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Biomedical subjects

I Krause

Publications and source records attributed to I Krause.

At least 55 records · Page 3Linked to original sources

MRI meningeal enhancement with intracranial hypotension caused by lumbar puncture.

A 12-year-old girl with recent history of pseudotumor cerebri developed severe postural headache due to intracranial hypotension after lumbar puncture. Meningeal enhancement and thickening were demonstrated on magnetic resonance imaging. Repeated imaging 3 months later disclosed no abnormalities. This is the first report of a child with evident meningeal enhancement on magnetic resonance imaging related to lumbar puncture.

Child↗

New methods of treatment in an experimental murine model of systemic lupus erythematosus induced by idiotypic manipulation.

In this article we have presented our experiences and those of others with various experimental and novel treatments in an experimental model of murine SLE, induced by immunisation with pathogenic anti-DNA antibody (fig 4). Many of the treatments (summarised in the table) were highly effective in ameliorating clinical, serological, and histological manifestations of the disease. According to our results, it seems that hormonal treatments--such as testosterone metabolites, anti-oestrogens, or bromocriptine--as well as immunomodulation with IVIG or anti-CD4 antibodies, hold the most promising potential for application in lupus patients. We believe, therefore, that these types of treatment should receive high priority in human trials. It should be emphasised, however, that the timing of treatment may be critical, since several treatments were effective when used before or during the induction of the disease. This limitation may pose difficulty for human application, since the aetiology of SLE is still obscure and is probably multifactorial38; therefore it is not yet possible to identify patients at risk of developing SLE. Nevertheless, those treatments which proved to be effective might be used early in the course of the disease in lupus patients and hence influence the outcome of the disease, or may even induce partial or complete remission.

Animals↗

Seasons of the year and activity of SLE and Behcet's disease.

Patients with systemic lupus erythematosus (SLE) were evaluated using a telephone questionnaire on the activity of various disease manifestations during the seasons of the past year. The results were compared to those of patients with Behcet's disease (BD), using the same questionnaires, and analyzed in relation to the mean temperature, humidity, barometric pressure, and ultraviolet radiation (UVR) in the patient's location, obtained from the official Israeli Meteorological Service. It was found that SLE patients had a tendency towards winter worsening of clinical manifestations, shown as increased incidence of joint pains, weakness, fatigue, Raynaud's phenomenon, and rash, as well as increased number of hospital admissions, sick leaves, and need to raise the dose of medications. The symptoms of patients with BD were not correlated to seasons of the year, except for increased joint pains in autumn and spring. We suggest that UVR accumulation might cause exacerbations in SLE patients several months after prolonged exposure to sunlight in the summer.

Adult↗

The pathogenic role of anti-phosphatidylserine antibodies: active immunization with the antibodies leads to the induction of antiphospholipid syndrome.

Primary antiphospholipid syndrome (pAPS) can be experimentally induced in mice by immunization with anti-cardiolipin (aCL) antibodies (Abs). Recently, we have pointed to the pathogenic role of antiphosphatidylserine (aPS) Abs by inducing an experimental model of pAPS in naive mice following passive transfer of human aPS to the tail vein of ICR mice. The aim of the present study was to induce experimental pAPS in mice following active immunization with aPS. Mice were immunized with IgG and IgM aPS, purified from two patients with pAPS. The sera of the mice were examined for the presence of different antiphospholipid Abs, and the beta 2 GPI dependency of aPS, using an enzyme-linked immunosorbent assay (ELISA). Inhibition ELISA studies, with silica beads coated with phospholipids, were used to detect cross-reactivity of aPS or aCL to other phospholipids. The mice were also tested for the presence of thrombocytopenia, prolonged activated partial thromboplastin time (APTT), and the percentage of fetal resorptions. The purified IgG aPS but not IgM aPS had a strong lupus anticoagulant activity. Both IgG and IgM aPS were beta 2 GPI dependent and did not bind PS in the absence of the glycoprotein. The mice immunized with IgG aPS, but not IgM aPS, developed high titers of mouse aPS. The mice generated polyspecific Abs, cross-reacting with aCL and aPS, as well as individual aPS or aCL Abs. Only the mice immunized with IgG aPS developed clinical parameters of pAPS: prolonged APTT, thrombocytopenia, and an increased fetal resorption rate. In conclusion, active immunization with IgG, but not IgM, aPS induces experimental pAPS in naive mice, thus pointing to the participation of aPS in the idiotypic network.

Adult↗

Determination of biogenic amines by RP-HPLC of the dabsyl derivates.

An automated derivatization with dabsyl chloride in combination with a high-performance liquid chromatographic analysis is described for the determination of biogenic amines in complex matrices. The sample clean-up procedure consists of an ultrafiltration step, resulting in average recoveries for cheese in the range of 88% to 100%. A linear relation between the area of the peak and amine concentration was observed between 0.5 and 500 pmol for all amines under investigation and the detection limits ranged between 0.34 and 0.76 pmol. The average repeatability of both the performance of the chromatographic determination and the whole method, including sample preparation, examined using cheese samples containing different amounts of biogenic amines was found to be between 2.0% and 3.7%. The method was applied to the analysis of several types of food and feed, selected examples are given by the separation of dabsyl derivates from cheese, wine, and salami-type sausage.

Animal Feed↗

Isolation and rapid sequence characterization of two novel bovine beta-lactoglobulins I and J.

Two novel bovine beta-lactoglobulins I and J have been isolated from bovine milk and characterized by isoelectric focusing. Their primary structure was determined by a very rapid method consisting of a combination of Edman sequencing, mass analysis, and ladder sequencing by mass spectrometry. We found that both new beta-lactoglobulins are of the bovine beta-lactoglobulin B-variant type. beta-lactoglobulin I shows Gly instead of Glu at position 108, whereas beta-lactoglobulin J shows a Pro-to-Leu exchange at position 126.

Amino Acid Sequence↗

Acute haemorrhagic oedema of infancy, a benign variant of leucocytoclastic vasculitis.

Acute haemorrhagic oedema of infancy (AHEI) is an acute leucocytoclastic vasculitis affecting infants and young children. It has a striking appearance of large purpuric skin lesions in a target-like pattern and marked oedema mainly on the face, auricles and extremities. In some patients there is mucosal involvement as well. We present five patients with skin lesions characteristic of AHEI with no visceral involvement and complete resolution within 7-14 days. In three of our five cases, histopathological examination was performed, and demonstrated typical leucocytoclastic vasculitis. Although sometimes confused with Schönlein-Henoch purpura, we suggest that AHEI should be regarded as a separate entity. Clinical criteria for diagnosis are proposed.

Adult↗

Treatment of systemic lupus erythematosus and antiphospholipid syndrome: from experimental models to patients' bedside.

Animal models are of great value in the evaluation of novel and experimental treatments that cannot be tested directly on patients. In this article, we summarize the spectrum of murine models for systemic lupus erythematosus and antiphospholipid syndrome, focusing on animal models based on idiotypic immunization. Several therapeutic modalities that have been tested in those models had promising potential for application in human patients.

Animals↗

Immunomodulation of experimental APS: lessons from murine models.

During the last few years several murine models for APS have been described. These include spontaneous occurring disease, or APS induced by immunization with pathogenic autoantibodies. Employing those models, several treatment modalities, in different stages of the disease, were studied. Treatments which showed promising potential for application in patients with APS include immunomodulation with specific anti-idiotypic or anti-CD4 antibodies, treatment with IL-3, high-dose intravenous immunoglobulins, ciprofloxacin or bromocriptine, as well as antithrombotic and anticoagulant treatments using aspirin and/or low-molecular-weight heparin. Bone-marrow transplantation was also found to improve clinical and serological manifestations of the disease. These studies might promote the handling of controlled clinical trials assessing their efficacy in APS patients.

Animals↗

Bromocriptine immunomodulation of experimental SLE and primary antiphospholipid syndrome via induction of nonspecific T suppressor cells.

Bromocriptine (BRC) is a dopamine agonist that suppresses the secretion of prolactin by the pituitary gland and is known to have immunomodulating properties. In the present study, we investigated the effect of BRC on the development of two autoimmune experimental models: (i) systemic lupus erythematosus (SLE), induced by injection of a human anti-dsDNA monoclonal antibody (MIV-7); (ii) primary anti-phospholipid syndrome (PAPS), induced by injection of a mouse anticardiolipin monoclonal antibody (CAM). BRC had a suppressive effect on in vivo autoantibody production, as well as on the appearance of other manifestations of the respective disease. The BRC activity seems to be nonspecific, since the same effect was demonstrated in mice with lupus and with PAPS. These data were supported by the in vitro nonspecific effect of CD8 cells induced in vivo by bromocriptine, on specific lymph node cell proliferation in the presence of the pathogenic monoclonal antibodies (MIV-7 or CAM, respectively), and on the response to an irrelevant autoantigen, myelin basic protein. These data were complemented by the nonspecific suppressive effect by the T-suppressor factor, produced by the CD8 cells, on specific thymidine uptake by lymph node cells from experimental SLE or PAPS in the presence of the immunizing mAb. Injection of CD8 cells from BRC-treated mice with SLE or PAPS abolished the disease development in the lupus and PAPS experimental models. The data suggest a possible novel role of bromocriptine in downregulating autoimmune phenomena through induction of natural nonspecific CD8+ suppressor cells.

Animals↗

[Non-ketotic hyperglycinemia].

Three children with non-ketotic hyperglycinaemia (NKH) is reported. Two patients had typical neonatal form of NKH, one patients had atypical form of NKH. The clinical symptoms laboratory findings and therapeutical approach are discussed. One of the patients with typical neonatal form of NKH is died, neuropatological examination revealed corpus callosal agenesis and diffuse hypomyelinisation. The two children treated with N-methyl-D-aspartate-antagonist drugs reached a significantly better clinical condition. The authors reviewed the data of the literature, especially focused on the therapeutical possibilities.

Amino Acid Metabolism, Inborn Errors↗

Transfer of experimental antiphospholipid syndrome by bone marrow cell transplantation. The importance of the T cell.

OBJECTIVE: To investigate the potential of bone marrow cells from mice with primary antiphospholipid syndrome (APS) to transfer the disease to naive mice, and to determine the importance of the role of T cells in the APS. METHODS: Experimental primary APS was induced in naive mice following active immunization with anticardiolipin (aCL) monoclonal antibody (MAb). Whole-population or T cell-depleted bone marrow cells from mice with experimental primary APS were infused into total body-irradiated naive BALB/c recipients. RESULTS: Bone marrow cells (in the presence of T cells) had the potential to induce experimental APS in naive mice, which resulted in high serum titers of aCL, antiphosphatidylserine, and antiphosphatidylinositol antibodies; an increased number of antibody-forming cells specific for each of the above phospholipids; a positive lymph node cell proliferative response to aCL MAb; and clinical features of primary APS, including thrombocytopenia, prolonged activated partial thromboplastin time (indicating the presence of lupus anticoagulant), and a high frequency of fetal resorptions (the equivalent of human fetal loss). T cell-depleted bone marrow cells did not transfer the disease. CONCLUSION: This study demonstrates the important role of T cells in the development and transfer of experimental primary APS and raises the possibility of T cell manipulations in treatments to prevent this condition.

Animals↗

Fate of the upper urinary tract in multiple sclerosis.

Urologic problems are a major source of morbidity for patients with multiple sclerosis (MS). Fifty-four to 78% of patients experience bladder symptoms which are due to spinal lesions interrupting neural pathways that control micturition. MS patients could have upper or lower motor neuron lesion type bladders. Both obstructive and irritative symptoms may be present. Although lower urinary tract dysfunction has been well described in MS, few studies have investigated the fate of the upper urinary tract. Thirty-two patients with MS were referred for urodynamic evaluation. Twenty-six of the 32 patients had upper urinary tract studies performed. Only 1 of the 26 patients had evidence of upper urinary tract deterioration. It is our impression that upper tract deterioration occurs infrequently in these patients. We discuss clinical clues that may predict deterioration.

Adult↗

Absence of anti-idiotypic antibodies in IVIG preparations to autoantibodies of rare autoimmune diseases.

Intravenous immunoglobulins (IVIG) were found to contain anti-idiotypic antibodies against autoantibodies of various autoimmune diseases. We examined commercial IVIG preparations, from three different manufactures, for the presence of autoantibodies and anti-idiotypic antibodies of two rare autoimmune diseases--primary biliary cirrhosis [anti-pyruvate dehydrogenase (PDH) antibodies] and Goodpasture's syndrome (anti-NC1 antibodies). We used ELISA studies as well as immunoblotting and anti-PDH enzyme activity for the detection of anti-PDH antibodies. ELISA and immunofluorescence studies were used for the detection of anti-NC1 antibodies. The presence of anti-idiotypic activity against anti-PDH fragments on Sepharose-bound IVIG [F(ab)2]. Anti-anti-NC1 activity was evaluated employing inhibition ELISA and immunofluorescence studies. The commercial IVIG preparations that were examined did not contain anti-PDH or anti-NC1 antibodies nor anti-idiotypic activity against these autoantibodies. We conclude that commercial IVIG may lack anti-idiotypic activity against rare autoantibodies.

Anti-Glomerular Basement Membrane Disease↗

Abrogation of experimental systemic lupus erythematosus and primary antiphospholipid syndrome with intravenous gamma globulin.

OBJECTIVE: To evaluate the effect of intravenous gamma globulin (IVGG) treatment on the immunological and clinical manifestations of experimental systemic lupus erythematosus (SLE) and primary antiphospholipid syndrome (APS). METHODS: BALB/c mice were actively immunized with anti-DNA (MIV-7) monoclonal antibodies (Mab) or anticardiolipin (aCL, CAM) Mab, to induce experimental SLE and primary APS, respectively. Eight weeks after immunization the mice were treated for 6 weeks with IVGG (whole molecule), F(ab')2, or Fc fragments. The following studies were carried out: autoantibody profile (ELISA), clinical manifestations including erythrocyte sedimentation rate (ESR), white blood cell and platelet count, immunoglobulin deposits in the kidneys, and fetal resorptions. The presence of antiidiotypic activity to anti-DNA and aCL antibodies in the IVGG was determined by inhibition studies employing the F(ab')2 as inhibitor. RESULTS: Following treatment with IVGG or IVGG F(ab')2, a complete clinical remission, manifested as normal ESR and leukocyte counts, and lack of proteinuria or immunoglobulin deposits in the kidneys in the mice with experimental SLE, normal activated partial thromboplastin time, and fetal resorption rate in the mice with experimental primary APS was achieved. Autoantibody titers in the mice decreased to within normal levels. Treatment with Fc fragments had no effect upon those variables. Inhibition studies pointed to the presence of antiidiotypic activity to anti-dsDAN and aCL antibodies in the IVGG preparation. CONCLUSION: Treatment with IVGG can lead to clinical and immunological remission in mice with experimental SLE and primary APS. This effect may be carried out through manipulation of the idiotypic network and neutralization of pathogenic autoantibodies. Our results may justify the use of IVGG in patients with SLE and/or APS.

Animals↗