Serious infection due to Borrelia burgdorferi and the disseminated infection characteristic of the disease possess unique treatment problems. The wide and still increasing incidence of Lyme borreliosis as well as the problems in treatment call for effective prevention strategies by active immunization. Vaccination experiments were done to determine if active immunization of gerbils with recombinant OspA and pC protects against infection with strains of B. burgdorferi. Gerbils were vaccinated with recombinant OspA and pC (20 kDa protein) and challenged four weeks later with a clone (derived from B. burgdorferi strain PKo) which expresses an abundant amount of pC but only little OspA. Non-immunized gerbils challenged with the same B. burgdorferi strain were used as controls. Both groups of immunized gerbils developed antibodies against the recombinant vaccines. The pC vaccinated group was protected against infection, whereas the OspA vaccinated group showed signs of infection. The non-vaccinated group developed generalised infection. These results show that pC should be considered as a further vaccine candidate and probably needs to be combined with OspA for an efficient vaccine against B. burgdorferi.
The number of spines along the apical dendrites of the pyramidal neurons in the hippocampal and cingulate gyri were counted on Golgi preparations of the brains of seven cases of Down's syndrome; they did not show neuropathological senile changes. The number of spines in the middle and distal segments of the apical dendrites of Down's syndrome group were significantly fewer than in those of the control group. The number of spines in aged noncharacteristic mentally retarded cases were not decreaed compared with the controls. The diminution of spines in Down's syndrome is considered to be rather specific in this condition and is not a common finding in other types of mental retardation. It might also be one of the early changes of dendritic degeneration related to senile plaque formation.
BACKGROUNDTenascin‐C (TN‐C), a large extracellular matrix (ECM) glycoprotein with a molecular weight of 180–250 kilodaltons, is present in several normal adult tissues. TN‐C is up‐regulated during embryogenesis, in wound healing, and in tumor tissues. Glioblastoma multiforme (GBM) is the most frequent and malignant astrocytic tumor comprised of poorly differentiated, neoplastic astrocytes. Recently, TN‐C‐based radioimmunotherapy was administered to patients with GBM.METHODSIn the current study, the authors used immunohistochemistry to conduct a systematic investigation of TN‐C distribution patterns in normal human brain tissue and in a large variety of brain tumors (n = 485 tumors). Immunoreactivity for TN‐C was assessed with regard to its localization within tumor cells, blood vessels, and ECM using three different monoclonal antibodies (clones BC2, BC4, and TN2).RESULTSIn control human brains, a significant difference was noted in the expression of TN‐C when comparing gray with white matter using either Western blot analysis or immunohistochemistry. TN‐C was found in the white matter of the frontal, temporal, parietal, and occipital lobes and in the hippocampus, where the immunoreaction was especially strong in the hippocampal formation. In 181 astrocytomas of different grades (World Health Organization [WHO] Grade 2–4), TN‐C immunopositivity was seen to varying degrees in the cellular and stromal components of the tumor and in tumor‐associated vessels. Glioblastomas (n = 113 tumors) showed strong immunopositivity in the vessels and moderate immunopositivity of the ECM. A statistically significant reduction of TN‐C immunopositivity in tumor‐associated vessels or ECM was observed in anaplastic astrocytomas (WHO Grade 3) compared with GBM (WHO Grade 4). A Kaplan–Meier analysis showed that patients who had GBM lesions that lacked TN‐C immunopositivity in the ECM had a significantly longer survival (median, 28 months; standard error, 7.8 months) (n = 12 patients) compared with patients who had GBM lesions with TN‐C immunopositivity (median, 12 months; standard error, 1.6 months) (n = 87 patients). In meningiomas (n = 24 tumors), the neoplastic cells, the ECM of the tumor, and the vessels were TN‐C negative. In schwannomas (n = 31 tumors), the tumor cells were TN‐C negative; whereas, in > 50% of tumors, the vessels and the ECM of regressively altered tumor areas were positive. In metastatic carcinomas (n = 53 tumors), the tumor cells were negative; seldom were vessels stained positive for TN‐C. Focal areas of the ECM, often accompanied with fibrotic changes, were immunopositive for TN‐C.CONCLUSIONSThe most constant TN‐C immunopositivity was noted in the ECM of the fibrotic stroma in highly malignant brain tumors and along the tumor border, especially in high‐grade astrocytomas. The current results suggest that TN‐C expression may be correlated with the grade of malignancy in astrocytic tumors and that the presence or absence of TN‐C expression in the stroma of astrocytic tumors may play a not yet clearly understood role in shortening or prolonging, respectively, the survival of patients. Cancer 2003. © 2003 American Cancer Society.
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