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Biomedical subjects

M Knauf

Publications and source records attributed to M Knauf.

At least 19 recordsLinked to original sources
PubMed2001

Pluraflavins, potent antitumor antibiotics from Saccharothrix sp. DSM 12931.

The new pluramycin-type antibiotics pluraflavin A, C43H54N2O14, pluraflavin B, C43H56N2O15, and pluraflavin E, C36H41NO14 were isolated from cultures of the Saccharothrix species DSM 12931. The structures of the novel compounds were elucidated with the aid of 2D NMR and mass spectrometric investigations. The characteristic structural element of pluraflavins A and B is an additional 4-epi-vancosamine unit at position 13 of the anthraquinone-gamma-pyrone ring system. Pluraflavin E has a carboxyl group in this position. Pluraflavin A has a reactive dimethyl epoxide side chain at position 2 of the anthraquinone-gamma-pyrone aglycon, which may explain the high activity of the antibiotic. The outstanding biological characteristic of pluraflavin A is its powerful, organ-dependent cytostatic action: the IC50 in the colon carcinoma proliferation assay is in the subnanomolar range.

Actinomycetales↗
PubMed2000

The acute effect of metformin on glucose production in the conscious dog is primarily attributable to inhibition of glycogenolysis.

Although metformin has been used worldwide to treat type 2 diabetes for several decades, its mechanism of action on glucose homeostasis remains controversial. To further assess the effect of metformin on glucose metabolism, 10 42-hour-fasted conscious dogs were studied in the absence ([Con] n = 5) and presence ([Met] n = 5) of a portal infusion of metformin (0.15 mg x kg(-1) x min(-1)) over 300 minutes. Hepatic glucose production was measured by both arteriovenous-difference and tracer methods. All dogs were maintained on a pancreatic clamp and in a euglycemic state to ensure that any changes in glucose metabolism would result directly from the effects of metformin. The arterial metformin level was 21 +/- 3 microg/mL during the test period. Net hepatic glucose output (NHGO) decreased in Met dogs from 1.9 +/- 0.2 to 0.7 +/- 0.1 mg x kg(-1) x min(-1) (P < .05). NHGO remained unchanged in Con dogs (1.7 +/- 0.3 to 1.5 +/- 0.3 mg x kg(-1)min(-1)). Tracer-determined glucose production paralleled NHGO. The net hepatic glycogenolytic rate decreased from 1.0 +/- 0.2 to -0.3 +/- 0.2 mg x kg(-1) x min(-1) (P < .05) in Met dogs, but remained unchanged in Con dogs (0.8 +/- 0.2 to 0.8 +/- 0.3 mg x kg(-1) x min(-1)). No significant change in gluconeogenic flux was found in eitherthe Metgroup (1.2 +/- 0.3 to 1.3 +/- 0.3 mg x kg(-1) x min(-1)) or the Con group (1.3 +/- 0.4 to 1.0 +/- 0.3 mg x kg(-1) x min(-1)). No significant changes were observed in glucose utilization or glucose clearance in either group. In conclusion, in the normal fasted dog, (1) the primary acute effect of metformin on glucose metabolism was an inhibition of hepatic glucose production and not a stimulation of glucose utilization; and (2) the inhibition of glucose production was attributable to a decrease in hepatic glycogenolysis and not to an alteration in gluconeogenic flux.

3-Hydroxybutyric Acid↗
PubMed2000

Kodaistatins, novel inhibitors of glucose-6-phosphate translocase T1 from Aspergillus terreus thom DSM 11247. Isolation and structural elucidation.

Two novel compounds, kodaistatin A, C35H34O11, molecular weight 630, and kodaistatin C, C35H34O12, molecular weight 646, have been isolated from cultures of Aspergillus terreus Thom DSM 11247 by solid-phase extraction, size-exclusion chromatography, and various preparative HPLC steps. The use of a range of 2D NMR measurements, in particular 13C-13C correlation measurements, has led to the clarification of the structure of kodaistatin A. Kodaistatin C is a hydroxylated derivative of kodaistatin A. Both natural products contain hydroxylated aspulvinones and identical highly substituted polyketide units. An X-ray single crystal structure analysis of aspulvinon E demonstrated the z-configuration at the central double bond. The kodaistatins are effective inhibitors of the glucose-6-phosphate translocase component of the glucose-6-phosphatase system (EC 3.1.3.9), an enzyme system which is important for the control of blood glucose levels. The IC50 is 80 nM for kodaistatin A and 130 nM for kodaistatin C.

Animals↗
PubMed1999

Feglymycin, a novel inhibitor of the replication of the human immunodeficiency virus. Fermentation, isolation and structure elucidation.

The novel peptide feglymycin has been isolated from cultures of Streptomyces sp. DSM 11171 by solid phase extraction, size exclusion chromatography and repeated reversed-phase chromatography. The molecular weight was found to be 1900.90 g/mol and the molecular formula is C95H97Nl3O30. Feglymycin contains 13 amino acids of which four are 3-hydroxyphenylglycine and five are 3,5-dihydroxyphenylglycine residues. The structure of the linear peptide has been determined by 1H and 13C NMR spectroscopy. The sequence was confirmed by the observed mass spectroscopic fragmentation pattern. As well as having weak antibacterial activity, feglymycin inhibits the replication of the human immunodeficiency virus (HIV) in vitro.

Antiviral Agents↗
PubMed1998

3874 H1 and H3, novel antifungal heptaene antibiotics produced by Streptomyces sp. HAG 003874.

New antifungal antibiotics, designated as 3874 H1 and H3, were discovered in the fermentation broth of the strain Streptomyces sp. HAG 003874. The compounds were obtained as yellow powders after sequential purification by chromatography on MCI Gel CHP20P, Fractogel HW-40 and ODS reversed phase chromatography. On the basis of the results of spectroscopic analysis, it was found that 3874 H1, C58H86N2O18, MW 1098, belongs to the p-aminoacetophenone containing family of heptaene antibiotics, while 3874 H3, C57H87NO18, MW 1073, is a non-aromatic heptaene. In addition to these, a minor component, 3874 H2, C59H88N2O18, MW 1112, a N-methyl derivative of 3874 H1 has been detected. The structures were elucidated through mass spectral analyses and 1-D and 2-D homonuclear and heteronuclear NMR data. The outstanding physico-chemical feature of 3874 H3 is its improved solubility. The new heptaenes are potent antifungal compounds with broad activity spectra, encompassing dermatophytes, yeasts and filamentous fungi.

Anti-Bacterial Agents↗
PubMed1995

The use of Zwittergent 3-14 in the purification of recombinant human interferon-beta Ser17 (Betaseron).

A new method for purifying human interferon-beta SER17 from E. coli-derived inclusion bodies has been developed. This procedure eliminates the need for strong denaturants, such as sodium dodecyl sulfate or chaotropes. The procedure makes use of a nondenaturing detergent and a brief incubation at pH 12 to solubilize interferon-beta Ser17 from inclusion bodies. The detergent used was Zwittergent 3-14 (nonionic and pH-insensitive), which is included in the class of sulfobetaines (RN+ (CH3)2(CH2)xSO3-). Zwittergent 3-14 was used in combination with urea to produce a urea/Zwittergent 3-14 washed inclusion body preparation enriched in human interferon-beta Ser17 (Betaseron). Solubilization of inclusion bodies was accomplished by employing a brief (1 minute) shift to pH 12 in the presence of 2.5% Zwittergent 3-14 followed by rapid adjustment to pH 8.0. Solubilization was complete, and the solution could be rapidly adjusted to pH 8 without any observable precipitation of protein. The resultant supernatant could be successfully subjected to a number of chromatographic and analytic procedures, many of which are not compatible with strong anionic detergents, such as SDS. Betaseron was purified from Zwittergent 3-14 solubilized inclusion body lysates using both ion-exchange and size-exclusion chromatography. Purified Betaseron retained bioactivity and could be refolded by simple dialysis against a nonreducing buffer. This method represents a novel procedure for purifying Betaseron from inclusion bodies using a nondenaturing detergent and ion-exchange chromatography.

Detergents↗
PubMed1993

[Principles of muscle efficiency in weightlessness].

Depending on the time spent in a space station, weightlessness causes varying changes to various organs and regulatory mechanisms of the human organism, among them the structures of the active and passive locomotor system. Experience has shown that regular physical activity using varying forms of training is necessary to keep astronauts and cosmonauts healthy, efficient and fit for work and to prepare them for a safe return to terrestrial conditions. One of the main tasks of physical activity is therefore to counteract the changes in the neuromuscular function, muscle strength, endurance and fatigability under conditions of weightlessness. So far, the diagnostics of these changes was limited to dynamometric measurements before and after space flights as no dynamometric method had been devised which was precise enough under conditions of weightlessness. The development and the introduction of the dynamoergometer Motomir is described against the background of previous results obtained by dynamometric, ergometric, morphometric, biochemical, histochemical and neuromuscular examinations before and after missions of varying duration under conditions of weightlessness. This device was used for the first valid and reproducible examinations of muscle strength and endurance aboard the space station Mir during the Austro-Russian space mission Austromir. The results of the examinations with this speed-controlled dynamometer and training device obtained during a short-term flight of 10 days and a long-term flight of 6 months are described and compared to previous results in the literature. Based on the existing training devices, training methods and training plans and the results of the Motomir Study, plans for devices and methodologies for future long-term space flights of up to 3 years' duration will be discussed. Finally, the possible use of a speed-controlled dynamometer and training device for rehabilitation on earth after injuries, surgery and immobilization of the active and passive locomotor system as well as in the bed-rest syndrome is being presented.

Animals↗
PubMed1991

[Biomechanical effects of intra-articular ankle bone fractures on the ankle joint. An experimental study].

Intraarticular heelbone fractures lead to cartilage damage by way of joint surface incongruence. This causes arthrosis of the lower ankle joint. The influence of a dislocated calcaneus fracture on the upper ankle joint was documented in an experimental study on eight cadaver legs. We performed an osteotomy of the calcaneus to imitate a typical fracture, placed a pressure film into the upper ankle joint and subjected the joint to axial pressure of 850 N. Changes in contact area and pressure pattern were measured in different flexion/extension positions of the foot. Results with respect to total contact area and high-pressure contact zone are discussed.

Ankle Joint↗
PubMed1990

[Fatigue fracture of the tibia following osteosynthesis. An interesting case].

Stress-fractures most often affect healthy bones, in the majority of cases the tibia. We report a case of a young man who had a stress-fracture 18 months after osteosynthesis of a lower leg-fracture. Under biomechanical aspects an oscillation-fracture is mostly probable because the angle of the fracture is exactly 45 degrees to the longitudinal axis of the tibia.

Adult↗
PubMed1990

[Primary and secondary soft tissue injuries of the hand and therapeutic possibilities].

Primary treatment of soft tissue hand injuries is most important for further management and progress. It ensures best protection of lower structures. Soft tissue lesions that can not be closed without resulting tensions need instant plastic-surgical therapy. Various possibilities that range from split skin flaps to distant flaps with microvascular anastomosis can be chosen to cover primary as well as secondary soft tissue defects.

Hand Injuries↗
PubMed1988

[Surgical treatment of chronic ligament injuries of the knee joint].

Treatment for median knee-joint instability with a case history long time back may occasionally be time-consuming and dissatisfactory to patient and doctor. Several synthetic materials and autologous grafts are used in surgical therapy. Some of the methods are described in this paper. In one of them use of autologous tissue is combined with its "dynamisation".

Chronic Disease↗
PubMed1986

[Surgical indications in struma nodules].

From 1980 to 1985 1,839 patients with thyroid nodules were investigated. 98% of them showed ultrasonic patterns of either echo-poor or complex structures, 85% of the nodules were scintigraphically cold, in 10% (n = 182) cytological findings were positive or at least suspect. Of these 182 patients 60 underwent operation, whereas 122 were followed up continuously. In 35 of 60 patients operated histological examination confirmed thyroid carcinomas. The combination of echo-poor, cold nodules and cytological positive or suspect findings urgently requires operation.

Diagnosis, Differential↗
PubMed1982

[Palliative treatment of inoperable tumors of the efferent bile ducts].

Our method of percutaneous transhepatic cholangiodrainage (PTCD) and radiotherapy shows better results and prognosis in patients with inoperable tumors of the liver, biliary system and pancreas. PTCD was performed in patients with progressive obstructive jaundice due to inoperable tumors to decompress the hepatobiliary system and to reduce jaundice. This was combined with radiotherapy which was performed pre- and postoperatively and without operation. Aim of radiotherapy was to reduce the tumor and also to explore the possibility of radical operation. Radiotherapy was carried out in most patients with Linear accelerator (Linac), and in some with Betatron or Telecobalt 60. In a few cases was chosen: 1) two phase radiotherapy 2) and/or a combination of ray therapies. Inoperable tumors, which can not be excised, should be treated intraoperatively with radiation therapy. Only after a radiation with 3000-4000 rad linac, tumors showed shrinkage in size and at the same microscopic degenerative changes in tumor cells were observed.

Adenocarcinoma↗