Analogs of glucose-dependent insulinotropic polypeptide with increased dipeptidyl peptidase IV resistance.
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Amino Acid Substitution↗
Biomedical subjects
T Hoffmann
Publications and source records attributed to T Hoffmann.
ILT receptors at the interface between lymphoid and myeloid cells.
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B-Lymphocyte Subsets↗
Synthetic singlet oxygen quenchers.
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Alkenes↗
Treatment of solid tumors following allogeneic bone marrow transplantation.
Second solid tumors are well known late complications after bone marrow transplantation. Treatment strategies are ill defined. We retrospectively evaluated treatment and outcome in a single institution. From August 1974 to July 1996, six solid tumors were observed in five of 387 patients 2 to 13 years after BMT, corresponding to a probability of developing a second solid tumor of 9% (1-17%, 95 CI) at 15 years: these comprised endometrial carcinoma, carcinoma of the thyroid gland, cervical carcinoma, sarcoma of the small intestine, osteosarcoma of the tibia and ovarian carcinoma. All five patients were treated as intensively as they would be without a history of BMT. At last follow-up four of the five patients were alive and without signs of tumor. We postulate that second solid tumors after BMT should be treated as de novo tumors. Early detection based on consequent clinical follow-up of the transplant patients might explain the relatively good outcome.
Adenocarcinoma↗
Natural killer-type receptors for HLA class I antigens are clonally expressed in lymphoproliferative disorders of natural killer and T-cell type.
In recent years, natural killer (NK) cells, as well as subpopulations of T cells, have been found to express diverse NK receptors (NKRs) for HLA class I molecules. We have characterized NKR phenotypes in lymphoproliferative disorders of NK or T-cell type. Peripheral blood of patients with lymphoproliferative disorders (n = 9) was analysed by multiparametric immunofluorescence flow cytometry with eight different antibodies against NKRs. Abnormal neoplastic cell populations from different types of NK or T-cell lymphoproliferative disorders lacked diversity in their NKR repertoires, i.e. all or none of the abnormal cells expressed individual NKRs and this expression occurred at single levels of intensity. This pattern of expression was specific for lymphoproliferative disorders as these resticted NKR repertoires were not found either in healthy donors (n = 9) or in patients with viral or autoimmune disease (n = 5). We conclude that NKRs are clonally expressed in lymphoproliferative disorders of NK or T-cell origin. NKR repertoires may represent a novel tool in diagnosing clonal disorders of NK and T-cell type.
CD3 Complex↗
[Pre- and postoperative evaluation of ventricular function, muscle mass and valve morphology by magnetic resonance tomography in Ebstein's anomaly].
PURPOSE: To evaluate the value of MRT with spin echo (SE) and CINE gradient echo (GE) sequences for the pre- and postoperative assessment of patients with Ebstein's anomaly. METHODS: Twelve patients within the ages of four to 49 years (mean 22 +/- 12 years) were examined pre- (n = 5) or postoperatively (n = 7) after tricuspid valve reconstruction with a 1.5 T scanner. For the anatomical assessment, an ECG-gated transverse SE-sequence, for the assessment of valve morphology and function as well as for volumetry a CINE GE-sequence with retrospective gating was used. With the use of the multislice-multiphase technique, after summing up the manually outlined epi- and endocardial areas, endsystolic (ESV) and enddiastolic volumes (EDV), ejection fraction (EF), stroke volume (SV), and muscle mass (MM) were calculated for both ventricles. RESULTS: The differentiation of the displaced parts of the tricuspid valve (TV) was insufficient with static SE, but was possible in all patients with CINE-MRT. Like in Doppler echocardiography, a qualitative assessment of tricuspid insufficiency was possible in CINE-MRT, the mean incompetence grade preoperative was 1.8 (+/- 0.8), postoperative 0.7 (+/- 0.5). The mean RV-EF in the preoperative group was 41.8% (+/- 6.4), in the postoperative group 47.9% (+/- 10.6), the mean LV-EF preoperative 47.4% (+/- 8.5%), postoperative 63.0% (+/- 9.4). CONCLUSION: CINE-MRT should rather be used than SE for the assessment of valve morphology. EF, muscle mass and tricuspid incompetence can also be calculated pre- and postoperative with CINE-MRT.
Adolescent↗
Fermentative metabolism of Bacillus subtilis: physiology and regulation of gene expression.
Bacillus subtilis grows in the absence of oxygen using nitrate ammonification and various fermentation processes. Lactate, acetate, and 2,3-butanediol were identified in the growth medium as the major anaerobic fermentation products by using high-performance liquid chromatography. Lactate formation was found to be dependent on the lctEP locus, encoding lactate dehydrogenase and a putative lactate permease. Mutation of lctE results in drastically reduced anaerobic growth independent of the presence of alternative electron acceptors, indicating the importance of NADH reoxidation by lactate dehydrogenase for the overall anaerobic energy metabolism. Anaerobic formation of 2,3-butanediol via acetoin involves acetolactate synthase and decarboxylase encoded by the alsSD operon. Mutation of alsSD has no significant effect on anaerobic growth. Anaerobic acetate synthesis from acetyl coenzyme A requires phosphotransacetylase encoded by pta. Similar to the case for lctEP, mutation of pta significantly reduces anaerobic fermentative and respiratory growth. The expression of both lctEP and alsSD is strongly induced under anaerobic conditions. Anaerobic lctEP and alsSD induction was found to be partially dependent on the gene encoding the redox regulator Fnr. The observed fnr dependence might be the result of Fnr-induced arfM (ywiD) transcription and subsequent lctEP and alsSD activation by the regulator ArfM (YwiD). The two-component regulatory system encoded by resDE is also involved in anaerobic lctEP induction. No direct resDE influence on the redox regulation of alsSD was observed. The alternative electron acceptor nitrate represses anaerobic lctEP and alsSD transcription. Nitrate repression requires resDE- and fnr-dependent expression of narGHJI, encoding respiratory nitrate reductase. The gene alsR, encoding a regulator potentially responding to changes of the intracellular pH and to acetate, is essential for anaerobic lctEP and alsSD expression. In agreement with its known aerobic function, no obvious oxygen- or nitrate-dependent pta regulation was observed. A model for the regulation of the anaerobic fermentation genes in B. subtilis is proposed.
Acetates↗
Kinetic analysis of enzymatic and nonenzymatic degradation of peptides by MALDI-TOFMS.
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Animals↗
Metabolic diseases and their possible link to risk indicators of periodontitis.
BACKGROUND: During the last few years, risk assessment has become one of the main topics of periodontal research. Therefore, the aim of this study was to determine whether a predisposition to metabolic disorders such as diabetes mellitus (in the absence of diagnosed diabetic disease) or hyperlipidemia may be risk indicators for periodontitis. METHODS: One hundred patients ranging in age from 40 to 70 years were examined. The patients were classified as having impaired glucose tolerance (IGT) but no manifest diabetes (56 patients), hyperlipidemia (17 patients, HL), or normal metabolic status (27 control patients). Probing depth (PD), attachment level (AL), plaque index (PI), and gingival bleeding on probing (BOP) were recorded. Serum antibody titers (SAT) to A. actinomycetemcomitans (A.a.), P. intermedia (P.i.), and P. gingivalis (P.g.) were determined by enzyme-linked immunosorbent assay (ELISA). Pooled subgingival plaque samples were analyzed using indirect immunofluorescence to detect the same organisms. In addition, respiratory burst activity of peripheral polymorphonuclear leukocytes (PMN) was evaluated by chemiluminescence (CL). RESULTS: No significant differences were observed between the IGT group and normal controls in the following parameters: 1) percentage of sites exhibiting BOP; 2) mean PI; 3) mean PD and AL; 4) percentage of periodontal microorganisms; and 5) increased SAT. The IGT probands exhibited a significantly higher mean serum level of triglycerides, as well as higher formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMN chemiluminescence than the control group. Patients with hyperlipidemia (HL) showed a significantly higher number of sextants with increased PD (73.4%) than the control group (50.6%). Similar results were obtained when comparing the percentage of all sites with increased PD (HL = 16.7%, control 12.3%). The mean FMLP-stimulated CL in patients with hyperlipidemia was significantly higher than the control group. When looking at all patients, there was a small but statistically significant correlation between PD and lipid levels. In addition, a significant correlation was observed between lipid serum levels and the FMLP-stimulated chemiluminescence. CONCLUSIONS: These findings suggest that abnormal glucose tolerance, which is a predisposing factor for diabetes mellitus, does not appear to be a risk indicator for periodontal disease. On the other hand, impaired lipid metabolism does seem to be a risk indicator for periodontitis.
Adult↗
Application of gas chromatography-cryocondensation-Fourier transform infrared spectroscopy and gas chromatography-mass spectrometry to the identification of gas phase reaction products from the alpha-pinene/ozone reaction.
The gas phase reaction of alpha-pinene with the atmospheric oxidant ozone was investigated by using the capabilities of both gas chromatography-cryocondensation-Fourier transform infrared spectroscopy (GC-FT-IR) and gas chromatography-mass spectrometry (GC-MS), for the identification of the reaction products formed. The reaction was carried out in a flow reaction chamber from where the compounds were sampled on Tenax-containing adsorption cartridges. The reaction mixture was injected onto the column after thermodesorption and analyzed using both GC-IR and GC-MS. Twenty compounds could be detected, including the reactant alpha-pinene and it's impurities tricyclene and camphene. Eleven compounds were identified by spectra comparison with either reference data or spectra obtained from commercial standards. Four compounds were tentatively identified from their IR and MS spectra, while from the remaining two compounds the nature of basic functional groups could be established.
Bicyclic Monoterpenes↗
Evidence for a crucial role of neutrophil-derived serine proteases in the inactivation of interleukin-6 at sites of inflammation.
The bioactivity of interleukin-6 (IL-6) was found to be dramatically reduced in fluids from sites of inflammation. Here, we provide evidence that the neutrophil-derived serine proteases elastase, proteinase 3 and cathepsin G are mainly involved in its degradation and subsequent inactivation. The initially hydrolyzed peptide bonds were detected to be Val(11)-Ala(12) and Leu(19)-Thr(20) (elastase), Phe(78)-Asn(79) (cathepsin G) and Ala(145)-Ser(146) (proteinase 3). The soluble IL-6 receptor elicits a protective effect against the IL-6 inactivation by cathepsin G only. The inactivation of IL-6 by neutrophil-derived serine proteases might act as a feedback mechanism terminating the IL-6-induced activation of neutrophils.
Cathepsin G↗
Graft-versus-myeloma after withdrawal of immunosuppression following allogeneic peripheral stem cell transplantation.
There is growing evidence for a graft-versus-myeloma effect following allogeneic stem cell transplantation. We add to this evidence by reporting complete remission achieved by withdrawal of immunosuppression in a patient with multiple myeloma progressing after HLA-identical sibling peripheral stem cell transplantation. De novo chronic graft-versus-host disease coincided with the anti-myeloma effect and responded to treatment. The patient remains in complete remission 3 years after transplant.
Adult↗
Repeated peripheral stem cell mobilization in healthy donors: time-dependent changes in mobilization efficiency.
Mobilization of peripheral blood stem cells was analysed in 10 consecutive healthy donors undergoing repeated stem cell mobilization for allogeneic transplantation. Donors received recombinant G-CSF at a dose of 10 microg/kg/d for both mobilizations. Collection of stem cells was started on day 5 of G-CSF administration. To compare the efficiency of first and second mobilization, we determined the leucocyte and CD34+ cell counts in peripheral blood, and the yield of nucleated cells and CD34+ cell counts in the apheresis product. CD34+ cell numbers in peripheral blood were (median) 81.2 x 10(6)/l during the first and 50.4 x 10(6)/l during the second mobilization (P = 0.007). Likewise, CD34+ cells in the apheresis product decreased from 319.8 x 10(6) to 275.7 x 10(6) (P = 0.02). Decrease in CD34+ cell counts in peripheral blood and in the apheresis product was associated with the time interval between first and second mobilization. In a regression analysis there was a correlation between the ratios of CD34+ cell counts of first and second mobilization and the inverse of time interval between procedures (r2 = 0.51 peripheral blood; r2 = 0.74 apheresis product). Thus, stem cell yield is reduced when healthy donors receive repeated mobilization within a short time. Nevertheless, an adequate number of stem cells may repeatedly be mobilized within 2 months.
Antigens, CD34↗
Diaspirin cross-linked hemoglobin effectively restores pancreatic microcirculatory failure in hemorrhagic shock.
BACKGROUND: Microvascular reperfusion failure of splanchnic organs is a crucial hallmark in organ damage induced by hemorrhagic shock, which should be prevented by a resuscitation solution. Because the vasoactive properties of the hemoglobin-based oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) could adversely influence restoration of pancreatic capillary perfusion during resuscitation, the authors investigated its effects on the microcirculation of the rat pancreas in comparison with whole blood and 6% hydroxyethylstarch resuscitation from severe hemorrhagic shock. METHODS: Twenty-eight pentobarbital-anaesthetized rats were bled to a mean arterial pressure (MAP) of 40 mmHg and maintained at this level for 1 h. Using an intravital microscope, mean arterial pressure, the length of erythrocyte-perfused pancreatic capillaries per observation area (functional capillary density), the adherence of leukocytes in postcapillary venules, and pancreatic lipid peroxidation, measured as thiobarbituric acid-reactive material in pancreatic tissue, were determined in animals resuscitated by volumes of hydroxyethylstarch, DCLHb, and whole blood (WB) equivalent to the shed blood volume or in control animals without shock induction for a period of 2 h after resuscitation. RESULTS: Compared with control animals (366+/-28 cm(-1)), animals resuscitated with DCLHb (294+/-45 cm(-1)), WB (306+/-11 cm(-1)), and hydroxyethylstarch (241+/-34 cm(-1)) showed a significant reduction of functional capillary density after 2 h of resuscitation. DCLHb was as effective as WB and superior to hydroxyethylstarch in restoring functional capillary density and mean arterial pressure. Leukocyte adherence in postcapillary venules was not enhanced by DCLHb (369+/-148/mm2) infusion when compared with hydroxyethylstarch- (615+/-283/mm2) and WB-treated (510+/-415/mm2) animals. Lipid peroxidation of pancreatic tissue was significantly elevated after treatment with both oxygen-carrying solutions compared with hydroxyethylstarch. CONCLUSION: DCLHb is as effective as WB for preservation of the pancreatic microcirculation.
Acid-Base Equilibrium↗
Effect of diaspirin cross-linked hemoglobin on normal and postischemic microcirculation of the rat pancreas.
Microcirculatory alterations with reduced nutritive supply to the pancreas could be the cause of hyperamylasemia, which occurs in some patients receiving the vasoactive oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) in clinical studies. Therefore, the effects of DCLHb on rat pancreas microcirculation were evaluated. Anesthetized Sprague-Dawley rats received one of the following treatments during baseline conditions (n = 7 rats/group): 10% hydroxyethyl starch (HAES) (0.4 ml/kg), DCLHb (400 mg/kg), or DCLHb (1,400 mg/kg). After 1 h of complete, reversible pancreatic ischemia, other animals received 10% HAES (0.4 ml/kg) or DCLHb (400 mg/kg) during the onset of reperfusion. The number of red blood cell-perfused capillaries (functional capillary density, FCD) and the level of leukocyte adherence in postcapillary venules in the pancreas were assessed by means of intravital microscopy during 2 h after treatment. In the nonischemic groups, FCD was 18% greater after DCLHb (1,400 mg/kg) than after 10% HAES treatment without any increase in leukocyte adherence. In the inschemia-reperfusion (I/R) 10% HAES group, FCD was significantly (P < 0.05) lowered, leukocyte adherence enhanced, and mean arterial pressure (MAP) reduced by 31% compared with nonischemic animals. DCLHb treatment in the I/R group resulted in a slight increase in FCD, a significant (P < 0.05) reduction of leukocyte adherence, and a complete restoration of MAP compared with the animals of the I/R control group. Thus our data provide no evidence for a detrimental effect on the pancreatic microcirculation or an enhanced risk of postischemic pancreatitis by DCLHb.
Animals↗
Inhibition of neutrophil proteinases by recombinant serpin Lex032 reduces capillary no-reflow in ischemia/reperfusion-induced acute pancreatitis.
Because neutrophil proteinases such as elastase and cathepsin G are considered to play a major role in inflammatory tissue damage, the microcirculatory effect of the serine proteinase inhibitor (serpin) Lex032 after ischemia/reperfusion (I/R)-induced pancreatitis was investigated. Lex032 inhibits these proteinases by recombinant combination of alpha(1)-antitrypsin and alpha(1)-antichymotrypsin. Twenty-eight anesthetized rats received either Lex032 or NaCl 0.9% as a control solution during baseline conditions or after 1 h of complete reversible ischemia induced by microclip occlusion of the pancreatic arteries. The number of erythrocyte-perfused capillaries (functional capillary density) and the leukocyte adherence in postcapillary venules were assessed by intravital microscopy 45, 90, and 120 min after administration. In the baseline group, Lex032 increased leukocyte adherence compared with the NaCl 0.9% baseline group, without changing any other parameter. I/R without Lex-032 treatment resulted in a 50% reduction in functional capillary density, a 2-fold increase in leukocyte adherence, an increase in interleukin-6 serum concentration, and a significant fall in blood pressure during reperfusion time compared with baseline animals. Treatment with Lex032 in I/R resulted in significant preservation of capillary perfusion, an absence of interleukin-6 increase, and preservation of mean arterial pressure during reperfusion time, without changing the leukocyte adherence, compared with the NaCl 0.9% I/R group. Because of its considerable amelioration of microcirculatory perfusion, Lex032 might be useful in the treatment of pancreatic I/R tissue damage (e.g., cardiac bypass surgery, pancreas transplantation, and hemorrhagic shock) by prevention of capillary perfusion failure.
Acid-Base Equilibrium↗
[25 years allogenic bone marrow transplantation in Basel: 1973-1998].
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Bone Marrow Transplantation↗
[Establishing an umbilical cord blood bank for unrelated allogenic stem cell transplantation].
We report the establishment of a cord-blood bank in a routine hematological laboratory. Cord-blood collection was performed with placenta in utero by a trained team and immediately sent to the cord-blood bank. There, 6.8 ml cord-blood was used for analysis of nucleated cell counts, counts of CD34-positive cells, CFU's, complete HLA-typing, ABO and Rhesus blood groups, bacteriologic cultures and serology for HIV 1 and 2, HbsAg, HVC, CMV, syphilis and toxoplasmosis. The cord-blood collection was frozen and conserved at -192 degrees C. From each cord-blood vials of DNA, viable cells and plasma were cryopreserved. Between June 1997 and April 1998, 54 cord-bloods were collected. 40 of them were cryo-preserved, and 14 discarded because of low cell counts. The median volume was 109 ml with 1.4 x 10(9) nucleated cells. The in vitro capacity of proliferation of the cord-blood correlated well with the absolute counts of CD34-positive cells (r = 0.93), moderately with the relative counts of CD34 (r = 0.68) as well as the nucleated cells (r = 0.70), poorly with the volume (r = 0.44). Three of the 40 (7.5%) cord-blood products contained a bacterial contamination. This study shows that a cord-blood bank can be organised in a routine hematological laboratory, which is familiar with transplantation products. However, the procedure is time consuming, expensive and requires a highly qualified team and specialised technical equipment.
Blood Banks↗