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W Neugebauer

Publications and source records attributed to W Neugebauer.

At least 19 recordsLinked to original sources
PubMed1992

Structural elements of human parathyroid hormone and their possible relation to biological activities.

Human parathyroid hormone (hPTH) and several deletion analogues were examined for the presence of secondary structure using circular dichroism spectroscopy. The spectra of hPTH and the deletion analogues 8-84, 34-53, 53-84, 1-34, 13-34, 1-19, and 20-34, in neutral, aqueous buffer, gave no evidence for extensive secondary structure. An alpha-helical-like spectral contribution was found to arise from a region within peptide 13-34. This spectral contribution was speculated to arise from partial stability of a helix consisting of residues 17-29. Molecular dynamics simulations of peptide 1-34 suggested that this peptide tends to fold with a bend defined by residues 10-14, with the amino-terminal and carboxyl-terminal residues tending to be in more extended forms and the other residues in helical-like conformations. The addition of trifluoroethanol promoted the formation of alpha-helix, mainly in the 1-34 region. The putative helix comprised of residues 17-29 was stabilized by the addition of 10-20% TFE, while a second putative helix proximal to the amino terminus, and comprised of residues 3-11, was stabilized by slightly higher concentrations of TFE. An amphiphilic sequence was identified within the 20-34 fragment. The development of alpha-helix on binding this fragment, and other analogues containing this sequence, to palmitoyloleoylphosphatidylserine vesicles provided experimental evidence for the potential role of this amphiphilic sequence in binding to membranes or to a membrane receptor. The relationships between these alpha-helical regions in 1-34, either potentiated by trifluoroethanol or lipid vesicles, are discussed in terms of different receptor-binding regions within hPTH.

Amino Acid Sequence↗
PubMed1992

Preparation and biological activities of potential vasopressin photoaffinity labels.

Several potential photoaffinity analogues of the peptide hormone vasopressin (VP) were prepared by classical solid-phase peptide synthesis using two different pathways. Peptide sequences were built by introduction of (a) Nar-protected aminophenylalanine or (b) nitrophenylalanine in the photolabeling position. Conversion to the azido peptide was completed in pathway a after cleavage and before purification and in pathway b from small quantities of purified nitrophenylalanine-containing precursor peptides. V1 receptor binding properties were measured using membranes prepared from rat liver cells. The binding potential of agonistic VP structures was abolished by the introduction of an azido or a nitro group into the aromatic side chain at position 3. Cyclo desamino-beta,beta-dialkyl-Cys1-type VP antagonist structures were prepared with the photoactivable moiety in position 2 and an iodination residue in position 9. One particular compound, [Dmpa1, Phe(N3)2, Val4, Lys8,D-Tyr9]VP (8), containing beta,beta-dimethyl-beta-mercaptopropionic acid in position 1, had excellent binding properties, both in the radioiodinated (Kd = 4.8 +/- 1.9 x 10(-10) M) and noniodinated form (Kd = 6.4 +/- 0.98 x 10(-10) M). The analogues with long-chain beta-alkylation (diethyl and pentamethylene) and the linear antagonist photolabel showed significantly less affinity. Optimal binding properties were obtained within a very narrow range of hydrophobicity; greater or lesser hydrophobicity was correlated to less potent binding. The precursor analogues, containing nitrophenylalanine, displayed a structure-activity relationship similar to that of the azido peptides. The most potent analogues will be used for receptor labeling studies. A linear antagonist structure having a photosensitive group in position 1, has also been prepared, but this compound displayed much less affinity than the cyclic antagonists. The most potent compounds were also highly selective for the V1 receptor and did not recognize the V2 receptor from other preparations.

Affinity Labels↗
PubMed1992

The protein kinase-C activation domain of the parathyroid hormone.

The PTH activates both adenylate cyclase and a mechanism that increases membrane-associated protein kinase-C (PKC) activity. To define the hormone's PKC activation domain we have used a panel of PTH fragments and ROS 17/2 rat osteosarcoma cells as the target cells. PTH equally and maximally increased PKC activity in ROS 17/2 cell membranes at physiological concentrations between 1-50 pM and 5-50 nM, but not at intermediate concentrations or concentrations above 50 nM. The PKC-stimulating picomolar concentrations of PTH did not stimulate adenylate cyclase in ROS 17/2 cells, while the PKC-stimulating nanomolar concentrations of the hormone did stimulate adenylate cyclase, with an EC50 of 1-2 nM. Very high concentrations of PTH, such as 100 nM, that did not increase membrane PKC activity were still able to maximally stimulate adenylate cyclase. PTH fragments lacking the N-terminal amino acids needed for adenylate cyclase activation increased membrane PKC activity, and the PKC activation domain was found to lie within the 28-34 region of the PTH molecule. This was confirmed by showing that optimally effective picomolar concentrations of the human PTH-(28-34) fragment itself were able to increase membrane-associated PKC activity to the same extent as the optimally effective picomolar concentrations of the intact PTH-(1-84) or the larger PTH-(1-34) or PTH-(3-34) fragments.

Animals↗
PubMed1991

Specific degenerate codons enhanced selective expression of human parathyroid hormone in Escherichia coli.

Specific degenerate codons in the amino-terminal region of a synthetic human parathyroid hormone (PTH) gene exerted dramatic effects on both products and yield of expression of this 84-amino acid polypeptide in Escherichia coli. With adenine-rich degenerate codons constituting the PTH-(1-5) region, intact PTH has been expressed as the only PTH product at 6.5 mg/liter. In contrast, with guanine-rich degenerate codons, the predominent product was analogue PTH-(8-84). Use of cytosine- or thymine-rich degenerate codons generated only a small amount of immunoreactive product (0.2 mg/l). With the amino terminal region reconstituted with adenine-rich degenerate codons, the mid and carboxyl regions of the synthetic gene were also reconstructed to imitate the E. coli-favored codon degeneracy. Expression yielded the intact PTH at 20 mg/liter. Gel electrophoresis and Western blots, with antibodies specific to the amino or carboxyl terminus of PTH, indicated only a single PTH-related polypeptide, with the same mobility as a synthetic intact PTH sample. Amino acid sequencing, composition analysis, mass spectrometry, and the adenylate cyclase bioassays confirmed the purified product as the processed intact PTH.

Amino Acid Sequence↗
PubMed1989

[Observations on post-traumatic osteitis].

The following study reports the frequency, the promoting factors, the therapy and her results of the 32 patients with posttraumatic osteitis we treated between 1984 and 1986 in the Surgical University Clinic Tübingen. Most of the primary injuries were caused by traffic-accidents; especially dangerous were those with motor-bikes, which led frequently via open fractures of the shank to osteitis. We saw the highest infection-rates after plate-osteosyntheses. The infects became obvious in most cases either about one month after the accident or a year later coinciding with the increased use of the limb. The most frequent bacterium was Staph. aureus both in the mono-infections and in the mixed-infections forming a third of the group. We always performed an operative therapy with the intention to stabilize the bone and to clean the infection-site. The strict performance of this management led to infect-suppression in all cases with the need of only one amputation.

Adult↗
PubMed1988

Synthesis and immunological evaluation of N-terminal, noncrossreactive tachykinin antigens.

The N-terminal hexa- or pentapeptide sequences of the three mammalian tachykinins substance P, neurokinin A, and neurokinin B have been synthesized by the conventional solid-phase procedure with 6-aminocaproyl-S-(acetamidomethyl)cysteine as a C-terminal spacer and attachment function. A fourth sequence, with an additional N-terminal 6-aminocaproyl residue on the substance P-hapten sequence, was cyclized N- to C-terminally. For this purpose, a four-level protection scheme has been applied: BOC-TFA for N-terminal protection and cleavage; TFA-stable but HF-labile anchoring function and side-chain protection; S-acetamidomethyl for semipermanent thiol protection. The side chain amino function of Lys was protected with NO2Z, stable against HF but readily cleaved with hydrogenation. The hapten sequences were coupled to maleimidated BSA, after the Acm group was removed by mercury/hydrogen sulfide treatment. Mice immunized with the three linear hapten sequences produced sera that were specific in enzyme-linked immunosorbant assay for the presented hapten and the respective tachykinin but displayed no crossreactivity at all toward the other haptens nor to one of the other tachykinins. It is concluded that this approach produced antisera, specific and selective for its respective mammalian tachykinins.

Animals↗
PubMed1986

[Results of conservative treatment of distal radius fractures].

The results of conservative treatment of fractures of the distal radius in 303 patients over a period of two years are demonstrated. 226 patients could be followed-up. The healing of the fracture was satisfactory in 78%, while the results regarding the various age groups showed considerable differences. Along with the demonstration of the functional and anatomical results in relation to age, sex, and localization the technique of fracture treatment as well as follow-up treatment are discussed.

Adolescent↗
PubMed1985

[Significance of computer tomography for operative tactics in esophageal cancer].

In patients with tumor stage T1-CT is useful in the detection of enlarged lymph nodes. In 93% of the cases with tumor stage T2-CT gives exact information about tumor extension and infiltration. In addition 70% of the patients with positive lymph nodes can be evaluated. In T3 tumor infiltration in nearby organs can be demonstrated in 94% and lymph node metastases in 79% of the cases. The therapeutic consequences are: In tumor stage T2 and T3 subtotal esophagectomy with retrosternal stomach replacement by cervical anastomosis should be aspired for reasons of postoperative irradation of the esophageal bed.

Esophageal Neoplasms↗
PubMed1985

[Acute post-traumatic cholecystitis. Caused by or following polytrauma?].

Traumatic acute cholecystitis is of secondary importance beside many other complications in the polytraumatised patient, since it is rarely diagnosed--possibly too rarely. Difficulties often arise because of a multitude of injuries, which are often life-threatening and which must be given top priority (3). Men are chiefly involved (4). In most cases, the condition is preceded by shock, but not necessarily by gallstones (10, 11). First pointers in literature were given by Mennenga (8). As early as 1939 he pointed out that blunt abdominal trauma may produce tears in the gallbladder and bile duct regions. Marre (7) described acute signs in the upper abdomen due to rupture of the bile duct. Genesis of post-traumatic acute cholecystitis is still unclarified. Apart from rupture or perforation of the gallbladder or bile ducts, it is mainly shock (4, 9, 12) which is considered to be an important causative factor.

Abdominal Injuries↗
PubMed1979

[Primary carcinoma of the extrahepatic bile ducts (author's transl)].

From 1957--1977 193 patients were treated at the surgical clinic of the University of Tübingen for carcinoma of the extrahepatic bile ducts. Gall bladder carcinoma made up 139 cases; 54 were of bile duct carcinoma. The tumors were no longer operable in two-thirds of the patients with extrahepatic bile ducts cancer. The life expectancy rate of five years for patients with gall bladder carcinoma held for 7%. Up to now only one patient with a bile duct malignancy has survived longer than five years. In the last decade essentially no improvement of median life expectancy has occurred despite improved operating techniques. Due to uncharacteristic, misleading upper abdominal symptoms, patients who suffer gall bladder or bile duct cancer are unfortunately accurately diagnosed only after the carcinoma has overcome organ borders or is already metastatic. There is reasonable hope for improved early prognosis of extrahepatic bile duct carcinoma with ERCP (Endoscopic Retrograde Cholangio-Pancreaticography) and computer-tomography. Because the possibility of a relationship between gall bladder stones and/or the chronic inflammation of gall bladder and bile ducts and the development of cancer is not out of the question, widespread prophylactic cholecystectomy and gall passage cleansing should be employed.

Adenocarcinoma↗
PubMed1979

[Intraoperative autotransfusion (author's transl)].

Intraoperative autotransfusion is an advantageous and safe method of blood replacement. In our clinic this method is established as a routine procedure in all cases with suspected massive bleeding. We used the IAT in 141 cases of surgical haemorrhage. The mean indications for IAT in surgery were emergency operations necessitated by blunt abdominal or thoracic trauma. Altogether 390 l of blood have been retransfused with an AT -- volume per patient ranging from 1 to 20 l. On an average 2,8 l per patient were transfused. Contraindications of blood replacement are tumour surgery, septic surgery, contamination by large intestinal contents and rupture of the uterus. For anticoagulation ACD-solution has been used, only in vascular surgery systemic heparinization was preferred. The main advantages of autologous intraoperative transfusion are the immediate availability of blood, the absence of the risk of hepatitis and of incompatibility reactions, reduction of pressure on the blood banks and lower transfusion costs.

Anticoagulants↗
PubMed1979

[Circular transhepatic drainage as a palliative surgical measure in central bile duct obstruction].

A transhepatic drainage tube was used in 27 patients suffering from echinococcus alveolaris of the liver of malignant process of the portal fissure from 1967 to 1978. If an hepatocholangioenterostomy is not possible, another surgical palliative procedure is necessary for drainage of the bile. The transhepatic drainage tube is a simple palliative method. The technique of this procedure, the indications, the possible complications, and the advantages are reported.

Adolescent↗
PubMed1978

[Comparative study on single layer and two layer anastomoses of small intestine (author's transl)].

The one layer anastomosis after Gambee is compared with the two layer anastomosis after Dick at the small bowel of 20 minipigs. The end-to-end anastomosis after Gambee consists of an interrupted, inverting suturing of the bowel wall. Dick suggested a closed method, applying bronchial clamps before resecting the bowel. Seromuscular sutures and inner all layer sutures are inserted interrupted. Experimental studies have been done after 4, 7, 14 and 21 days. In Histology two layer anastomoses caused delayed wound healing after 4 days. Twenty-one days after the operation histological findings in both groups were equal. Microangiographic studies showed, that in single layer anastomoses revascularization began 3 days earlier than in two layer anastomoses. Measuring of the bursting strength showed no significant differences. All parameters suggest equal value of both techniques. In our opinion the two layer anastomosis after Dick combines the advantages of a closed method with a simple, easy performable technique. We therfore apply it all over the gastrointestinal tract with exception of esophagel and rectal anastomoses.

Animals↗
PubMed1978

Experimental and clinical investigations on the transfusion of autologous blood in urological operations.

In view of the known risks in homologous blood transfusions, the procedures for transfusion of endogenous blood are gaining increasing importance. Using this fact as a basis, the feasibility of direct intraoperative autotransfusion in the area of urology was investigated. 6 mongrel dogs received blood-urine autotransfusions after cystotomy and cavotomy (n = 2) as well as after left-side nephrotomy (n = 4). Coagulation and hemolysis parameters were examined 1, 2, 24 h and 7 days after the autotransfusion, and showed transitory pathological changes which were, without exception, reversible within 7 days. Clinical effects were not observed. On the basis of favorable experience, the intraoperative, machine autotransfusion was also used clinically for renal traumas (n = 13), urinary bladder traumas (n = 4) and nephrotomies (n = 3). Postoperative checks showed pathological changes in the hemolysis and coagulation values only during the first 3 postoperative days. The blood-urine autotransfusion was well tolerated without exception. Indications and contraindications for direct intraoperative autotransfusions in the area of urological operations are discussed.

Animals↗