Search PubMed⌕ Search

Biomedical subjects

M Lorenz

Publications and source records attributed to M Lorenz.

At least 19 recordsLinked to original sources
PubMed1996

Induction of glutathione-S-transferase-pi by short-chain fatty acids in the intestinal cell line Caco-2.

Glutathione S-transferases (GSTs) are a multigene family of detoxification and metabolizing enzymes that have been linked with the susceptibility of tissues to environmental carcinogens. In addition to their role as the main energy source in the colonic mucosa, short-chain fatty acids (SCFAs) have been found to act as potent antiproliferative and differentiating agents in various cancer cell lines. The objective of this study was to evaluate the effects of SCFAs on the induction of GSTpi in the intestine as a possible new anticarcinogenic mechanism of SCFAs. Studies were performed in Caco-2 cells, a cell line resembling functionally normal enterocytes. Cells, cultured in DMEM supplemented with 10% fetal calf serum, were studied from day 0 dpc (days post confluence) until 21 dpc and culture. SCFAs (acetate, propionate, butyrate) were added to give a final concentration of 5 mmol L(-1). At 0, 3, 6, 9, 15, and 21 dpc, protein, lactate dehydrogenase (LDH), alkaline phosphatase (AP) and GSTpi were measured. Butyrate supplementation significantly (P < or = 0.01) increased GSTpi levels compared with controls in a concentration-dependent manner. The effect was detectable within 3 dpc with a maximum at 15 dpc. In contrast to butyrate, the other SCFAs tested had no (acetate) or little effect (propionate). In conclusion, the data suggest that the anticancer effect of butyrate in part may be based on the induction of GSTpi activity, resulting in an enhanced detoxification capacity of the gut.

Butyrates↗
PubMed1996

Subarachnoid hemorrhage of unknown etiology.

During a 10-year-period, 80 of 510 (16%) patients with primary subarachnoid hemorrhage (SAH) had negative angiographic studies. On admission, 70 of 80 patients (88%) were in grades I-II according to Hunt and Hess, 9 (11%) in grade III, and 1 (1%) in grade IV. The most frequent CT feature was preponderance of subarachnoid blood in the peripontine cistern as observed in 35 of 51 cases (69%) in whom blood was visible on CT. During hospitalization, 3 patients (4%) rebled, and 3 others (4%) had an infarction. However, in all of these complicated cases maximum hemorrhage was outside the peripontine cistern. Outcome after hospitalization as assessed by the Glasgow-Outcome-Scale (GOS) was favorable (GOS 1 and 2) in all patients who had maximum blood in the peripontine cistern, but only in 62% showing preponderance of blood outside the peripontine cistern, and 4 of them (25%) had died (GOS 5). These differences are statistically significant (p < 0.001). Long-term outcome of 56 patients as graded according to the Activities of Daily Living (ADL) system was favorable in 88% of cases with peripontine hemorrhage who returned to normal activities (ADL 1). At the same time, another patient with diffuse hemorrhage had died. Thus, overall mortality was 8.9% at a mean observation time of 5.5 years. In conclusion, SAH of unknown etiology generally has a good prognosis, although a nonneglegible percentage of patients have persistent minor side-effects. In our experience, maximum blood in the peripontine cistern particularly indicates a favorable outcome, since all patients with this CT pattern survived in a good condition.

Adult↗
PubMed1995

Instability of the lumbar burst fracture and limitations of transpedicular instrumentation.

STUDY DESIGN: This study analyzed the changes in the load-displacement behavior of lumbar spine segments caused by burst fractures that were experimentally produced in fresh human cadaveric spines. The effect of three transpedicular surgical constructs on stability was investigated in each specimen. OBJECTIVES: To quantify the loss of mechanical stiffness caused by the injury, and to evaluate the stiffness of three transpedicular surgical constructs. SUMMARY OF BACKGROUND DATA: Although various investigators have studied the biomechanical characteristics of the burst fracture and surgical stabilization techniques, few have reported quantitative data on the three-dimensional biomechanical instability of these fractures. METHODS: Load-displacement data were acquired in flexion, lateral bending, and axial rotation for intact specimens, after the L1 burst fracture was created and after the T12-L2 segments were stabilized using Luque plates, VSP plates, and Isola rods with one transverse connector. RESULTS: Spines with burst fractures showed a bilinear load-displacement behavior with significant instability (loss of stiffness relative to intact) at low loads (up to 3 N.m) in flexion, lateral bending, and axial rotation. The loss of stiffness was greatest in axial rotation over the entire load range (up to 10 N.m). If posterior element injury also was present, a significantly larger loss of stiffness was observed in flexion and axial rotation. The three transpedicular constructs improved the stability of the injured spine beyond that of the intact spine in flexion and lateral bending at low loads. At high loads, they restored the stiffness to intact levels. However, in axial rotation they did not restore the stiffness to pre-injury level, particularly when the posterior column was disrupted. CONCLUSIONS: Reduction of the burst fracture returns the spine to its position of greatest inherent instability, essentially requiring the transpedicular instrumentation to be load bearing. To enhance mechanical stability, it may be necessary to augment the transpedicular construct, particularly when the posterior column is disrupted.

Aged↗
PubMed1995

The stimulatory effects of interleukin (IL)-12 on hematopoiesis are antagonized by IL-12-induced interferon gamma in vivo.

Interleukin (IL)-12 synergizes with other cytokines to stimulate the proliferation and differentiation of early hematopoietic progenitors in vitro. However, in vivo administration of IL-12 decreases peripheral blood counts and bone marrow hematopoiesis. Here, we used interferon (IFN) gamma receptor-deficient (IFN gamma R-/-) mice to investigate whether the in vivo inhibition of hematopoiesis by IL-12 is indirectly mediated by IL-12-induced IFN-gamma. IL-12 administered for 4 d (1 microgram/mouse per day) resulted in lower peripheral blood counts and a 2-fold decrease in bone marrow cellularity in wild-type mice, but not in IFN gamma R-/- mice. Bone marrow hematopoietic progenitors were decreased after IL-12 treatment in wild-type mice, but rather increased in IFN gamma R-/- mice. Splenic cellularity was 2.3-fold higher after IL-12 administration in wild-type mice, largely due to natural killer (NK) cell and macrophage infiltration together with some extramedullary hematopoiesis. In IFN gamma R-/- mice, spleen cellularity was less increased, there were fewer infiltrating NK cells, but a strong extramedullary hematopoiesis. Thus, alterations mediated by IL-12-induced IFN-gamma include reduction in bone marrow cellularity and hematopoietic progenitors, as well as pronounced splenomegaly, largely caused by NK cell infiltration. In the absence of IFN-gamma signaling, IL-12 promotes hematopoiesis, consistent with its in vitro activities.

Animals↗
PubMed1995

Switch transcripts in immunoglobulin class switching.

B cells can exchange gene segments for the constant region of the immunoglobulin heavy chain, altering the class and effector function of the antibodies that they produce. Class switching is directed to distinct classes by cytokines, which induce transcription of the targeted DNA sequences. These transcripts are processed, resulting in spliced "switch" transcripts. Switch recombination can be directed to immunoglobulin G1 (IgG) by the heterologous human metallothionein IIA promoter in mutant mice. Induction of the structurally conserved, spliced switch transcripts is sufficient to target switch recombination to IgG1, whereas transcription alone is not.

Animals↗
PubMed1995

An atomic model of the unregulated thin filament obtained by X-ray fiber diffraction on oriented actin-tropomyosin gels.

We present a model of the actin-tropomyosin complex in which the radial and azimuthal position of tropomyosin was adjusted to fit the X-ray fiber diffraction patterns from oriented actin-tropomyosin gels at a resolution of 1/8 A-1. We used the recently published atomic F-actin model for the calculations. The atomic model of tropomyosin was obtained by model-building a coiled coiled-coil structure from the tropomyosin sequence. The resulting atomic model is strongly preferred and shows strong electrostatic interactions between charged side-chains of tropomyosin residues and actin residues in subdomain 3 and subdomain 4. Furthermore, calculations of enthalpies based upon electrostatic interactions indicate that there is a favored rotational position of the tropomyosin core at the calculated azimuthal and radial position given by the X-ray refinement. Rotations of the tropomyosin strand out of this position turn strongly attractive electrostatic interactions into repulsive forces. The resulting binding radius of 39 A and the determined azimuthal position of tropomyosin are in good agreement with electron microscopy reconstructions and neutron diffraction experiments. Furthermore, the calculated position of tropomyosin would still partly block the rigor interaction of myosin cross-bridges with actin, whereas it very likely allows undisturbed binding of the cross-bridges in a weak binding state.

Actins↗
PubMed1995

Proteins reacting with anti-spectrin antibodies are present in Chlamydomonas cells.

It was found either in Western-blot analysis or in indirect immunofluorescence microscopy that cells of the alga Chlamydomonas reinhardhi contain polypeptides cross-reacting with antibodies directed against red blood cell spectrin. The protein could also be detected by immunoprecipitation with anti-spectrin antibodies. C. reinhardtii cells contain distinct polypeptide chains reacting with antibodies directed against either alpha- or beta-spectrin subunits. This protein was extracted from the cells with low ionic strength solution but was not with nonionic detergent.

Animals↗
PubMed1995

Proteins reacting with anti-spectrin antibodies are present in Chlamydomonas cells.

It was found either in Western-blot analysis or in indirect immunofluorescence microscopy that cells of the alga Chlamydomonas reinhardtii contain polypeptides cross-reacting with antibodies directed against red blood cell spectrin. The protein could also be detected by immunoprecipitation with anti-spectrin antibodies. C. reinhardtii cells contain distinct polypeptide chains reacting with antibodies directed against either alpha- or beta-spectrin subunits. This protein was extracted from the cells with low ionic strength solution but was not with nonionic detergent.

Animals↗
PubMed1995

Myosin structure/function: a combined mutagenesis-crystallography approach.

In the past year, the structure of the regulatory domain of scallop myosin has joined that of the chicken skeletal muscle myosin subfragment 1 and provided insights into the regulation of myosin function. Mutagenesis studies in a variety of systems have used the information provided by these structures to create mutant myosins to test models of chemomechanical transduction and its regulation.

Adenosine Triphosphate↗
PubMed1995

Normal modes as refinement parameters for the F-actin model.

The slow normal modes of G-actin were used as structural parameters to refine the F-actin model against 8-A resolution x-ray fiber diffraction data. The slowest frequency normal modes of G-actin pertain to collective rearrangements of domains, motions that are characterized by correlation lengths on the order of the resolution of the fiber diffraction data. Using a small number of normal mode degrees of freedom (< or = 12) improved the fit to the data significantly. The refined model of F-actin shows that the nucleotide binding cleft has narrowed and that the DNase I binding loop has twisted to a lower radius, consistent with other refinement techniques and electron microscopy data. The methodology of a normal mode refinement is described, and the results, as applied to actin, are detailed.

Actins↗
PubMed1995

[Results of resection and adjuvant therapy of liver metastases of primary colorectal tumors--a review of the literature].

Natural history of patients with colorectal liver metastases is not significantly changed even by curative resection. The majority unfortunately relapse. The results of adjuvant treatment after resection were evaluated by analysis of 17 publications as well as by own data (60 patients). 340 patients were either treated by intraarterial (n = 201), systemic (n = 82), intraportal (n = 29) or intraperitoneal (n = 28) chemoinfusion (5-Fluorouracil or Floxuridine). An alternative approach was the treatment with specific immunotherapy using tumor vaccination (n = 35) or monoclonal antibodies (n = 20). Morbidity of adjuvant treatment includes local (chemical hepatitis, biliary sclerosis) and systemic (diarrhea, stomatitis) side effects. Technical complications could reach a level of up to 50% in case of local administration. With exception of 6 studies no comparison with a resection only group was performed. Despite postulated increase of survival and recurrence free time with historical controls the results of current ongoing studies are needed before general use of adjuvant treatment can be recommended.

Antibodies, Monoclonal↗
PubMed1995

[Regional therapy breast cancer liver metastases].

The prognosis of patients with metastatic breast cancer in particular with an involvement of the liver has to be regarded as rather unfavourable. Up today no convincing therapy for patients with breast cancer and liver metastases could be found. From 1982 to 1991 42 patients with suspicion on liver metastases of a primary breast cancer were laparotomized. At that time 20 patients already had an extrahepatic formation of metastases. In contrast to the preexaminations an histologically benign liver tumor was intraoperatively verified in 6 patients. In the other 36 patients the operation was finished in 9 cases as explorative laparotomy (group A) because of extensive intra- and extrahepatic manifestation and/or vessel abnormalities. In 19 cases an arterial catheter system with subcutaneous port was implanted (group B). Partial liver resection combined with intraarterial catheter implantation was performed in 8 patients (group C). Postoperatively 27 patients monthly received a regional combined chemotherapy (groups B+C); a modified FAM scheme (5-Fluorouracil: 1000 mg/12 h/d/2 d, Adriamycin: 20 mg/12 h/d/3 d, Mitomycin C: 10 mg/2 h/d/1 d) was used. Response could be documented in 12 out of 17 evaluable patients (70.6%). A median overall postoperative survival time of 14.5 months for all patients in case of a proved liver metastases was calculated. A prolongation could not be realized, neither in patients with partial liver resection with regional therapy (group C) nor in patients with an intraarterial chemotherapy (group B). Only in exceptional cases a successful regional chemotherapy could influence the course favourable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

How cytokines control immunoglobulin class switching.

B lymphocytes can alter the class of antibody they produce by immunoglobulin class switch recombination. This recombination is targeted by distinct cytokines to particular switch regions. Prior to switch recombination, the same cytokines induce transcription through the targeted switch regions and generate IH "switch" transcripts. To show whether the two events are functionally related, we have replaced the endogenous interleukin-4 (IL-4) dependent promoter of murine I gamma 1 switch transcripts by an heterologous promoter, the human metallothionein IIA (hMT) promoter. Indeed, switch recombination can be targeted to IgG1 by the hMT promoter. In mutant mice, which cannot generate processed switch transcripts, switch recombination cannot be targeted to IgG1 by the hMT promoter. Thus, IL-4 targets switch recombination to IgG1 by induction of processed switch transcripts.

Animals↗
PubMed1995

[The malignancy potential of colorectal polyps--histomorphometric, histochemical and immunohistochemical study of the dysplasia-carcinoma sequence].

Colorectal polyps are usually diagnosed endoscopically and are simultaneously removed. Since adenomatous polyps tend to become malignant, these deserve special attention. In order to prevent carcinomas arising from pre existing adenomas, a precise analysis of the lesions in the mucous membrane of the polyps with regard to their malignancy potential is very important. Morphometric methods and determination of proliferation kinetics enable the dignity of a neoplasia to be assessed. Sporadic colorectal polyps were examined to what extent the morphometric analysis of nuclear area, the silver staining of nucleolar organizer regions (AgNORs) and the immunohistochemical staining of the Ki67 antigen permit further differentiation of the growth pattern of the tumor. Tissue from 50 hyperplastic polyps, 50 tubular and 50 tubulovillous adenomas was endoscopically removed and investigated, whereas pure villous adenomas were not examined due to their relative infrequency. These tissues were compared with biopsies of normal colonic mucosa and also with invasive adenocarcinomas. The Ki67 score shows that the proliferative activity is not significantly different between normal colonic mucosa and hyperplastic polyps, however there is a noticeable difference between the proliferation of the former types and colorectal neoplasias. The staining of the NORs does not reveal differences between the various grades of dysplasia in the adenomas, and therefore proves to be inadequate for differentiation, whereas morphometric and immunohistochemical measurements reveal appreciable selectivity. No correlation is observed between the parameters from the morphometric, histochemical and immunohistochemical analysis. Using the methods mentioned above the dysplasia-carcinoma-sequence can be clearly differentiated, however the validity of the different measurements is very variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗