sedentary group as opposed to 4.0 in the most active group. The preexisting illness status of the case-groups had no influence on the outcome. CONCLUSIONS: The results show that the risk of scd for all persons regardless of their levels of regular physical activity and their preillness status is higher during strenuous activity than during inactivity. The increase of the risk for scd during activity is the highest for persons with sedentary lifestyles, whereas the risk increase for persons with active lifestyles is minimal. The protective effect of regular physical activity for scd by far exceeds the risk increase of the actual strenuous situation.

Adult↗
PubMed1996

[Secondary amyloidosis in ulcerative colitis--successful treatment with colchicine].

A 20 year old male patient with a four-years-history of moderately active ulcerative colitis was admitted due to extensive generalized edema. He suffered from a nephrotic syndrome, which was caused by secondary renal amyloidosis due to the colitis. Under continuous low dose therapy with colchicine in addition to the usual colitis therapy proteinuria decreased from values above 10 g/die to about 3 g/die and edema disappeared completely. Secondary amyloidosis following inflammatory bowel disease is a rare event, in case of ulcerative colitis a true curiosity. Cases published so far are discussed.

Adult↗
PubMed1995

1 x ED90 dose of rocuronium bromide: tracheal intubation conditions and time-course of action.

The intubation conditions and time-course of action of a 0.3 mg kg-1 bolus of rocuronium were studied under alfentanil/propofol and fentanyl/thiopentone/enflurane anaesthesia. Forty healthy patients were randomly allocated to induction of anaesthesia with either alfentanil 20 micrograms kg-1 and propofol 2.0-2.5 mg kg-1, or fentanyl 3 micrograms kg-1 and thiopentone 4-6 mg kg-1. Approximately 5 min later, after calibration of mechanomyography, an i.v. bolus of 0.3 mg kg-1 rocuronium was administered. Laryngoscopy and tracheal intubation were attempted when maximum block occurred. Intubation was completed successfully in 39 patients. The passage of the tube was rated good or excellent in 18/20 (alfentanil/propofol group) and 18/19 patients in the other group. The times of onset were 65 s and 69 s, respectively. It is concluded that a 1 x ED90 dose of rocuronium will rapidly provide good or excellent intubation conditions in the majority of cases.

Adolescent↗
PubMed1994

[Diagnostic and intensive care problems in hemolytic uremic syndrome].

We observed a young man with apparently septic appendicitis who finally could be diagnosed as suffering from haemolytic uraemic syndrome (HUS) when spuriously normalising platelet counts were identified as a cell counter artifact. This case stresses the fact that automatically counted abnormal thrombocyte numbers should be examined by microscopy. Therapy is empirically based on corticosteroids, plasmapheresis and fresh frozen plasma. The application of thrombocyte concentrates should be avoided because of the risk of aggravating the disease process.

Adult↗
PubMedDate not supplied

Activation of resting T cells against the CA 72-4 tumor antigen with an anti-CD3/CA 72-4 bispecific antibody in combination with a costimulatory anti-CD28 antibody.

The poor prognosis of advanced gastric carcinoma requires new therapeutic approaches. Among these, the specific activation of resting lymphocytes by bispecific antibodies may be promising. Here we describe the generation and function of a bispecific monoclonal antibody (bi-mab) with specificity for CD3 and for the tumor antigen CA72-4 (TAG72) on various gastrointestinal tumors. We established a hybrid/hybridoma by somatic fusion of two hybridoma lines secreting antibodies against CA72-4 and CD3 respectively and characterized its bimab OKT3/B72.3. In combination with costimulatory anti-CD28 antibodies resting peripheral lymphocytes could be activated specifically by bi-mab OKT3/B72.3 with T cell proliferation and IL-2 secretion. The bi-mab OKT3/B72.3 could also trigger the cytotoxicity of these T cells toward, CA72-4+ cells in vitro. Our results indicate, that bi-mab OKT3/B72.3 in combination with an anti-CD28 mab can redirect T cell cytotoxicity specifically against CA72-4+ tumor cells implicating a novel strategy for the specific immunotherapy of CA72-4+ tumors.

Animals↗