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A Kramer

Publications and source records attributed to A Kramer.

At least 127 records · Page 7Linked to original sources
PubMed1996

Mapping protein-protein contact sites using cellulose-bound peptide scans.

We have characterized the interaction of two monoclonal antibodies with their respective antigens using cellulose-bound sets of overlapping peptides (peptide scans). Both antibodies CB/RS/5 and CB/MT/1 recognize discontinuous epitopes present in human interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-alpha). In addition, the interaction between TNF-alpha and its 55-kDa receptor (TNF-R) was investigated by the same approach. Both antibodies, as well as TNF-alpha, interacted with two or more regions of the peptide scans. Antibody-binding competition studies between the native antigens and peptides, covering single parts of the binding regions, enabled us to distinguish between binding to the paratope or other regions of the antibody. The combination of these experimental approaches allowed the identification of short antigen-derived sequences that are separated on the primary sequence but close in space on the surface of IL-10 and TNF-alpha, thus representing putative discontinuous epitopes. In the case of the TNF-R-derived peptide scans, two of the identified regions interact with the structurally similar TNF-beta in the TNF-beta-TNF-R complex. These data indicate that this approach should be generally applicable for mapping nonlinear protein-protein contact sites.

Amino Acid Sequence↗
PubMed1996

[Current state of alimentary iodine deficiency in Germany].

Germany finds itself among the most iodine deficient countries of Europe. Voluntary use of iodized salt constitutes the only goiter prophylaxis. In the last few years, measures such as the opening up of European internal markets, abolition of lac pertaining to the alimentary iodine consumption. Random samples of urine collected from 5932 persons without thyroid ailment, distributed over 32 regions of Germany, were measured for iodine excretion. The median value of iodine excretion was 72.4 micrograms I/g creatinine. Children under 10 years (76.9) and persons over 70 years (80.7) showed a slightly higher iodine elimination than those between 11-70 years (71.9). No differences between the former East Germany and West Germany as well as North, South and middle regions of unified Germany were observed. 55% of the study population presented with iodine values between 50 and 100 micrograms, 19% with lower than 50 micrograms. Only 9% showed sufficient iodine state. The results expose the inadequacy of the voluntary measures to tackle the problem of alimentary iodine deficiency.

Adolescent↗
PubMed1996

The clinical practice developmental model: the transition process.

The authors report their hospital's experience in replicating Benner's novice-to-expert clinical nursing practice model, called the Clinical Practice Developmental Model. The authors describe the outcomes of an exploratory, qualitative study conducted to understand staff nurses' perceptions of their transition experience from a traditional clinical ladder for advancement and recognition to the theoretically based clinical practice developmental model. The findings of this study identify critical factors that influenced nurses' perceptions and describe positive and negative outcomes of transition. Specific recommendations to facilitate organizational changes for the nurse executive and the individual nurse are discussed.

Adult↗
PubMed1996

Compartmentalized lung cytokine release in response to intravascular and alveolar endotoxin challenge.

Lung cytokine generation has been implicated in pulmonary injury and systemic inflammatory responses. In bufferperfused rabbit lungs, intravascular endotoxin (10 ng/ml perfusate; total amount 7 micrograms) provoked the liberation of 212,100 +/- 119,700 pg tumor necrosis factor-alpha (TNF-alpha) into the vascular space within 3 h. This was augmented to 3,564,400 +/- 1,285,900 pg in the presence of 1% serum. Bronchoalveolar lavages demonstrated the absence of buffer-admixed endotoxin and transition of only minor fractions of the vascular TNF-alpha load into the alveolar space. Aerosolization of 22 micrograms endotoxin liberated 824,400 +/- 48,750 pg TNF-alpha into the alveolar compartment, which was even increased to 16,980,000 +/- 6,066,350 pg on co-nebulization of serum. No endotoxin and only minor amounts of the alveolar TNF-alpha burden spilled over into the vascular compartment. Vascular pressures and lung vascular permeability did not change. We conclude that both intravascular and alveolar endotoxin challenge provokes excessive lung TNF-alpha generation, amplified manyfold in the presence of small serum quantities. For both routes of application, however, the cytokine responses were found to be largely compartmentalized under the given conditions of integer lung barrier properties.

Aerosols↗
PubMed1995

Ca2+ influx induced by store release and cytosolic Ca2+ chelation in Ht29 colonic carcinoma cells.

Cl- secretion in HT29 cells is regulated by agonists such as carbachol, neurotensin and adenosine 5'-triphosphate (ATP). These agonists induce Ca2+ store release as well as Ca2+ influx from the extracellular space. The increase in cytosolic Ca2+ enhances the Cl- and K+ conductances of these cells. Removal of extracellular Ca2+ strongly attenuates the secretory response to the above-mentioned agonists. The present study utilises patch-clamp methods to characterise the Ca2+ influx pathway. Inhibitors which have been shown previously to inhibit non-selective cation channels, such as flufenamate (0.1 mmol.l-1, n = 6) and Gd3+ (10 micromol.l-1, n=6) inhibited ATP (0.1 mmol.l-1) induced increases in whole-cell conductance (Gm). When Cl- and K+ currents were inhibited by the presence of Cs2SO4 in the patch pipette and gluconate in the bath, ATP (0.1 mmol.l-1) still induced a significant increase in Gm from 1.2 +/- 0.3 nS to 4.7 +/- 1 nS (n = 24). This suggests that ATP induces a cation influx with a conductance of approximately 3-4 nS. This cation influx was inhibited by flufenamate (0.1 mmol.l-1, n = 6) and Gd3+ (10 micromol.l-1, n = 9). When Ba2+ (5 mmol.l-1) and 4,4'-diisothiocyanato-stilbene-2-2'-disulphonic acid (DIDS, 0.1 mmol.l-1) were added to the KCl/K-gluconate pipette solution to inhibit K+ and Cl- currents and the cells were clamped to depolarised voltages, ATP (0.1 mmol.l-1) reduced the membrane current (Im) significantly from 86 +/- 14 pA to 54 +/- 11 pA (n = 13), unmasking a cation inward current. In another series, the cation inward current was activated by dialysing the cell with a KCl/K-gluconate solution containing 5-10 mmol.l-1 1,2-bis-(2-aminoethoxy)ethane-N,N,N',N'-tetraacetic acid (EGTA) or 1,2-bis-(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA). The zero-current membrane voltage (Vm) and Im (at a clamp voltage of +10 mV) were monitored as a function of time. A new steady-state was reached 30-120 s after membrane rupture. Vm depolarised significantly from -33 +/- 2 mV to -12 +/- 1 mV, and Im fell significantly from 17 +/- 2 pA to 8.9 +/- 1.0 pA (n = 71). This negative current, representing a cation inward current, was activated when Ca2+ stores were emptied and was reduced significantly ( Im) when Ca2+ and/or Na+ were removed from the bathing solution: removal of Ca2+ in the absence of Na+ caused a Im of 5.0 +/- 1.2 pA (n = 12); removal of Na+ in the absence of Ca2+ caused a Im of 12.8 +/- 3.5 pA (n = 4). The cation inward current was also reduced significantly by La3+, Gd3+, and flufenamate. We conclude that store depletion induces a Ca2+/Na+ influx current in these cells. With 145 mmol.l-1 Na+ and 1 mmol.l-1 Ca2+, both ions contribute to this cation inward current. This current is an important component in the agonist-regulated secretory response.

Adenosine Triphosphate↗
PubMed1995

Polarized ion transport during migration of transformed Madin-Darby canine kidney cells.

Epithelial cells lose their usual polarization during carcinogenesis. Although most malignant tumours are of epithelial origin little is known about ion channels in carcinoma cells. Previously, we observed that migration of transformed Madin-Darby canine kidney (MDCK-F) cells depended on oscillating K+ channel activity. In the present study we examined whether periodic K+ channel activity may cause changes of cell volume, and whether K+ channel activity is distributed in a uniform way in MDCK-F cells. After determining the average volume of MDCK-F cells (2013+/-270 microm3; n=8) by means of atomic force microscopy we deduced volume changes by calculating the K+ efflux during bursts of K+ channel activity. Therefore, we measured the membrane conductance of MDCK-F cells which periodically rose by 22.3+/-2.5 nS from a resting level of 6.5+/-1.4 nS (n=12), and we measured the membrane potential which hyperpolarized in parallel from -35.4+/-1.2 mV to -71.6+/-1.8 mV (n=11). The distribution of K+ channel activity was assessed by locally superfusing the front or rear end of migrating MDCK-F cells with the K+ channel blocker charybdotoxin (CTX). Only exposure of the rear end to CTX inhibited migration providing evidence for "horizontal" polarization of K+ channel activity in transformed MDCK-F cells. This is in contrast to the "vertical" polarization in parent MDCK cells. We propose that the asymmetrical distribution of K+ channel activity is a prerequisite for migration of MDCK-F cells.

Animals↗
PubMed1995

A general route to fingerprint analyses of peptide-antibody interactions using a clustered amino acid peptide library: comparison with a phage display library.

We provide a general route to fingerprint analyses of peptide-antibody interactions using a novel chemically synthesized peptide library. A combinatorial clustered amino acid peptide library XO1O2O3O4X (O = one of six amino acid clusters [APG], [DE], [HKR], [NQST], [FYW] and [ILVM]; X = randomized position) bound to a continuous cellulose membrane support was designed to overcome the problem of combinatorial explosion in the synthesis of peptide libraries. This library served as the starting point for the identification and detailed characterization of a TGF alpha peptide epitope recognized by the antibody Tab2. By analysing 1728 hexapeptide mixtures and 1600 single hexapeptides we identified a large number of structurally different high affinity Tab2 binding molecules. Our data provide a detailed picture of the structural basis of this antibody-peptide interaction. In addition to the detection of key amino acids involved in Tab2 binding we observed a high variability of Tab2 binding sequences supporting an induced fit mechanism in antibody-peptide recognition. In contrast, a phage display hexapeptide library led to the detection of only one dominant Tab2 binding peptide. The data obtained also demonstrate the influence of phage proteins on the interaction between the antibody and the displayed peptide. Comparing both approaches with regard to ease of handling and identified sequences, the chemical libraries are clearly favored to study antibody-peptide interactions.

Amino Acid Sequence↗
PubMed1995

Oxygen transport and cardiovascular effects of resuscitation from severe hemorrhagic shock using hemoglobin solutions.

OBJECTIVE: To test the short-term efficacy of three hemoglobin solutions in restoring cardiac output, intravascular pressures, oxygen transport (DO2), and oxygen consumption (VO2) after resuscitation from severe hemorrhagic shock. DESIGN: Prospective study. SETTING: Research laboratory. SUBJECTS: Beagle dogs. INTERVENTIONS: After anesthesia and instrumentation, hemorrhagic shock was induced for 2 hrs by blood withdrawal to maintain systolic blood pressure at 50 mm Hg. Resuscitation then occurred with one of four different resuscitation fluids. One group of dogs was not resuscitated. Survival rate was monitored for 8 days. MEASUREMENTS AND MAIN RESULTS: In 33 beagle dogs, cardiovascular variables (DO2 and VO2) were compared after resuscitation with 8% stroma-free hemoglobin, 4% or 8% pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP44 and PHP88, respectively), or autologous whole blood. The dogs were anesthetized, paralyzed, mechanically ventilated (FIO2 of 0.21), and instrumented with arterial and pulmonary artery catheters. An average of 63% of estimated blood volume was removed to maintain systolic blood pressure at 50 mm Hg for 2 hrs. The dogs then were either not resuscitated (n = 4) or resuscitated with 8% stroma-free hemoglobin (n = 7), PHP44 (n = 6), PHP88 (n = 8), or whole blood (n = 8), with a volume equivalent to the withdrawn blood. Cardiovascular variables, DO2, VO2, oxygen extraction ratios, and blood concentrations of lactic acid and catecholamines were determined before, and for < or = 6 hrs after, resuscitation from hemorrhagic shock. Blood smears were microscopically examined. In addition, the survival rate was monitored for 8 days after resuscitation. By 2 hrs of hemorrhagic shock, there was a large decrease in DO2 (p < .05) and an increase in oxygen extraction ratio from 0.27 to 0.70 (p < .05). There was a 3.5-fold increase in lactate concentrations and a 25-fold increase in catecholamine concentrations as compared with preshock values. All dogs not resuscitated died within 1.75 hrs after 2 hrs of shock. After resuscitation with whole blood, all cardiovascular and oxygen transport variables returned to approximately prehemorrhage values and remained so throughout the measurement period. After resuscitation with any hemoglobin solution, DO2 returned transiently to control values. However, recovery of DO2 was short-lived in all hemoglobin solution groups, and, by 4 hrs postresuscitation in all groups, DO2 was less than the DO2 of the dogs receiving whole blood (p < .05). These changes were associated with decreases in total hemoglobin concentrations compared with the values immediately before resuscitation (p < .05). In addition, with resuscitation using the PHP solutions, blood smears demonstrated aggregation of red blood cells and platelets. On day 8 after hemorrhagic shock, the survival rate was 100% for whole blood and PHP44, 86% for 8% stroma-free hemoglobin, and 33% for PHP88. CONCLUSIONS: Resuscitation from severe hemorrhagic shock with 8% stroma-free hemoglobin, PHP44, or PHP88 is equally effective in restoring cardiac index and vascular pressures as using whole blood. However, resuscitation with the three hemoglobin solutions only transiently restored DO2 after hemorrhagic shock. The subsequent reduction of DO2 compared with the DO2 value using whole blood was due mostly to hemodilution. With the two PHP solutions, formation of red blood cell aggregates probably resulted in sequestration of red cell mass and additional loss of oxygen carrying capacity.

Animals↗
PubMed1995

[Lactoperoxidase activity and thiocyanate content of milk from cows with mastitis in different lactation stages].

During three lactational periods (start, middle and end of lactation) of 35 milk cows suffering from mastitis and compared with 34 healthy milk cows of comparable milk production the activity of lactoperoxidase (LPO) and the SCN-content of the milk in each udder quarter were determined. Both components showed no alterations in the subclinical form of the disease. There exists a decrease of the LPO activity in the secretion of ill udder quarters, which will be distinct only in the individual animal and a strong increase of the SCN-content, which is also significant in comparison with the milk of healthy cows.

Animals↗
PubMed1995

[Thiocyanate content in blood plasma, udder lymph and milk from healthy cows and cows with mastitis].

After storage for more than one year the SCN(-)-content of udder lymph was not changed seriously, but in blood serum and mainly in milk, there is an evident decrease. In lactational cows with healthy udders the SCN(-)-content of blood plasma is higher than in milk (in average twice). There is no difference of the SCN(-)-content of the four udder parts of healthy cows. Decrease of milk production (10. to 13. lactational month) causes an increase of the SCN(-)-content of the milk, it is not changed in subclinical mastitis. In lactational cows with healthy udders the SCN(-)-content of udder lymph is nearly triple higher in average than in milk of the corresponding quarter of the udder. The existence of a common compartment of SCN- in blood and udder lymph is assumed, which is separated from them of the milk by the blood udder barrier.

Animals↗
PubMed1995

[Hypothenar hammer syndrome].

Hypothenar hammer syndrome is an infrequently diagnosed labor disease. We report a 51 years old male who used the medial aspect of his left hand as a hammer over the past 12 years. He presented with an ipsilateral ring finger embolization. An angiogram demonstrated an ulnar artery occlusion at the hypothenar eminence. No other source of emboli was found and treatment was conservative. This disease is a consequence of repetitive trauma on the ulnar artery, that leads to vessel wall changes and promotes local thrombosis, distal embolization and eventually, occlusion in situ. Treatment options are conservative in case of occlusion or reconstruction with exclusion of the emboligeneous area.

Arterial Occlusive Diseases↗
PubMed1994

[Current aspects of antisepsis in dermatology and venereology].

Resulting from the infectiologically established novel definition of antiseptic which contains the local application of antiseptics for prophylactical, preventive or therapeutical indication on skin, mucous membrane, wounds, in body cavities or on surgical exposed resp. opened endosomatic areas the antiseptical indications in a branch of dermatology and venereal diseases are represented. With the analysis of the actual knowledge in vitro and in vivo requirements to local antiinfectiva are defined combined with the recommendations for the clinical use. At present mainly prophylactically used agents are submitted to an benefit risk analysis with refer to the choice of agents. There by agents for the application on skin as well as on genitals, in mouth cavity and on wounds were taken into consideration.

Anti-Infective Agents, Local↗
PubMed1994

Conjoined double internal mammary artery grafting.

Double internal mammary artery (IMA) grafting to the coronary arteries was performed on 82 patients. In ten of them one IMA was used as a free graft, and was proximally connected to the other ("conjoined" double IMA), the indications being insufficient supply of adequate veins, diseased aortic wall, availability of only a short right IMA segment for free grafting, occluded left subclavian artery, and when distal and scattered lesions of relatively important vessels had to be bypassed. Additional sequential IMA anastomoses were performed in four patients and an additional sequential vein graft in a fifth. All patients became angina-free postoperatively and have remained so during observation up to 16 months. Recatheterization studies were performed in six patients and in all of them the IMA-to-IMA (n = 6) and distal anastomoses (n = 26) were patent. Conjoined double IMA grafting is an important option available to the cardiac surgeon for management of selected patients with coronary artery disease.

Cardiac Catheterization↗