BACKGROUND: Stem cells, having the property of self renewal, offer the promise of lifelong repair of damaged tissue. However, somatic tissue-committed primary stem cells are rare and difficult to expand in vitro. Genetically modified stem-like cells with the ability to expand conditionally provide a valuable tool with which to study stem cell biology, especially the cellular events of proliferation and differentiation. In addition, stem cells may be appropriate candidates for therapeutic applications. METHODS: Double transgenic mice possesing SV40 T antigen (Tag) under the control of the reverse tetracycline-transactivator (rtTA) were used to establish cell lines. One brain cell line was partially characterized by DNA sequencing, morphology, antigen expression using flow cytometry, confocal microscopy, and electrophysiology using the patch clamp technique. Cell cycle analysis was performed using propidium iodide staining; cell viability and H3-thymidine incorporation assays. The ability of this cell line to differentiate was assessed by confocal microscopy following co-culture with stem cells secreting cytokines. RESULTS: We report here the establishment and partial characterization of a cell line derived from the brain tissue of rtTA-SV40 Tag transgenic mice. Analysis of the morphology and antigen markers has shown that this cell line mimics some aspects of primary glial precursors. The results of electrophysiology are consistent with this and suggest that the cell line is derived from O2A glial precursor cells. Cell cycle progression of this cell line is doxycycline-dependent. In the absence of doxycycline, cells become apoptotic. Differentiation into mature type 2 astrocytes and (precursor) oligodendrocytes can be induced upon withdrawal of doxycycline and addition of epithelial stem cells secreting cytokine, such as hIL3 (human Interleukine 3) or hIL6 to the culture. In contrast, co-culturing with hCNTF (human Ciliary NeuroTrophic Factor)-secreting epithelial stem cells did not induce them to mature into progeny cell types. CONCLUSION: The differentiation of this O2A glial precursor line does not occur automatically in culture. Additional external help is required from the cell-based delivery of appropriate transgenic cytokines. Withdrawal of doxycycline from the culture medium removes the proliferation signals and induces a fatal outcome.

Animals↗

PubMedDate not supplied

Computerized management of patient care in a complex, controlled clinical trial in the intensive care unit.

Acute respiratory distress syndrome (ARDS) is often not responsive to conventional supportive therapy and the mortality rate may exceed 90%. A new form of supportive care, extracorporeal carbon dioxide removal (ECCO2R), has shown a dramatic increase in survival (48%). A controlled clinical trial of the new ECCO2R therapy versus conventional continuous positive pressure ventilation (CPPV) is being initiated. Detailed care protocols have been developed by 'expert' critical care physicians for the management of patients. Using a blackboard control architecture, the protocols have been implemented on an existing hospital information system and will direct patient care and help manage the controlled clinical trial. Therapeutic instructions are automatically generated by the computer from data input by physicians, nurses, respiratory therapists, and the laboratory. Preliminary results show that the computerized protocol system can direct therapy for acutely ill patients.

Blood Gas Analysis↗

PubMedDate not supplied

Microwave-induced hyperthermia in cancer treatment: apparatus and preliminary results.

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Adenocarcinoma↗

PubMedDate not supplied

Reconstruction of the valgus-impacted humeral head fracture.

Between 1985 and 1991, 22 patients (average age 52 years, range 26 to 65 years) with severely impacted humeral head fractures were operated on with the aim of preserving the humeral head. All 22 cases showed no significant lateral displacement. Thus it was assumed that the periosteum leading medially to the humeral head was intact and that the vessels passing through the periosteum would ensure survival of the humeral head segment. All patients underwent treatment with open reduction. The impacted segment of the humeral head was raised, the tuberosities were relocated, and the void was filled with chips of cancellous bone. This procedure provided fixation with minimal osteosynthesis. At follow-up evaluation (minimum 18 months, average 36 months) one patient had sequestration of the head segment, and another patient had clinically asymptomatic partial necrosis. None of the remaining 20 patients showed signs of necrosis. Slight arthrosis was present in two patients, and moderate arthrosis was present in one. A correlation was found between the functional result and the quality of reduction. Where anatomic reconstruction had been successful, the long-term functional result was almost identical with the nontraumatized side.

Adult↗