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Biomedical subjects

O Schofer

Publications and source records attributed to O Schofer.

30 records · Page 2Linked to original sources

Antibacterial capacity of buccal epithelial cells from healthy donors and children with recurrent urinary tract infections.

The effect of buccal epithelial cells (BEC) on bacterial growth was investigated in healthy subjects as well as in patients with recurrent urinary tract infections (UTI) and compared to the antibacterial capacity of uroepithelial cells (UEC) of the same individuals. Epithelial cells were obtained from the following groups: healthy female controls; females without further UTI after reflux operation; females with asymptomatic bacteriuria (ABU); females with further UTI despite successful reflux operation; and patients with meningomyelocele (MMC) and recurrent UTI due to significant residual urinary volume. Cocultivation of Escherichia coli with BEC as well as UEC from healthy females or patients with MMC resulted in significant suppression of bacterial growth. However, neither type of epithelial cell showed an antibacterial effect when they were obtained from patients with recurrent UTI in the absence of urological abnormalities (ABU patients; reflux-corrected patients with further UTI). From these results it is concluded that a generalised epithelial defence defect is one important pathogeneic factor for recurrent idiopathic UTI.

Adolescent↗

[The effect of Campath-1 on T- and NK-cells].

An assay system capable of detecting 0.03% residual T cells is described. This test system was used to evaluate bone marrow which was treated with Campath-1 and human complement (HC'). All T cell-depleted samples tested were found to be free of OKT3-positive T cells (less than 0.03%). The assay described provides a highly sensitive method for the detection of residual T cells and can be used as an alternative to limiting dilution assays. The results presented here confirm that treatment of donor bone marrow with Campath-1 and HC' provides a highly effective means of removing T cells and thus should be effective in GVHD prevention. However, although Campath-1 effectively depletes T- and B cells, it unexpectedly failed to eliminate cells that display NK function.

Antibodies, Monoclonal↗

Intrathymic tolerance induction: determination of tolerance to class II major histocompatibility complex antigens in maturing T lymphocytes by a bone marrow-derived non-lymphoid thymus cell.

Two new experimental approaches were established to analyse the influence of the thymus on tolerance induction to major histocompatibility complex (MHC) antigens: The aim of the first experiment was to perform successful transplantation of adult allogeneic thymus tissue into nude mice, an attempt that has been unsuccessful in the past. Tolerance for the MHC genotype of a prospective thymus graft recipient (A) was induced in mice of strain B by injection of (A X B) splenocytes during the neonatal period. Adult thymic tissue obtained from these allogeneic donors (B) were grafted into the nude mice of strain A. The allogeneic thymus was accepted by the nude mice and immunoreconstitution was achieved. Subsequently the recipients developed tolerance to the MHC antigens of the allogeneic thymus donor as proved by mixed lymphocyte cultures and the acceptance of skin grafts. The second experiment was designed to determine which Ia-positive thymic compartment participates in conferring tolerance to MHC antigens in maturing T lymphocytes. Chimaeric thymus grafts were created by transplantation of neonatal thymus (A) into allogeneic nude mice (B) for a period of 8 weeks. The graft was populated with host bone marrow-derived Ia antigen-positive cells. The chimaeric thymuses consisting of type A epithelium but populated with both type A and B lymphocytes and non-lymphoid cells (i.e. Ia-positive macrophages and dendritic cells), were newly transplanted into nude mice of strain A. The engraftment lead to immunological reconstitution and the nude mice acquired tolerance to the MHC antigens expressed by the allogeneic Ia-positive cells populating the chimaeric graft. Irradiation of the chimaeric thymus prior to transplantation allowed transplantation of chimaeric thymus devoid of living thymocytes but still populated with functionally intact Ia-positive non-lymphoid cells. Transplantation of irradiated chimaeric thymuses resulted in immunoreconstitution and induced exactly the same allotolerance pattern as described above. The results demonstrate that not thymus epithelial cells but a bone-marrow-derived non-lymphoid thymus cell, most likely the Ia-antigen-positive thymic macrophage of dendritic cell, is responsible for the induction of tolerance to MHC antigens in developing T lymphocytes.

Age Factors↗

[Modulation of graft versus host disease by in vitro incubation of donor cells with deoxycoformycin and deoxyadenosine].

The combination of deoxycoformycin and deoxyadenosine was investigated for its capability to deplete T-cells from bone marrow and spleen cells and for its effect on GVHD in MHC-mismatched transplantation in rats. In vitro incubation with DCF/dADO for 18-20 hours resulted in significant but incomplete T-cell depletion without toxicity towards CFU-M. This corresponded with a lower incidence and a modification of GVHD following transplantation of such treated cells into MHC-incompatible recipient rats. However, GVHD could not be completely prevented by the in vitro treatment of donor cells.

Animals↗

Normomorphic sialidosis in two female adults with severe neurologic disease and without sialyl oligosacchariduria.

Two female patients of German origin, aged 38 and 21 years, with myoclonus epilepsy and cerebellar ataxia, but without dysmorphic signs and dementia, were found to excrete normal amounts of sialyl oligosaccharides in their urine. The younger patient showed cherry red spots in her ocular fundi. The older patient had a brother with an autopsy-proven neuronal storage disease compatible with sialidosis, and in her rectal biopsy lamellar inclusion bodies were detected. Enzyme assays in cultured fibroblasts of both patients revealed a profound but incomplete deficiency of oligosaccharide sialidase activity and normal beta-galactosidase activity. Adult sialidosis was diagnosed in both patients. In their fibroblasts, moderate elevations of bound sialic acid could also be measured. The small residual sialidase activity, which in the older patient had a normal KM value, is considered responsible for the late onset and slow clinical course of the disease. It is concluded that in adult sialidosis the extraneural storage process can be difficult to demonstrate in terms of metabolite accumulation or excretion during the course of intraneuronal storage.

Adult↗

[Immunotherapy in virus diseases].

The number of effective anti-viral agents is still limited. Therefore immunotherapy remains of importance in the treatment of viral infections. Immunoglobulins and interferons as well as a variety of immune stimulators or immune modulators are available. The efficacy of such therapy strongly depends on the kind of the virus causing the infection as well as the time of initiation of the treatment. The prophylactic and therapeutic effects of immunoglobulin preparations are well documented, whereas the efficacy of interferons and especially of immune stimulators awaits further evaluation.

Adjuvants, Immunologic↗

[Clinical course and scar development in operated vesico-renal reflux in a long-term study].

62 patients (14 boys, 48 girls) representing 85 refluxive renal units (Grade 2-4) were investigated after successful operation for the development of further urinary tract infections (UTI) and renal scars (RS). The mean follow-up was 9.3 years. With the exception of one boy, none of the male patients developed any UTI or new RS. A similar result was obtained for about 45% of the girls. These two groups of patients presented with high-grade reflux before surgery. The remaining female patients (about 55%), however, presenting with lower-grade reflux before surgical treatment, developed further UTI as well as new RS despite surgical correction of their reflux. Investigations on the capacity of uroepithelial cells (UEC) to suppress bacterial growth revealed a deficient antibacterial effect of UEC in these patients. Such an UEC defect has also been shown in patients with asymptomatic bacteriuria. In conclusion, different reasons seem to be responsible for recurrent UTI and the development of RS in patients with reflux.

Adolescent↗

[The therapy with immunoglobulins. Structure, mechanisms of action and the intravenous use of gammaglobulin preparations (author's transl)].

With regard to clinical success the therapy with immunoglobulins has to take into account exact therapeutic indications as well as the biological and physical properties of the immunoglobulin preparations being available. This paper summarizes the structure, the biological effects and the therapeutic indications of intravenous applicable immunoglobulin preparations. It becomes evident that the biological properties of the different immunoglobulin preparations have to be considered for different therapeutic use. As some prophylactic and therapeutic indications are accepted, the benefit of immunoglobulin administration during sepsis still remains uncertain.

Bacterial Infections↗

[Granulocyte function in premature infants before the 34th week of pregnancy and in mature newborn infants].

BACKGROUND: Preterm and term neonates have an increased risk to develop severe bacterial infections. Impairment of neutrophil function may be responsible for this increased risk. Other diseases related to prematurity like retinopathia of prematurity (ROP) or broncho-pulmonary dysplasia (BPD) on the other hand may be due to poorly controlled O2-radical production. PATIENTS AND METHODS: Blood samples of 112 premature (34 weeks of gestation and older) and term neonates were analysed. Blood samples of 23 healthy adults (18 to 50 years old) served as controls. O2-radical production and phagocytosis of neutrophils were determined by flow cytometry, using a commercial test system. RESULTS: Under the experimental conditions applied, the capacity to produce O2-radicals following vigorous stimulation (E. coli) is comparable between neutrophils of preterm/term neonates and healthy adults. However, unstimulated or weakly stimulated (fMLP) neutrophils of preterm and term neonates show a statistically higher O2-radical production as neutrophils of the control group. The production of oxygen radicals increases during the first 10 days of the life. The capability of neutrophils to phagocytose E. coli is significantly lower in newborns (preterm and term) compared to the adult controls. CONCLUSIONS: The values reported here for phagocytosis and O2-radical production utilizing a commercially available test system may serve as "preliminary normal values" for neonates. No differences were found between the groups of neonates with and without infection. Impaired neutrophil-phagocytosis possibly contributes to the increased risk of preterm and term neonates to acquire bacterial infections. The increased spontaneous O2-radical production, on the other hand, may play a role for the development of so called "free radical diseases" such as ROP or BPD. However, our results cannot add further proof to this hypothesis.

Adult↗

[Measuring vibrations of transport stress in premature and newborn infants during incubator transport].

BACKGROUND: Despite increasing numbers of centers for perinatology, transportation of newborns and premature infants can not totally be avoided for several obvious reasons. The following investigations were carried out as part of our quality control measures of the established neonatal transportation system, and were aimed on the optimization of a new neonatal transportation equipment resulting in reduction of transportation stress caused by acceleration forces. METHOD: The new system investigated consisted of a Volkswagen type T4 equipped with a Dräger incubator type 5400, which was mounted on a pneumatic patient lift. We measured acceleration forces in three axes (expressed as K-Wert) as well as over a spectrum of frequencies (1-80 Hz). Measurements were taken at different points of the transportation unit during simulated transports driving a predetermined route. After obtaining informed consent of the parents, one actual transport of a newborn was used for an additional point measurement at the newborn's head. RESULTS: The mean K-Wert was decreased by about 50% in the vertical axis between the chassis of the car and the incubator by activating the pneumatic patient lift. Without activating the lift the K-Wert increased by about 20% between the car's chassis and the incubator. The frequency analysis showed resonance effects between the different components of the system. However, by activating the patient lift, effective accelerations in the incubator were decreased to less than 0.1 m/s2 across the whole frequency spectrum evaluated. The single measurement at a newborn's head revealed similar acceleration forces at the head of the baby and under its head. CONCLUSIONS: Utilization of a pneumatic patient lift can reduce acceleration forces. However, our results show that each system (car, incubator, and its base) has to be investigated and optimized for this purpose as a unit. Optimization of the complete system is necessary not only before its primary use but also in regular intervals over the years. Sometimes, further improvements can be reached with minor modifications such as the exchange of worn out rubber buffers.

Acceleration↗