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Biomedical subjects

I Böhm

Publications and source records attributed to I Böhm.

At least 19 recordsLinked to original sources

[The apoptosis marker enzyme poly-(ADP-ribose) polymerase (PARP) in systemic lupus erythematosus].

The enzyme poly-(ADP-ribose) polymerase (PARP) is localized within the cell nucleus and catalyzes DNA-repair. During programmed cell death (apoptosis), PARP is enzymatically cleaved. Detection of the cleavage products is characteristic for apoptosis. In patients with systemic lupus erythematosus (SLE), the highly ordered signal transduction cascade of apoptosis is disturbed. SLE patients show reduced PARP activity . PARP cleavage products are mainly found in association with either antinuclear and/or anti-dsDNA antibodies. In addition, serum samples from SLE patients and other autoimmune diseases display anti-PAR and anti-PARP autoantibodies.

Antibodies, Antinuclear↗

[Molecular imaging of apoptosis and necrosis -- basic principles of cell biology and use in oncology].

Soon molecular imaging techniques will play a prominent role in basic scientific research and clinical approaches. In particular, important aspects of medicine such as apoptosis and gene- and stem-cell therapy will play a pivotal role in radiology too. This review presents the basic principles of apoptosis, recent results and future perspectives of apoptosis imaging. Apoptosis or programmed cell death is a precisely regulated, complex cascade of molecular events to eliminate individual cells. Disturbances may lead to diseases like malignancies and neurodegenerative diseases that are of clinical relevance. Several therapeutic strategies in oncology are based on apoptosis induction; conversely, resistance to therapy is indicative of decreased apoptosis induction. Whereas up to now the clinician had to depend exclusively on biopsy specimens to detect apoptosis, the feasibility of non-invasive imaging of this cell-biological phenomenon in vivo opens up new horizons in future. This review focuses on different modifications of this imaging technique, with and without the use of molecular probes (e. g. annexin V, synaptotagmin I), in vitro and in vivo using the various detector systems (like MRI, flow cytometry) currently available. Future perspectives are also addressed.

Animals↗

[Non-ionic iodinated dimeric versus monomeric X-ray contrast media: effects on complement factors in vivo].

PURPOSE: To survey contrast media (CM)-induced alterations of complement factors. MATERIAL AND METHODS: In 31 adult patients, who received either an iotrolan (n = 19) or iopromide (n = 12) i. v. injection for CT examination, complement factors C1 q, C3, C4, C5 a, and C1-esterase inhibitor in serum/plasma samples were analyzed. The samples were obtained prior to and 5 min., 30 min., 1 hr., 6 hrs. and 24 hrs. after CM injection. RESULTS: 5 patients (16.1 %) developed a CM reaction. 4 of these were patients who received iotrolan. Other than minimal data, we neither found a significant influence of the CM on complement activation nor a difference between the analyzed CM. In detail, 5 min. after CM administration, we found the tendency to be for the values to decrease and then to return to the basic value. The changes induced by iotrolan were more pronounced than those induced by iopromide; nevertheless the differences were not statistically significant. A more pronounced decrease of C3 and C4 after iotrolan injection indicates the activation of the classic way, while this could not been observed after iopromide injection. One patient who experienced an unwanted reaction towards iotrolan showed shifts of C1 q, C1 INH, C3 and C4. CONCLUSION: The presented data shows different influences of CM injection on the analyzed complement factors after 5 min. that were commonly no longer present 30 min. after CM injection. The dimeric iotrolan induced a significantly increased frequency of unwanted CM reactions than the monomeric iopromide. The question of whether iotrolan is possibly able to activate the classic way of the complement cascade should be analyzed in the future in a greater patient group.

Adult↗

Apoptosis: the link between autoantibodies and leuko-/lymphocytopenia in patients with lupus erythematosus.

OBJECTIVE: To analyse the relation between serum autoantibodies and leuko-/lymphocytopenia in patients with lupus erythematosus (LE). METHODS: Laboratory routine analyses (white blood cell counts, autoantibody detection), and flow cytometry (annexin V, CD3, CD4, CD8, CD95, F(ab)2 anti-human IgG) have been performed in LE-patients versus healthy controls. In vitro, the influence of pooled serum containing anti-dsDNA antibodies has been analysed on the CD95 expression. RESULTS: Leukocytes, lymphocytes, CD3+, CD3+ CD4+, and CD3+ CD8+ cells from LE-patients were significantly reduced compared with controls. Patients with autoantibodies had significantly lower absolute cell counts than those without. Apoptosis was increased in LE versus controls (p < 0.04). The percentage of CD95+ T-cells was increased, and the absolute number of CD95+ cells was reduced in LE. In vitro up-regulation of CD95 could be detected on T-cells of healthy donors. Induction of CD95 seems to be donor-dependent. CONCLUSION: The data suggest that autoantibodies may be associated with blood cytopenias. CD95 seems to play a central role in this signalling cascade. The underlying mechanism is unclear, but seems to be autoantibody-related apoptosis induction.

Adolescent↗

Revision surgery after failed unicompartmental knee arthroplasty: a study of 35 cases.

This retrospective study evaluates the results of 35 revision procedures after failed unicompartmental knee arthroplasty (UKA) in 34 patients, which were done during the period 1986 to 1996. There were 28 women and 6 men with a mean age of 71 years (range, 54-85 years). In all cases, St. Georg and Endo (W. Link, Hamburg, Germany) unicompartmental prostheses were used except 1 PCA unicondylar implant (How medica, Rutherford, NJ) and 1 Böhler unicondylar implant (Allo Pro, Baar, Switzerland). Failures most frequently were due to aseptic loosening followed by polyethylene wear. Two deep infections occurred. Revisions were performed 1 week to 11 years after UKA; 23 were required within the first 5 years. In most cases, revision was to a total knee arthroplasty. Partial component exchange was done in 9 cases. All 34 patients were evaluated clinically after exchange arthroplasty. After a mean follow-up time of 4 years (range, 1-12.2 years), we found 11 excellent, 13 good, 4 fair, and 7 poor results according to the Hospital for Special Surgery score. The fair and poor results were due to aseptic loosening of the knee prosthesis in 6 knees. One of 2 patients with deep infection needed femoral amputation. With correct indication and considerable surgical experience, UKA is still a good alternative, especially in the elderly patient.

Aged↗

[Successful therapy of an ILVEN in a 7-year-old girl with calcipotriol].

A 7-year-old otherwise healthy girl presented with a 2-year history of an ILVEN (inflammatory linear verrucous epidermal nevus) located on the inner part of her right upper arm. The diagnosis was histologically confirmed. Different conservative therapeutic strategies with corticosteroids, antibiotics and antimycotics produced little or no improvement. Because of encouraging reports describing the successful use of 0.005% calcipotriol ointment in patients with ILVEN, we treated our patient with this regimen. After 4 weeks we could recognize a impressive improvement and after 8 weeks the ILVEN had nearly completely disappeared. 25 weeks after withdrawal of calcipotriol, no relapse had occurred. The dramatic response to calcipotriol suggests some pathological links between ILVEN and psoriasis.

Administration, Topical↗

[ANCA-positive lupus erythematodes profundus. Successful therapy with low dosage dapsone].

A 44-year-old male patient with lupus erythematosus profundus (lupus panniculitis) (LEP) of the right cheek/infraorbital region presented as a recurrent swelling. He had only anti-neutrophil-cytoplasmic antibodies (ANCA), which have not been previously described in association with LEP. There was no indication of systemic lupus erythematosus. While chloroquine produced no benefits, the skin lesions promptly cleared with dapsone. Step by step we reduced dapsone to a final dose of 50-75 mg per week. The ANCA titer decreased in parallel to the clinical improvement.

Adult↗

Engineering of a minimal modular polyketide synthase, and targeted alteration of the stereospecificity of polyketide chain extension.

BACKGROUND: Polyketides are a large and structurally diverse group of natural products that include antibiotics, antifungal agents and immunosuppressant compounds. Polyketides are biosynthesised in filamentous bacteria on modular polyketide synthases (PKSs) in which each cycle of chain extension requires a different 'module' of enzymatic activities. The recently proposed dimeric model for modular PKSs predicts that even a single-module PKS should be catalytically active in the absence of other PKS components. Researchers are also interested in manipulating the stereochemical outcome of polyketide chain extension using genetic engineering of domains within each module. RESULTS: We have constructed a minimal modular PKS from the erythromycin-producing PKS (DEBS) of Saccharopolyspora erythraea. The diketide synthase (DKS1-2) consists of a single chimaeric extension module, derived from the DEBS module 1 ketoacyl-ACP synthase (KS), sandwiched between a loading module and a chain-terminating thioesterase. When DKS1-2 was expressed in S. erythraea, the strain preferentially6 accumulated the diketide (2R, 3S)-2-methyl-3-hydroxy pentanoic acid. CONCLUSIONS: These results demonstrate that, as predicted, even a single-module PKS is catalytically active in the absence of other DEBS proteins. In its normal context, the ketosynthase domain KS1 is thought to generate a (2S)-2methyl-3-hydroxy intermediate by epimerising the initial product of carbon-carbon chain formation, the (2R)-2-methyl-3-ketoester. The observed formation of the alternative (2R)-methyl-3-hydroxy product catalysed by DKS1-2 provides strong support for this proposal, and indicates how targeted alteration of stereospecificity can be achieved on a modular PKS.

Dimerization↗

[Intracytoplasmic injection (ICSI) of cryopreserved testicular spermatozoa (Cryo-TESE): a retrospective study of the first 250 treatment cycles].

It is reported on the results of 250 treatment cycles in which we carried out intracytoplasmic injections (ICSI) with frozen and thawed testicular spermatozoa (cryo-TESE). Up to July 1997 we treated 127 patients, 225 embryo transfers were performed (90%), and an average of 2.3 preimplantation embryos were transferred. This resulted in 53 clinical pregnancies, six patients aborted (11.3%). The pregnancy rate was 21.2% per treatment cycle, 23.5% per embryo transfer, and 41.7% per patient. This so called cumulative pregnancy rate is still about to rise, because 49 out of the 72 non-pregnant patients are still in our ICSI-program. Twenty-two children are born, 2 twins and 1 triplet. All children are healthy and without any major malformations. We conclude from these results that using cryopreserved testicular sperm for ICSI is an effective and successful approach for the treatment of severe testicular insufficiency. In comparison to the use of native testicular sperm with the necessity of repetitive testicular biopsies, cryopreservation is advantageous in many concerns (e.g. logistic, organisatoric and financial) and is therefore recommended for clinical routine.

Female↗

A paternity case with apparently conflicting multilocus and single-locus DNA typing results.

A paternity case is presented in which DNA typing with thirteen variable number of tandem repeat (VNTR) systems was in apparent conflict with an initial multilocus DNA analysis using oligonucleotide probe (CAC)5. A dual approach was necessary, because the multilocus analysis yielded a proportion of aberrant nonmaternal offspring bands far too small and level of band-sharing too high for non-paternity. The case could finally be solved by reference to the joint likelihood ratio combining both approaches. Arguments are presented that summation of log likelihoods is indeed valid even if no information is available regarding linkage between the VNTR loci and the loci contributing to a multilocus DNA fingerprint.

DNA↗

[Th1 cells, Th2 cells and atopic dermatitis].

The immunological hallmark of atopic dermatitis (AD) is a Th1/Th2 dysbalance. The reaction to high molecular weight environmental allergens (e.g. pollen, house dust mites), production of IgE and activation of eosinophil granulocytes result from Th2 dominance. The Th2-cytokine interleukin-4 (IL-4) is necessary for IgE synthesis. Additionally, IL-4 inhibits the generation of Th1-cells. The marker cytokine of Th1-cells, interferon gamma (IFN gamma), exhibits reciprocal effects. It inhibits IgE synthesis and Th2 expansion, but supports Th1-cell growth. Beside the well known mechanisms of IgE-mediated immediate type reactions, the relevance of IgE for the pathogenesis of AD seems to be likely since the discovery of IgE-receptors upon Langerhans cell surfaces. Langerhans cell-bound IgE may be possibly necessary for the presentation of high molecular weight aero-allergens. Analyses of Th subsets at different intervals after allergen challenge showed, that Th2-cells play an important role in the initial phase of inflammatory reactions whereas in later stages Th1-cells can be detected in greater numbers.

Allergens↗

[Treatment of bullous pemphigoid with low-dose methotrexate].

Three patients with biopsy-proven bullous pemphigoid (BP) and anti-basement-membrane antibodies were treated weekly with low-dose methotrexate (MTX) 12.5-25 mg. To accelerate recovery we initially combined MTX with systemic and/or topical corticosteroids. In combination with MTX, the initial dose of 32 mg corticosteroids/day was sufficient. In all 3 patients the BP disappeared within 4 weeks. To maintain this beneficial effect, very low doses of MTX (25 mg every other week or every four weeks) suffered. Opportunistic infections did not appear. Laboratory tests during MTX-treatment revealed no immunosuppression. The treatment was well tolerated; we could neither observe subjective problems nor other pathologic changes. There are several lines of evidence for immunomodulating effects of MTX and the clinical benefit in BP might be possibly due to these actions of MTX. Our data show, that the treatment of BP with low-dose MTX is an effective alternative with a favorable benefit/side-effect ratio.

Administration, Oral↗

Distinct spectrum of CFTR gene mutations in congenital absence of vas deferens.

Congenital absence of the vas deferens (CAVD) is a frequent cause for obstructive azoospermia and accounts for 1%-2% of male infertility. A high incidence of mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has recently been reported in males with CAVD. We have investigated a cohort of 106 German patients with congenital bilateral or unilateral absence of the vas deferens for mutations in the coding region, flanking intron regions and promotor sequences of the CFTR gene. Of the CAVD patients, 75% carried CFTR mutations or disease-associated CFTR variants, such as the "5T" allele, on both chromosomes. The distribution of mutation genotypes clearly differed from that observed in cystic fibrosis. None of the CAVD patients was homozygous for delta F508 and none was compound heterozygous for delta F508 and a nonsense or frameshift mutation. Instead, homozygosity was found for a few mild missense or splicing mutations, and the majority of CAVD mutations were missense substitutions. Twenty-one German CAVD patients were compound heterozygous for delta F508 and R117H, which was the most frequent CAVD genotype in our study group. Haplotype analysis indicated a common origin for R117H in our population, whereas another frequent CAVD mutation, viz. the "5T allele" was a recurrent mutation on different intragenic haplotypes and multiple ethnic backgrounds. We identified a total of 46 different mutations and variants, of which 15 mutations have not previously been reported. Thirteen novel missense mutations and one unique amino-acid insertion may be confined to the CAVD phenotype. A few splice or missense variants, such as F508C or 1716 G-->A, are proposed here as possible candidate CAVD mutations with an apparently reduced penetrance. Clinical examination of patients with CFTR mutations on both chromosomes revealed elevated sweat chloride concentrations and discrete symptoms of respiratory disease in a subset of patients. Thus, our collaborative study shows that CAVD without renal malformation is a primary genital form of cystic fibrosis in the vast majority of German patients and links the particular expression of clinical symptoms in CAVD with a distinct subset of CFTR mutation genotypes.

Adult↗

Comparison of personal history with patch test results in metal allergy.

In order to compare the validity of patient personal history of contact sensitivity to metal alloys with patch test results, 160 patients with hand eczema were patch tested with a standard series according to the ICDRG after a special questionnaire. In 65%, history and patch test results were identical. Seventy-eight (48.8%) patients thought they would be allergic to metal ions, whereas the patch test revealed a positive result in only 21.3% cases. Positive history but negative test was more frequent in women; in the male group, negative history and positive patch test was the most common finding. Although 82 patients had a negative history, the patch test was positive for contact sensitivity to metal allergens in 12 of them. Both false positive patch tests and false negative histories are possible. Since many factors influence a positive patch test, not only the patient's history but also a synopsis of the anamnesis and patch testing will help to achieve the correct diagnosis of metal contact hypersensitivity.

Dermatitis, Allergic Contact↗

Epilepsy and fragile X gene mutations.

We used two strategies to investigate a possible link between predisposition for epilepsy and mutations in the fragile X mental retardation-1 gene. The first entailed performing electroencephalography on 14 patients with an amplification in the fragile X mental retardation-1 gene, and the second involved molecular genetic analysis of the fragile X mental retardation-1 gene in 16 children with benign childhood epilepsy with centrotemporal spikes (BECT, Rolandic epilepsy). Fourteen young male patients with fragile X syndrome, verified by a full mutation in exon 1 of the fragile X mental retardation-1 gene, were studied by electroencephalography. In eight boys aged between 4-8 years we observed focal sharp waves, activated by sleep. In six of these patients, partial seizures occurred during sleep. We detected no epileptiform electroencephalographic abnormalities under the age of 4 and over the age of 8. In 16 children with Rolandic epilepsy who were studied for fragile X gene mutations, one boy proved to carry a fragile X premutation. In the waking state electroencephalography of a 5-year-old girl with a premutation in one of her fragile X mental retardation-1 genes, we found groups of generalized spike wave complexes. Our observations suggest a possible impact of the fragile X mental retardation-1 gene mutations on brain maturation and epileptogenesis.

Adolescent↗

Proteolytic degradation of dinitrogenase reductase from Anabaena variabilis (ATCC 29413) as a consequence of ATP depletion and impact of oxygen.

Both components of nitrogenase, dinitrogenase and dinitrogenase reductase, are rapidly inactivated by oxygen. To investigate the proteolytic degradation of dinitrogenase reductase irreversibly destroyed by high oxygen concentrations, we carried out in vitro experiments with heterocyst extracts from Anabaena variabilis ATCC 29413. The results indicate a direct dependence of degradation on the applied oxygen concentration. Although the degrees of degradation were similar for both the modified and unmodified subunits of dinitrogenase reductase, there was a significant difference with respect to the cleavage products observed. The pattern of effective protease inhibitors suggests the involvement of serine proteases with chymotrypsin- and trypsin-like specificity. A protective effect was obtained by saturation of the nucleotide binding sites of dinitrogenase reductase with either ATP or ADP. As shown by gel filtration experiments, the adenylates prevented the nitrogenase subunits from extensive noncovalent aggregation, which is usually considered evidence for a denaturing process. The in vitro degradation of dinitrogenase reductase is discussed in connection with previous reports on degradation of nitrogenase in cyanobacteria under oxygen stress and/or starvation.

Adenosine Diphosphate↗