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Biomedical subjects

C Huber

Publications and source records attributed to C Huber.

At least 235 records · Page 13Linked to original sources
PubMed1991

Immunotherapy with monoclonal anti-idiotypic antibodies: tumour reduction and lymphokine production.

A patient with a B-cell chronic lymphocytic leukaemia was treated with a murine IgG1 monoclonal anti-idiotypic antibody (MoAb anti-id). After a total of 773.2 mg MoAb anti-id had been administered with a maximum daily dose of 83.2 mg, 90% tumour reduction was established within 2 weeks. Although in vitro the tumour cells were stimulated by MoAb anti-id no signs of tumour cell activation were observed in vivo during therapy with MoAb anti-id. The rapid tumour reduction suggests that the proliferation-enhancing property of anti-id is not a contra-indication for immunotherapy. The FcR II receptors on the patients monocytes could interact with the IgG1 monoclonal used. MoAb anti-id administration induced strongly decreased platelet counts, dependent on the amount of serum idiotype that had to be cleared. Antibody administration activated the macrophage/monocyte system, reflected in the neopterin profile, resulting in TNF alpha production and simultaneously strong reductions of circulating tumour cells. The partial remission lasted 3 months, then the tumour reappeared. These data show that a straightforward therapy with MoAb anti-id, in itself, has a strong potential, but is not sufficient to eradicate the tumour permanently. Further study will be needed to improve the clinical results with this kind of therapy.

Aged↗
PubMed1991

Recombinant tumour necrosis factor alpha administered subcutaneously or intramuscularly for treatment of advanced malignant disease: a phase I trial.

The pharmacokinetics, toxicity and biological effects of subcutaneous and intramuscular treatment of cancer patients with recombinant tumour necrosis factor alpha (rTNF-alpha) was investigated. 17 patients suffering from refractory malignant disease were treated with either 1.0 micrograms/m2, 10 micrograms/m2 or 100 micrograms/m2 rTNF-alpha. Vital signs, peripheral blood cell counts, TNF and interferon (IFN) gamma serum levels, neopterin, beta 2-microglobulin, C reactive protein (CRP) and cortisol levels were measured immediately before and 2, 12, 24, 48 and 168 h after the first administration of rTNF-alpha. Tumour response was evaluated after 4 and 12 weeks of treatment. The pharmacokinetics followed the same characteristics as those reported for other cytokines. Major toxicities were dose dependent and comprised fever, constitutional symptoms and hypotension. TNF dependent changes were observed in serum levels of IFN-alpha, CRP, neopterin, beta 2-microglobulin, cortisol and white blood cell counts. No objective tumour response was observed. This study indicated that rTNF-alpha administered subcutaneously or intramuscularly results in measurable TNF serum levels, significant toxicity and biological response in absence of clinical efficacy in patients with advanced cancer.

Adult↗
PubMed1991

Enhanced serum levels of soluble HLA class I molecules are induced by treatment with recombinant interferon-gamma (IFN-gamma).

In order to investigate serum levels of soluble HLA class I antigens after single injection of various doses of recombinant IFN-gamma (rIFN-gamma) and to correlate the changes observed to beta-2-microglobulin serum levels, we studied five patients with metastasizing renal cell carcinoma. Each patient received three treatment cycles of 10, 100 and 500 micrograms rIFN-gamma three times at weekly intervals. The treatment cycles were separated by a therapy-free interval of 2 weeks. The order of dose levels was randomly assigned to each patient. Serum levels of soluble HLA class I proteins were measured by an ELISA in samples drawn immediately before and 4, 24, 48, 72 and 168 h after each administration of rIFN-gamma. Beta-2-microglobulin was assessed in parallel using a commercially available radioimmunoassay. Significant induction of soluble HLA class I protein serum levels was observed after treatment with 100 and 500 micrograms rIFN-gamma. The increments peaked after 2-4 days and remained elevated for up to more than 7 days. A significant correlation between increments of soluble HLA class I proteins and beta-2-microglobulin was observed. We conclude that measurement of soluble HLA serum levels is practical for monitoring induction of HLA class I synthesis in patients treated with rIFN-gamma. The correlation observed between induction of beta-2-microglobulin and soluble HLA class I proteins indicates that measurement of beta-2-microglobulin might be sufficient for the biological response monitoring in clinical studies.

Carcinoma, Renal Cell↗
PubMed1991

Cachexia and tumour necrosis factor-alpha in cytomegalovirus infection.

Although cachexia is a common feature of cytomegalovirus infection, little is known about its cause. To explore any contributory role that tumour necrosis factor-alpha (TNF) might have the serum concentrations of TNF in eight patients who developed CMV disease after liver transplantation were investigated. All patients exhibited pronounced and long lasting increases in TNF serum concentrations. Increased endogenous TNF concentrations were associated with weight loss and anorexia. In contrast, liver transplant recipients without CMV disease showed no weight loss.

Cachexia↗
PubMed1991

The in vivo immunomodulatory effects of recombinant interferon gamma plus recombinant tumor necrosis factor-alfa.

We conducted a phase I study in which an intramuscular injection of interferon gamma (IFN gamma) at 10, 50, or 100 micrograms/m2 was followed 5 minutes later by an intramuscular injection of 10, 50, or 100 micrograms/m2 of tumor necrosis factor-alfa (TNF alpha) at another site every other day for 20 days (10 doses). The addition of TNF alpha to IFN gamma reduced both the magnitude and duration of IFN gamma-mediated effects on peripheral blood monocyte expression of Fc receptors (FcRs) and HLA-DR and production of hydrogen peroxide. This inhibition was related to the dose of TNF alpha. On the other hand, TNF alpha and IFN gamma appeared to have an additive stimulatory effect on the production of neopterin by monocytes. The highest serum levels of neopterin were detected in patients who received the highest doses of both IFN gamma and TNF alpha. Thus, conflicting conclusions regarding the effect of the combination on immune activation are possible. If the activation of peripheral blood monocytes is the appropriate surrogate measure of the immune enhancement of the combination, then the simultaneous administration of IFN gamma and TNF alpha is ineffective, and future attempts to exploit the potential additive or synergistic effects of this combination of cytokines in humans may need to explore sequential administration schemata. On the other hand, if serum neopterin levels are a more reliable index of immune activation, simultaneous administration of 100 micrograms/m2 IFN gamma and 50 micrograms/m2 TNF alpha every other day (the maximally tolerated dose [MTD]) should be used in phase II testing. This dilemma points out the limitations of currently available methods of human immune assessment and the inadequacies in our capacity to gauge what particular immune measure or set of measures predict for in vivo antitumor effects.

Analysis of Variance↗
PubMed1991

Development of a self-theory and measurement scale.

In this study, we examined a theoretical model of self-development and a scale to measure 12 aspects of the self. The theory, called developmental self-theory, proposes a hierarchical arrangement of dimensions of the self. The 12 scales are collectively called the Omnibus Self-Test and measure Self-Esteem, Positive Self-Regard, Moral Self-Concept, Self-Confidence, Self-Reliance, Self-Control, Selfishness, Self-Disclosure, Self-as-Agent, Self-Critical, Self-Identity, and Self-Reflection. Preliminary data on the reliability and validity of the Omnibus Self-Test is reported along with intercorrelations among the scales.

Adult↗
PubMed1991

Purification and some properties of the tungsten-containing carboxylic acid reductase from Clostridium formicoaceticum.

Judged by properties observed during the purification and based on the sequence of the first 25 amino acids, the enzyme from Clostridium formicoaceticum catalysing the reversible reduction of non-activated carboxylic acids to aldehydes at the expense of reduced viologens, is astonishingly different from that found by us in C. thermoaceticum. According to native and SDS gel electrophoresis the reductase is nearly homogeneous after only 26-fold purification. The specificity for various substrates and artificial electron carriers is also broad, but V of the purified aldehyde dehydrogenase activity (54 U/mg enzyme for butanal) is about 1 order of magnitude lower than that of the enzyme from C. thermoaceticum. The reductase is a dimer of two identical subunits with an Mr of 67,000 each. Increased enzyme concentrations seem to lead to higher oligomers. Per dimer 11 +/- 1 iron, 16 +/- 1 acid labile sulphur, 1.4 tungsten and after permanganate oxidation 1.6 mol pterin-6-carboxylic acid have been found.

Aldehyde Dehydrogenase↗
PubMed1991

[Should one teach ocular surgery?].

Teaching is an obligation for all active ophthalmic surgeons. It is mainly by helping our students to avoid our errors that we can help the progress of medicine. Insofar as ophthalmology is a science it can be taught. An ophthalmic surgeon must not only know how to wield the knife, but also have a sound knowledge of optics and statistics. The choice of a pupil in ophthalmic surgery is mainly a question of character because the power and success of surgery can have a deleterious influence on the morals of a doctor.

Humans↗
PubMed1991

[Detection of antibodies against the larva of Anisakis simplex in the pollock Pollachius virens using ELISA].

From the fact that older saithes (more than 5 years old) are showing significantly lower prevalence of attack by Anisakis larvae in lateral muscle than younger saithes (3-4 years old), the question arises if this phenomenon is based on a specific immune response. Therefore we have investigated serum samples from saithes of different ages by using an indirect ELISA to estimate the antibody-titer against excretory-secretory Anisakis antigen. Results showing a moderate correlation (r = 0.66) between the height of titer and the age of underfeeding saithes (post spawning) and a close correlation (r = 0.93) of saithes in an optimal condition (pre spawning). It may be concluded that the migration-distance and the lifetime of Anisakis larvae in lateral-muscle is influenced by a specific immune response which increases with the age of the saithes.

Age Factors↗
PubMed1991

[Impairment of the cognitive faculties and the reaction capability caused by midazolam despite reversal using flumazenil].

Imidazobenzodiazepine (flumazenil) is a specific competitive benzodiazepine antagonist. It antagonizes the sedative-hypnotic, anticonvulsive, anxiolytic and the muscle-relaxant effects of benzodiazepines. Its efficacy is prompt and complete. In several studies rebound phenomena have been observed. It was the aim of this randomized double blind study to investigate the efficacy of flumazenil by psychometric tests. The psychometric parameters we used were cognition and choice reaction time of 12 young and healthy volunteers. Three medication groups (A, B and C) were formed for this investigation. In a cross over design all volunteers had to be treated in each of these three medication groups. Between the groups we set a test-free interval of 7 days for every volunteer. In medication group A (midazolam/flumazenil) we applied 15 mg midazolam. Reversion was performed after 60 min with 0.5 mg flumazenil. In medication group B (placebo/flumazenil) midazolam was replaced by a physiological solution of sodium chloride. In medication group C (placebo/placebo) midazolam and flumazenil were substituted by a physiological solution of sodium chloride. For the investigation of the psychometric parameters (cognition and choice reaction time) we used the so called syndrome kurz test (SKT) and the decision reaction time measuring instrument ("Entscheidungs-Reaktionszeit-Messgerät"; ERM). Psychometric investigations were performed in all groups at intervals of 5, 30, 60, 90, 120, 180 and 240 min. Our results show that cognitive abilities remain impaired up to 60 min after the administration of flumazenil. Decision time and choice reaction time improved 120 min after administration of the antagonist. In our investigation neither rebound phenomena nor agonistic reactions of flumazenil were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

A human immunoglobulin kappa orphon without sequence defects may be the product of a pericentric inversion.

The VK gene segments that have been transposed from the kappa locus on the short arm of chromosome 2 at 2p11-12 to other chromosomal sites are called orphons. The 18 VK orphons sequenced up to now carry defects and are to be considered pseudogenes. We now describe the VKI gene segment V108 whose sequence is without any defects and which was localized to the long arm of chromosome 2 at 2q12-14 by in situ hybridization. The V108 region may have been transposed from the short to the long arm of chromosome 2 by a pericentric inversion. Possible reasons for the conservation of its sequence are discussed. In spite of its bona fide sequence V108 is considered to be an unlikely candidate for a VK-JK rearrangement and subsequent functional expression.

Amino Acid Sequence↗
PubMed1990

Dandy-Walker variant malformation, spastic paraplegia, and mental retardation in two sibs.

Two sibs, a boy and a girl, had both hypoplasia of the cerebellar hemispheres and partial agenesis of the cerebellar vermis with normal communication between the fourth ventricle and arachnoid spaces, i.e., the manifestations of the Dandy-Walker variant malformation associated with agenesis of the corpus callosum. Both sibs were mentally retarded and had spastic paraplegia. The occurrence of a distinct and similar pattern of congenital anomalies in sibs born to healthy parents points toward a "new" syndrome caused by the homozygous state of an autosomal recessive gene. Prenatal ultrasonographic diagnosis is possible at least for the more severe form of the brain anomalies.

Brain↗
PubMed1990

Recombinant interferon-alpha-2C in chronic myelogenous leukaemia: relationship of sensitivity of committed haematopoietic precursor cells in vitro (BFU-E, CFU-GM, CFU-Meg) and clinical response.

In an ongoing phase-II trial we aimed to predict clinical responsiveness of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML) to recombinant IFN-alpha-2C (rIFN-alpha-2C) by pretesting in vitro. From five normal controls and 14 CML patients in chronic phase, bone marrow samples were taken before treatment and tested for antiproliferative activity by rIFN-alpha-2C, using a microagar culture system for BFU-E, CFU-GM, and CFU-Meg. Light-density nucleated bone marrow cells were stimulated for BFU-E and CFU-Meg colony formation with Alpha medium containing 20% serum obtained from a patient with severe aplastic anaemia. CFU-GM growth was induced with conditioned medium from the cell line GCT. In normal controls BFU-E, CFU-GM and CFU-Meg colony formation was inhibited by rIFN-alpha-2C in a dose-dependent manner. BFU-E proved to be the most sensitive cell lineage (IC50: 65; range: 53-116 U/ml) whereas CFU-GM was about 20 times less sensitive (IC50: 643; range: 480-897 U/ml). The sensitivity of CFU-Meg ranged between these two colony types with 50% growth inhibition at an IFN concentration of 160 (range: 68-246 U/ml). A heterogeneous response to rIFN-alpha-2C in vitro was seen in CML patients. Three of the 14 patients were 'resistant' to rIFN-alpha-2C in vitro with IC50 values for BFU-E, CFU-GM and/or CFU-Meg colony formation greater than 10(4) U/ml. Patients were subsequently treated with a daily dose of rIFN-alpha-2C of 5 x 10(6) U. Four patients achieved a complete and six achieved a partial haematological response. Of the four non-responders three rapidly progressed into blastic crisis. Thus it was seen that treatment failure to interferon was accompanied by IFN-resistance in vitro of BFU-E, CFU-GM and/or CFU-Meg colony formation by bone marrow precursors (p less than 0.01). These results suggest a predictive value of IFN-sensitivity testing in vitro in Ph1 + CML.

Adult↗