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Biomedical subjects

H Bender

Publications and source records attributed to H Bender.

At least 109 records · Page 6Linked to original sources
PubMed1977

[Cyclodextrin glucanotransferase from Klebsiella pneumoniae. 1. Formation, purification and properties of the enzyme from Klebsiella pneumoniae M 5 al (author's transl)].

1. The strain M 5 al of Klebsiella pneumoniae grows excellently with starches. We were able to show that besides the pullulanase associated with the external membrane of the cells the bacterium produces an inducible, extracellular cyclodextrin glucanotransferase [1,4-alpha-D-glucan-4-alpha-(1,4-alpha-glucano)-transferase (cyclising) (EC 2.4.1.19)]. Potato starch and cyclohexaamylose or cycloheptaamylose were found to be the best "inducing" carbon sources for the synthesis of the enzyme. When the bacteria are grown batchwise, maltose is a poorly "inducing" carbon source; larger quantities of the enzyme are synthesized by continuous cultivation with maltose as growth limiting factor. 2. For the determination of the cyclodextrin glucanotransferase-activity an assay method wsa worked out. 3. The enzyme could be separated from the culture filtrate and purified to more than 90% in few steps. At a total yield of 61.2% related to the activity of the culture filtrate employed we received an enzyme solution with the specific activity of 26.6 units/mg protein. Some properties of the enzyme are described. 4. The products formed from amylopectin by the enzyme were analyzed. Somewhat more than half the amylopectin was found as cyclodextrins. 29.3% of the cyclodextrin fraction were cycloheptaamylose, 47.2% cyclohexaamylose and 10.7% exo-branched cyclohexaamylose. 12.8% of cyclohexaamylose were obtained from a cyclodextrin glucanotransferase-limit dextrin after debranching by pullulanase and exposing the product to the action of the glucanotransferase again. 5. The importance of the cyclodextrin glucanotransferase for the utilization of starches by this strain of Klebsiella pneumoniae is discussed. After a first characterization the enzyme is compared to the amylase of Bacillus macerans.

Amylopectin↗
PubMed1977

Hypoplasia of the left ventricle: rare cause of postoperative mortality in tetralogy of Fallot.

Severe left ventricular hypoplasia in tetralogy of Fallot is a rare complication. A case history of a 3 year old child who died after attempted repair of tetralogy is presented. Left ventricular end-diastolic volume was 26 ml/m2 (only 45 percent of predicted normal) after repair with normal filling pressure and no evidence of tamponade. Clinical examination, chest X-ray film, electrocardiogram and qualitative assessment of a preoperative left ventriculogram were not useful in assessing this degree of left ventricular hypoplasia; quantitative determination of left ventricular volumes is required for this purpose. When left ventricular end-diastolic volume is less than 55 percent of predicted normal, a shunt procedure may be indicated as an initial procedure with subsequent repair 1 to 2 years later, after left ventricular enlargement.

Child, Preschool↗
PubMed1976

1, 4-alpha-Glucan phosphorylase from Klebsiella pneumoniae purification, subunit structure and amino acid composition.

1. A 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae has been purified about 80-fold with an over-all yield greater than 35%. The purified enzyme has been shown to be homogeneous by gel electrophoresis at different pH-values, by isoelectric focusing, by dodecylsulfate electrophoresis and by ultracentrifugation. 2. The molecular weight of the native enzyme has been determined to be 180 000 by ultra-centrifugation studies, in good agreement with the value of 189 000 estimated by gel permeation chromatography. 3. The enzyme dissociates in the presence of 0.1% dodecylsulfate or 5 M guanidine hydrochloride into polypeptide chains. The molecular weight of these polypeptide chains has been found to be 88 000 by dodecylsulfate polyacrylamide gel electrophoresis and 99 000 by sedimentation equilibrium studies, indicating that the native enzyme is composed of two polypeptide chains. 4. The enzyme contains pyridoxalphosphate with a stoichiometry of two moles per 180 000 g protein, confirming that the 1,4-alpha-glucan phosphorylase from Klebsiella pneumoniae is a dimeric enzyme. 5. The amino acid composition of the enzyme has been determined, and its correspondence to that of 1,4-alpha-glucan phosphorylases from other sources is discussed. 6. The pI of the enzyme has been shown to be 5.3 and its pH-optimum to be about pH 5.9. The enzyme is stable in the range from pH 5.9 to 10.5.

Amino Acids↗
PubMed1976

Possible evolutionary relationships of the nitrogenase proteins.

Comparisons of the amino acid compositions of the nitrogenase proteins from different organisms and their correlation with cross-reactivities and taxonomical data suggest an evolution within bacterial genomes rather than within plasmids. Comparisons of the amino acid compositions of nitrogenases and other ATP-ases show similarities which might be due to the evolution of these ATP-ases from a common ancestral protein.

Adenosine Triphosphatases↗
PubMedDate not supplied

Effect of vasoactive intestinal peptide, peptide histidine isoleucine and growth hormone-releasing factor-40 on bombesin-like immunoreactivity, somatostatin and gastrin release from the perfused rat stomach.

Bombesin-like immunoreactivity (BLI) has been demonstrated in neurons of the gastrointestinal tract and gastric BLI secretion can be demonstrated in response to the classical neurotransmitter acetylcholine. Since structurally related peptides VIP, PHI and GRF have to be considered as peptidergic neurotransmitters it was of interest to determine their effect on gastric BLI secretion. Additionally, somatostatin (SLI) and gastrin secretion was examined. The isolated stomach of overnight fasted rats was perfused with Krebs-Ringer buffer via the celiac artery and the effluent was collected via the portal vein. The gastric lumen was perfused with isotonic saline at pH7 or pH2. All four peptides were tested at a dose of 10(-11) M and 10(-8) M at both pH levels and in addition the effect of VIP and PHI was examined at 10(-14) M and 10(-12) M during luminal pH2. At luminal pH7 VIP and PHI stimulated SLI release at 10(-8) M but had no effect on BLI or gastrin secretion. rGRF and hpGRF were both ineffective on SLI and gastrin release while rGRF inhibited and hpGRF stimulated BLI secretion. This effect was not dose related. At luminal pH2 all four peptides stimulated BLI secretion. Stimulation by PHI was already observed at a dose of 10(-14) M while VIP elicited a stimulatory effect at 10(-12) M. PHI at the two lowest concentrations of 10(-14) and 10(-12) M elicited a stimulation of SLI and gastrin release while the same doses of VIP and the higher doses of all four peptides had no effect on SLI and gastrin secretion at an acidic intraluminal pH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Possible role of FDG-PET in the evaluation of urologic malignancies.

Positron-emission tomography (PET) employing 18F-labeled deoxyglucose (FDG) has been found to be a highly sensitive and rather specific tool in the detection of a variety of malignant carcinomas. Due to high resolution and outstanding image quality its complementary and supplementary role as compared to morphological methods has increasingly been acknowledged. Urinary-tract malignancies, with the exception of prostate carcinoma, have a rather low incidence and thus experience with FDG-PET is limited. We have compared the diagnostic accuracy of FDG-PET mainly in the primary staging of malignant testicular carcinoma, prostate and renal cell carcinoma. Our data indicate, that FDG-PET is more accurate in the detection of lymph node metastases in malignant testicular cancer as compared to CT, but also fails to detect micrometastases and highly differentiated teratoma. Its role in prostate carcinoma is questionable due to the low metabolic activity of this type of cancer. In all other urinary tract malignancies no final conclusions can be drawn, due to limited experience.

Carcinoma, Renal Cell↗
PubMedDate not supplied

Value of 18fluoro-deoxyglucose positron emission tomography in the staging of recurrent breast carcinoma.

The aim of the study was to evaluate the feasibility of staging recurrent breast carcinoma employing fluorine-18-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) under routine clinical conditions. In 75 patients with suspected recurrent or metastatic disease, whole-body FDG-PET was performed and results correlated with morphological imaging (CT/MRI) data and verified by histological findings. FDG-PET correctly identified 16 patients with local recurrence, 28 with lymph node involvement, 15 with bone, 5 with lung and 2 with liver metastases. CT/MRI identified 10 patients with local recurrences, 17 with lymph node involvement, 6 with bone, 5 with lung and 1 with liver metastases. FDG-PET detected 6 local recurrences, 8 lymph node, and 7 bone metastases, which were not visualized by CT/MRI. Our data provide the basis for use of FDG-PET in the whole-body restaging of recurrent breast carcinoma in preselected patients under routine clinical conditions.

Adult↗
PubMedDate not supplied

Clinical aspects of local and regional tumor therapy with 188Re-RC-160.

Somatostatin-receptors have been found to be overexpressed in a variety of neuro-endocrine and epithelial cancers. While the introduction of a long-acting somatostatin-analogue, octreotide, exerted mainly anti-cancer activity in neuro-endocrine tumors, no convincing results have been demonstrated in other cancers. RC-160, another somatostatin-analogue has been selected because of its high receptor affinity and its anti-cancer activity. 188Re is a generator produced radionuclide with favourable gamma and beta-emission, allowing diagnostic and therapeutic application. The results of in vivo biodistribution and therapeutic outcome following systemic, intralesional and intracavitary application in animal studies employing 188Re-RC-160 are summarized. Safety considerations, dosimetry estimates and applicable indications are outlined. The clinical impacts of this radiopharmaceutical in cancer management are discussed.

Animals↗
PubMedDate not supplied

Availability of rhenium-188 from the alumina-based tungsten-188/rhenium-188 generator for preparation of rhenium-188-labeled radiopharmaceuticals for cancer treatment.

Rhenium-188 (beta- = 2.2 MeV; gamma = 155 keV; T1/2 16.9 hours) is an attractive therapeutic radioisotope which is produced from decay of the reactor-produced tungsten-188 parent (T1/2 69 days) and thus conveniently obtained on demand by elution from the alumina-based tungsten-188 /rhenium-188 generator system. The rhenium-188 is obtained as sodium perrhenate by elution of the generator with 0.9% saline. The post elution use of disposable tandem, ion-exchange columns is a simple method for the concentration of rhenium-188 saline solutions with specific volumes > 500 mCi/ml. This method can also extend the useful shelf-life of the generator, which can be as long as one year. The long useful shelf-life of the generator is expected to provide rhenium-188 at very reasonable costs for routine preparation of a variety of radiopharmaceuticals for the treatment of a variety of cancers including breast cancer. We are evaluating two types of Re-188-labeled agents under investigation which have potential for the treatment of breast cancer. Rhenium-188-labeled hydroxyethylidenediphosphonate (HEDP) and Re-188-dimercaptosuccinic acid (DMSA) are being applied for palliative treatment of pain associated with skeletal metastases, and the Re-188-RC-160 somatostatin analogue [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Lys-Val-Cys-Trp-NH2] for somatostatin-receptor-positive tumors. The results of initial clinical studies with the two bone pain agents demonstrate good targeting to skeletal metastases, and use of Re-188-HEDP has resulted in pain palliation with minimal bone marrow suppression in the initial patient studies. While these initial studies have been conducted in patients with prostate cancer, similar results are expected in planned studies in breast cancer patients. In animal studies, Re-188-RC-160 has been successfully used for the local/regional treatment of experimental breast cancer and other cancers. Re-188-RC-160 binds to somatostatin-receptor-positive cells both in vitro and in vivo, including breast cancer cells (ZR-75-1 breast carcinoma and NCI-H69 human small cell ling carcinoma), but not to binding-negative cells (Raji, Burkitt's lymphoma). A structurally similar Re-188-cyclic peptide with different binding specificity (CTOP [cyclic NH2-(D)-Phe-Cys-Try-(D)-Trp-Orn-Thr-Pen-Thr-ol]; an opiate-receptor antagonist) did not bind to target cells. Both gentisic acid and ascorbic acid are present in the Re-188-HEDP and Re-188-RC-160 formulations, and have been found to also significantly reduce radiolytic degradation of the somatostatin peptide analogues, and may have general application in the stabilization of Re-188-labeled radio-pharmaceuticals.

Aluminum Oxide↗
PubMedDate not supplied

External beam radiation enhances antibody mediated radiocytotoxicity in human glioma cells in vitro.

Enhanced accumulation of monoclonal antibodies in tumor tissue has been observed as a result of external beam irradiation (EBR). This effect was mainly attributed to increased vascular leakage due to unspecific radiation damage of vascular endothelial cells. The aim of this study was to investigate the effects of EBR on expression and antibody-binding of epidermal growth-factor receptor (EGF-R) in human glioma cells in-vitro. High-grade glioma cells were irradiated with conventional x-rays (0-3600 Rad) and surface binding, internalization and radiocytotoxicity of 125I-labeled monoclonal antibody (MAb) 425, specific for human EGF-R, was tested. EBR showed a short-term dose and time dependent increase of specific MAb 425 binding and internalization in receptor positive cell lines U87-MG and A1207. This effect was probably due to a mitotic block and an increase in cellular volume. Combination of EBR and 125I-425 showed additive effects on cell vitality/survival and was more pronounced in contact inhibited cells as compared to cells growing in a log-phase. We assume that cells exposed to 125I-labeled MAb 425 are only able to accumulate a critical number of DNA double-strand breaks when the doubling-time is prolonged e.g. under contact-inhibition or radiation induced mitotic blockade. We conclude that EBR has no negative effects on EGF-R expression, MAb-binding and internalization. The combination of EBR and 125I-MAb 425 enhances cytotoxic efficacy and thus supports adjuvant use in the clinical management of high-grade glioma.

Animals↗
PubMedDate not supplied

Pre-clinical experience with Re-188-RC-160, a radiolabeled somatostatin analog for use in peptide-targeted radiotherapy.

The clinical potential of radiolabeled peptides such as octreotide and VIP has been widely established for tumor localization. Radiotherapy based on the tumor binding potential of the peptides and the radiotoxic effects of beta- or a-emitting radionuclides is an extension of such applications. Rhenium-188 (T1/2 16.9 hr, beta-max 2.1 MeV) coupled to the analogue RC-160 has been used to establish the feasibility of treating tumors with radiolabeled peptides, and our experience with this approach is summarized. In three different experimental tumor models (human prostate, mammary gland, and small cell lung carcinomas) in nude mice, treatment resulted in significant reduction or elimination of tumor burden. Two routes of administration were used: intra-lesional injection (prostate carcinoma) and intra-cavity injection (mammary and SCLC). Re-188-labeled negative control peptides bound to tumor cells to a low extent and did not exhibit therapeutic benefit. RC-160 by itself did not result in therapeutic benefit. Tumors which did not bind Re-188-RC-160 did not evidence a therapeutic benefit. Uncoupled Re-188 (control) was rapidly excreted via the urinary bladder and did not accumulate in either tumors or normal tissues even following direct injection. Instant radiolabeling kits containing 200 micrograms of RC-160 were labeled with < 3000 MBq of Re-188 in 30 minutes with no need for subsequent purification. These studies establish the conceptual feasibility of targeted radiotherapy based on the local or regional administration of radiolabeled peptides.

Animals↗