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G Günther

Publications and source records attributed to G Günther.

At least 37 records · Page 2Linked to original sources
PubMed1996

Computer-aided modeling of structure stabilizing disulfide bonds in recombinant human interferon-gamma.

We present a general search algorithm for possible insertion sites of disulfide bonds in proteins based on the coordinates of the solved X-ray or NMR structure, allowing the insertion of disulfide bonds with a minimum of conformational tension and backbone rearrangements. The FORTRAN 77 program "Ssuitable' was written for this purpose. This methodological approach was applied to recombinant human interferon-gamma (rhu-IFN-gamma), a cytokine of great pharmaceutical interest with a wide variety of biological activities including antiviral, antiproliferative and immunomodulatory effects. A model based on the C alpha-coordinates obtained from the Brookhaven data base was built. Four different insertion sites were selected in the model, connecting the two subunits of the homodimer. The thermodynamic stability of rhu-IFN-gamma is low, limiting its clinical application. We expect that the insertion of additional new disulfide bonds will enhance the thermodynamic stability as well as protect the protein against proteolytic degradation.

Amino Acid Sequence↗
PubMed1996

Imipenem/cilastatin monotherapy as salvage treatment in febrile neutropenic patients.

Imipenem/cilastatin (I/C) monotherapy was used as salvage treatment in 55 neutropenic patients (58 fever episodes) after treatment failure on first-line antibiotic therapy. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiologic evidence of infection on I/C monotherapy alone. Twenty-five out of the 58 episodes (43%) were classified as success, 6 episodes (10%) as initial response but the regimen had to be modified (amphotericin B was added) and 27 episodes (47%) as failures. In episodes with documented infections 9 out of 23 (39%) were classified as success. All patients survived during the first 72 hours after change to I/C therapy. One patient had to discontinue I/C due to a skin rash. In conclusion, the use of a treatment algorithm with I/C monotherapy as second-line treatment was safe and effective. Other antimicrobial agents, most often vancomycin and/or amphotericin B, had to be added in half of the patients.

Adolescent↗
PubMed1996

Trimethoprim-sulfamethoxazole plus amikacin versus ceftazidime monotherapy as empirical treatment in patients with neutropenia and fever.

In a prospective randomized comparison, 217 episodes of fever (oral temperature > 38.5 degrees C on 1, or 38.0 degrees C on 2 occasions with a minimum interval of 4 h between recordings) during neutropenia (neutrophil count < 0.5 x 10(9)/I), patients were empirically treated with trimethoprim-sulfamethoxazole plus amikacin (TMP/SMZ plus AMI) or ceftazidime. Successful antibiotic treatment was defined as eradication of all signs, symptoms and microbiological evidence of infection on the primary therapy alone. The overall success rate did not differ between the 2 treatment groups: 31/102 (30%; 21-39%, 95% confidence interval, CI) for TMP/SMZ plus AMI and 41/115 (36%; 27-44%) for ceftazidime (difference 0.06 +/- 0.13, 95% CI). The corresponding numbers for documented infections were 12/50 (24%; 12-36%) and 14/60 (23%; 12-35%), respectively (difference 0.01 +/- 0.16). One patient in the TMP/SMZ plus AMI group and 2 patients in the ceftazidime group died from Gram-negative bacteraemias within 72 h. No other early deaths were observed. Antibiotics were changed due to adverse events in 2 episodes of each treatment group. In conclusion, this study demonstrates that TMP/SMZ plus AMI combination is comparable (i.e. a difference of < 20%) to ceftazidime monotherapy with regard to efficacy and safety in haematological patients with severe neutropenia. Both regimens require frequent modifications, particularly in bacteraemic fever episodes. However, in centres with a low frequency of isolation of Pseudomonas and especially of multi-resistent Pseudomonas strains, TMP/SMZ plus AMI offers an inexpensive alternative for the empirical treatment of febrile neutropenia.

Adolescent↗
PubMed1996

Intrathecal production of neopterin and beta 2 microglobulin in tick-borne encephalitis (TBE) compared to meningoencephalitis of other etiology.

To study the pathophysiology of tick-borne encephalitis (TBE), the kinetics of neopterin and beta 2 microglobulin (beta 2M) production were measured in sequential, cerebrospinal fluid (CSF) and serum samples in 133 patients with aseptic meningoencephalitis (TBE, n = 72; non-TBE, n = 61). Intrathecal production of neopterin was demonstrable in all patients. Neopterin levels in CSF were elevated already at day 2: geometric mean value in TBE 36 nmol/l (range 1-253), in the non-TBE group 29 nmol/l (0.2-96). At day 9 and week 6 the neopterin level was significantly higher in TBE (86 (19-725) and 17 (4-122) nmol/l) than in non-TBE (28 (5-109) and 3 (0.2-58) nmol/l) (p < 0.001). After 1 year CSF levels were within the normal range. The beta 2M response in CSF followed the pattern of neopterin. The intensity and duration of neopterin and beta 2M was not correlated to the clinical course. Neopterin seems to be a more sensitive indicator of intrathecal T-cell response and inflammatory reaction than beta 2M. The results indicate that a long-lasting strong inflammatory reaction is of pathophysiological significance in TBE.

Adolescent↗
PubMed1995

Endotoxaemia and inflammatory mediators in febrile patients with haematological disease.

OBJECTIVES: To study the pattern of plasma levels of endotoxin, tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and C-reactive protein (CRP) in febrile neutropenic patients and to assess the potential diagnostic value of these analyses. DESIGN: Consecutive prospective study. SETTING: Patients treated at the haematology ward at Danderyd Hospital, Sweden. SUBJECTS: Ninety-four patients with fever and haematological disease entered the study (male/female: 59/35) with 176 febrile episodes. INTERVENTIONS: Blood samples were drawn at days 0, 1, 2 and 6 after onset of fever for analysis of, endotoxin, TNF-alpha, IL-6 and CRP. RESULTS: Infectious aetiology was established in 62.5% of the febrile episodes. Blood cultures showed significant growth in 71/176 (40.3%) febrile episodes. Nonbacteraemic bacterial infections were diagnosed in 34/176 (19.3%) episodes. Endotoxin was detected in plasma in 40% of febrile episodes regardless of aetiology. TNF-alpha was detected in 61% and IL-6 in 94% of all febrile episodes. The initial TNF-alpha and IL-6 levels were significantly higher in patients with Gram-negative bacteraemia than in patients with other causes of fever (P < 0.001). In episodes evaluated as successful after empirical antibiotic treatment, a significant (P < 0.001) decrease in CRP concentrations were found on day 6 after onset of fever. CONCLUSIONS: The sustained, low-grade endotoxaemia and persistently elevated levels of TNF-alpha and IL-6 found in febrile patients may reflect a failing mucosal barrier that allows endogenous bacterial products to reach the circulation. The diagnostic value of endotoxin, TNF-alpha, IL-6 and CRP to discriminate between bacteraemic and nonbacteraemic febrile episodes was very limited. The study supports the present policy of broad, empirical antibiotic treatment in patients with haematological disease and fever.

Adolescent↗
PubMed1993

Detecting localized proton currents in photophosphorylation by procaine inhibition of the transthylakoid pH-gradient.

The relationship between the transthylakoid pH-gradient, delta pH, and the velocity of photophosphorylation, Vp, in thylakoid membranes from spinach was investigated using the local anesthetic amine procaine as inhibitor of delta pH. When delta pH was driven by Photosystem (PS) II+I-dependent electron flow, passing through the cytochrome b6/f complex, inhibition by procaine was accompanied by an increase of ATP formation. It appeared that procaine allowed for values of Vp similar to those in controls (without procaine) at a significantly lower delta pH than in the controls. In contrast, when delta pH was driven by cyclic electron flow around PS I or by PS-II+I-dependent electron flow via a bypass around the cytochrome b6/f complex, or by PS II alone, procaine simultaneously caused an inhibition of delta pH and a decrease of ATP formation. Inhibition of delta pH by procaine did not induce an electrical membrane potential gradient that otherwise may have energetically compensated for the observed decline of delta pH. The electron flow capacity was unaffected by procaine. However, inhibition of delta pH did not significantly relax pH-dependent control of electron flux. Procaine accelerated ATP hydrolysis by pre-activated thylakoid ATPase to rates which were observed in the presence of uncouplers and had no direct effect on the activation state of the ATPase. The shift in the relationship between delta pH and Vp towards lower delta pH persisted in thermodynamic equilibrium between the phosphorylation potential and delta pH. The data indicated that the unconventional effect of procaine on photophosphorylation may be related to effects on proton translocation at the cytochrome b6/f complex and that a localized protonic coupling may occur between cytochrome b6/f and thylakoid-ATP-synthase complexes.

Chloroplasts↗
PubMed1993

[Interferon. An overview of the state of basic research with special regard to interferon-gamma].

Interferons / An overview on the state of basic research with special regard to interferon-gamma Interferons are multifunctional glycoproteins with a broad range of antiviral, antiproliferative and immunoregulatory effects on the target cell. This review deals with the basics as well as with more recent developments in interferon research. A historic overview of 35 years of interferon research since the discovery of interferons by Isaacs and Lindenmann in 1957 introduces the most important milestones in this field and appreciates the work of the participating researchers. A brief description of the classification of interferons based on different tissue sources, different antigenic properties and different induction behaviour is made. The main part of this review focuses on human interferon-gamma. We discuss recent work on the structure-function relationship of interferon-gamma. The interferon-gamma receptor and its role in signal transduction is another part of this paper. The structure and length of the C-terminal region of interferon-gamma seems to be important for receptor binding and expression of biological activities. A conservative estimate is that the family of IFN-activated genes numbers 15-20 in most cells.

Animals↗
PubMed1991

Septicemia in patients with hematological disorders and neutropenia. A retrospective study of causative agents and their resistance profile.

In order to identify the cause of septicemia and the resistance patterns of bacteria in Swedish patients with hematological disorders, all positive blood cultures collected at a hematological ward during 1980-1986 were evaluated retrospectively. 198 episodes of septicemia in 129 patients were recorded. 54% were males and 46% women with a median age of 67 years (range 16-88). Patients with acute leukemia (46%), lymphoma (19%) and myeloma (19%) dominated. The absolute neutrophil count (ANC) was less than 0.5 x 10(9)/l in 76% of the bacteremic episodes. A total of 253 consecutive isolates were found with 53% Gram-negatives and 47% Gram-positives. The dominating pathogens were Escherichia coli (27%), klebsiella/enterobacter (15%), pseudomonas (7%), coagulase negative staphylococci (13%), alpha-streptococci (13%), Staphylococcus aureus (10%) and anaerobes (6%). Coagulase negative staphylococci showed a significant increase in isolation rate during the study period. The majority of E. coli were resistant to ampicillin. The susceptibility of klebsiella/enterobacter to ceftazidime and cefuroxime was reduced, while no imipenem resistant strains occurred. Among coagulase negative staphylococci 61% were resistant to isoxazolylpenicillin, none to vancomycin. No dramatic changes in the etiology of septicemia or the susceptibility pattern during the study period were noticed. Coagulase negative staphylococci, S. epidermidis in particular, constitute an increasing problem among granulocytopenic patients.

Acute Disease↗
PubMed1988

[Not Available].

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History, Modern 1601-↗
PubMed1979

[Catamnestic studies of normally intelligent encephalopathy patients among children and adults].

Our studies show that the special features in the psychic development of encephalopaths showing normal intelligence consist in delayed motor, intellectual and educational progress. While motor retardation is reduced with age, as a result of such factors as rhythmical and psychomotor musico-therapy, individual intelligence test results drop more frequently at school age. The drop is less marked in students attending special classes, although they go back to their original schools after grade 4. The trend toward deterioration in intellectual development is reduced with age, i.e. when educational progress as encouraged by society, slows down. Despite their normal performance with regard to intelligence these students markedly lag behind their healthy contemporaries as far as performance at school is concerned.

Adolescent↗