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E J Rushing

Publications and source records attributed to E J Rushing.

At least 19 recordsLinked to original sources
PubMed2001

Ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain.

Neurofibromatosis type 1 (NF1) is a prevalent genetic disorder that affects growth properties of neural-crest-derived cell populations. In addition, approximately one-half of NF1 patients exhibit learning disabilities. To characterize NF1 function both in vitro and in vivo, we circumvent the embryonic lethality of NF1 null mouse embryos by generating a conditional mutation in the NF1 gene using Cre/loxP technology. Introduction of a Synapsin I promoter driven Cre transgenic mouse strain into the conditional NF1 background has ablated NF1 function in most differentiated neuronal populations. These mice have abnormal development of the cerebral cortex, which suggests that NF1 has an indispensable role in this aspect of CNS development. Furthermore, although they are tumor free, these mice display extensive astrogliosis in the absence of conspicuous neurodegeneration or microgliosis. These results indicate that NF1-deficient neurons are capable of inducing reactive astrogliosis via a non-cell autonomous mechanism.

Alleles↗
PubMed2001

Characterization of initiated cells in N-methylnitrosourea-induced carcinogenesis of the CNS in the adult rat.

Glial tumors may originate from the malignant transformation of multipotent glial progenitor cells, but tools to study malignant transformation leading to gliomas are limited by the lack of biological systems that represent early stages of this disease in adult animals. In order to characterize the initiated cells that give rise to gliomas, we have employed the N-methylnitrosourea (MNU) model for induction of brain tumors in adult rats (Rushing et al., 1998). Specifically, we have isolated and cultured transformed (premalignant) cells from normal-appearing brains of rats exposed to MNU for 10 weeks and from histologically abnormal brains of rats exposed to MNU for 15 weeks. We compared them with cells cultured from control animals under identical conditions. Cultured cells were classified according to their morphology, immunophenotype, karyotype, proliferation capacity, and tumorigenicity in athymic mice. Cultures from untreated normal rat brains grew as monolayers and had normal karyotypes (42 X,Y), epithelioid morphology, and slow proliferative capacity (doubling time > 120 h). In contrast, cultured cells from brains of MNU-exposed animals had karyotypes that ranged from normal to highly aneuploid. Aneuploid lines grew rapidly in multilayers (doubling time < 24 h), had differentiated astrocytic or oligodendroglial morphology and immunohistochemical staining profile, and yielded tumors in athymic mice. Initiated cells with minor chromosomal aberrations assumed mixed bipolar or tripolar morphologies in high density cultures, proliferated rapidly, but showed contact inhibition and failed to induce tumors when injected s.c. in athymic mice. In general, lines showing no evidence of chromosomal aberrations had the most epithelioid morphology, proliferated slowly (doubling time > 72 h), and retained strict contact growth inhibition. The presumed undifferentiated glial progenitor cells in culture from either control or MNU-treated rats variably expressed markers such as vimentin, nestin, and NG2 proteoglycan, and they weakly expressed the mature astrocytic or oligodendroglial markers glial fibrillary acidic protein or galactocerbroside, respectively. These cultures differentiated to bipolar-tripolar morphology with concomitant maturation to a GFAP+ or GalC+ phenotype upon exposure to secondary messengers such as dibutyryl-cyclic-AMP and/or growth factors such as basic fibrillary growth factor. Continuous stimulation with these messengers resulted in terminal differentiation and consequent death upon withdrawal of the stimulus. These results provide information that could lead to detailed characterization of initiated, premalignant cells in the adult brain and to a better understanding of glial carcinogenesis.

Animals↗
PubMed2001

Infections of the nervous system.

This article surveys common causes and pathologic features of nervous system infections within the general population. Special consideration is given to infections in people with the HIV virus.

AIDS-Related Opportunistic Infections↗
PubMed2000

Proliferative activity in craniopharyngiomas: clinicopathological correlations in adults and children.

BACKGROUND: Craniopharyngiomas are slow-growing, locally invasive intracranial tumors that can generate considerable morbidity, and recurrences are often difficult to manage. Because reliable morphologic criteria for accurately predicting the clinical outcome of these tumors are lacking, we evaluated the growth potential of craniopharyngiomas by measuring their proliferative activity based on MIB-1 immunostaining for the Ki-67 antigen, which is expressed during all phases of the cell cycle except G(0.) METHODS: Paraffin sections from 37 cases of craniopharyngiomas were immunostained with the monoclonal antibody MIB-1, and a labeling index was derived in each case from an the with the highest labeling. RESULTS: MIB-1 immunoreactivity was mainly confined to the peripheral palisaded epithelium of craniopharyngiomas. In adult craniopharyngiomas, MIB-1 labeling indices (MIB-LI) varied from 0.1% to 34.6% (mean 8.9%; SD 9. 8), and in pediatric tumors the indices ranged from 1.8% to 15.0% (mean 6.3%; SD 3.7). MIB-LI was not found to be an independent predictor of recurrence, although in all the pediatric cases that recurred, MIB-LI in the second specimen was greater. CONCLUSIONS: The actively proliferating compartment in craniopharyngiomas seems to be the peripheral palisaded epithelium. Low MIB-LI observed in the majority of tumors is in concordance with the slow growth and low-grade invasiveness associated with craniopharyngiomas. However, unlike other intracranial neoplasms, where Ki-67 labeling indices have been useful in predicting tumor behavior, a clear relationship could not be demonstrated between MIB-1 immunoreactivity, morphological features and clinical outcomes in adults or children with craniopharyngiomas.

Adolescent↗
PubMed2000

Alpha-synuclein expression in central nervous system tumors showing neuronal or mixed neuronal/glial differentiation.

Alpha-synuclein (alpha-synuclein) is a member of a family of cytoplasmic proteins found predominantly and abundantly in the brain, and concentrated in pre-synaptic nerve terminals, near vesicles. We hypothesized that an antibody to alpha-synuclein could be a useful marker of neuronal differentiation in central nervous system (CNS) tumors. Twenty tumors known to have neuronal or mixed neuronal/glial differentiation ( 11 gangliogliomas, 2 anaplastic gangliogliomas, 5 gangliocytomas, and 2 ganglioneuroblastomas), 5 central neurocytomas, and 1 dysembryoplastic neuroepithelial tumor (DNET) were immunostained with a mouse monoclonal antibody raised against human alpha-synuclein. Intense cytoplasmic staining, in some instances extending into the perikarya, was seen in 6 of 11 gangliogliomas, 2 of 2 anaplastic gangliogliomas, and 2 of 2 ganglioneuroblastomas. Alpha-synuclein-positive cells were usually large in size, resembled dysmorphic neurons, and were variably immunoreactive for anti-neurofilament and/or anti-synaptophysin antibodies. In contrast, central neurocytomas, gangliocytomas, and the DNET were negative for cytoplasmic alpha-synuclein expression. Our findings indicate that alpha-synuclein is expressed within the neuronal component of mixed tumors of the CNS displaying more than 1 histophenotype, and/or showing different degrees of anaplasia. Based on currently available data, we conclude that cytoplasmic alpha-synuclein expression is a marker of maturing neurons in these tumors.

Cell Differentiation↗
PubMed2000

Recurrent (nonfamilial) hemangioblastomas involving spinal nerve roots: case report.

OBJECTIVE AND IMPORTANCE: Spinal nerve root hemangioblastomas are rare and are reported mainly in patients with von Hippel-Lindau (VHL) syndrome. The pathogenesis of so-called nonfamilial lesions is virtually unknown. We discuss, mainly from a molecular perspective, a unique patient with sporadic, recurrent hemangioblastomas restricted to spinal nerve roots. CLINICAL PRESENTATION: A 53-year-old man who had had a surgically corrected lumbosacral meningomyelocele presented on at least three occasions during a 17-year period with multifocal capillary hemangioblastomas involving spinal nerve roots. On each occasion, tumors appeared on a different nerve root, with the majority located in the midcervical segments. The patient had no clinical features or family history of VHL syndrome. TECHNIQUE: To obtain a clearer understanding of the pathogenesis of this unusual case and its relationship to VHL syndrome, molecular analysis of the VHL gene was performed by use of complete sequence analysis and loss of heterozygosity studies on deoxyribonucleic acid derived from the patient's blood leukocytes and three separately resected hemangioblastomas. CONCLUSION: Germ-line molecular analysis performed on all three exons in the VHL gene coding region did not indicate that any mutations were present. Loss of heterozygosity analysis of deoxyribonucleic acid from the three hemangioblastoma resections showed normal heterozygosity in the 3p25-26 region. Complete VHL gene sequence analysis did not demonstrate a somatic mutation in the coding region of the VHL gene in any of the three tumors, thereby supporting the loss of heterozygosity data that a molecular event directly involving the VHL gene may not be the causative factor in their tumorigenesis.

Base Sequence↗
PubMed1999

Mouse tumor model for neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by increased incidence of benign and malignant tumors of neural crest origin. Mutations that activate the protooncogene ras, such as loss of Nf1, cooperate with inactivating mutations at the p53 tumor suppressor gene during malignant transformation. One hundred percent of mice harboring null Nf1 and p53 alleles in cis synergize to develop soft tissue sarcomas between 3 and 7 months of age. These sarcomas exhibit loss of heterozygosity at both gene loci and express phenotypic traits characteristic of neural crest derivatives and human NF1 malignancies.

Animals↗
PubMed1999

Multidisciplinary approach to traumatic intracranial aneurysms secondary to shotgun and handgun wounds.

BACKGROUND: Traumatic intracranial aneurysms (TICAs) may develop following gunshot injuries to the head. Management of these lesions often combines various aspects of microneurosurgical and endovascular techniques to safely repair or obliterate vessel defects. METHODS: We reviewed our experience over the last 18 years and identified five cases of intracranial aneurysms following gunshot and handgun wounds that were treated surgically and/or endovascularly. RESULTS: All patients had successful obliteration of their lesions using a variety of therapeutic modalities aimed at preserving neurologic function while at the same time eliminating the aneurysm from the circulation. CONCLUSION: Both microneurosurgery and endovascular surgery have important roles to play in the management of TICAs. In some cases, both methods can be combined to eliminate lesions and maximize patient recovery in a safe, efficient, and effective fashion.

Adult↗
PubMed1999

Radiation change versus recurrent astrocytoma: diagnostic utility of the proliferation index?

Differentiation of recurrent glioma from radiation damage can be a challenge to neurologists, neurosurgeons, neuroradiologists, and even neuropathologists. We hypothesized that by evaluating sections of recurrent lesions with proliferation markers we might objectively differentiate between radiation damage gliosis and recurrent astrocytoma. We compared the labeling indices of radiation damage and recurrent neoplasm immunohistochemically, using an antibody to MIB-1, a monoclonal antibody to the Ki-67 proliferation marker. Five of the six recurrent neoplasms were gliomas; four these were astrocytic tumors. In most cases, the MIB-1 LI of radiation damage was < 1% and the LI of recurrent neoplasm was > 3%, with pertinent exceptions. We discuss our findings and their possible interpretation.

Adult↗
PubMed1999

Prognostic value of proliferation index and expression of the RNA component of human telomerase (hTR) in papillary meningiomas.

Papillary meningioma is a rare subtype of meningioma that often behaves aggressively. In order to characterize factors that may influence this behavior, we chose to compare MIB-1 labeling index (LI) and telomerase RNA localization (hTR) in papillary meningiomas, meningiomas, and atypical meningiomas. LI is now often used to supplement histologic grade in the evaluation of these lesions. More recent studies indicate that increased expression of hTR is detected in many neoplastic cells, and may play an essential role in cell immortalization. The study group consisted of five papillary meningiomas (and a recurrence in one case), 11 conventional meningiomas, and eight atypical meningiomas. Conventional meningiomas showed either negative or 1 + hTR. Atypical meningiomas showed 1 + hTR. Papillary meningiomas showed the highest hTR (five of six, including recurrence, 2-3+ and one 1+). Generally, the LI was very low for conventional meningiomas (< 2%). The LI of atypical meningiomas ranged from 3-19%, mean 12%, and from 5.5-17.5%, mean 11.75% for papillary meningiomas. LI differentiated between meningiomas, and papillary or atypical meningiomas. hTR further delineated papillary (moderate to high) from atypical meningiomas (low). The combined variable of LI and hTR expression could be a useful independent prognostic indicator in patients with papillary meningioma.

Adolescent↗
PubMed1998

Glial tumors in the MNU rat model: induction of pure and mixed gliomas that do not require typical missense mutations of p53.

Gliomas were induced in adult male Sprague-Dawley rats by continuous exposure to 100 ppm of N-nitrosmethylurea (MNU) in drinking water. Latency periods for such tumors were 20 and 50 weeks following completion of exposure intervals of 20, 15, and 10 weeks, respectively. Based on histomorphology and the pattern of GFAP immunoreactivity, a large percentage of MNU-induced tumors (>40%) were anaplastic mixed gliomas, having both neoplastic astrocytic and oligodendroglial components. Typical oligodendrogliomas and astrocytomas also occurred less frequently. Unlike the majority of tumors induced by ethylnitrosourea (ENU), MNU yielded glial tumors that did not express synaptophysin. Anaplastic mixed gliomas and glioblastoma multiforme (GBMs) had no missense p53 mutations in the commonly mutated exons 4 through 8 and did not overexpress wild-type p53, suggesting that MNU-induced oncogenesis in rat brain tumors may not require inactivation/alteration of the p53 tumor suppressor gene. The K-ras gene was also analyzed and found to have no activating mutations in brain tumors. This model is suitable for studying genetic events leading to the majority of gliomas that apparently express functional p53.

Animals↗
PubMed1998

Hormone receptor immunoreactivity in hemangioblastomas and clear cell renal cell carcinomas.

Several primary central nervous system (CNS) neoplasms, including meningiomas, spinal cord ependymomas, and acoustic nerve schwannomas, express hormone receptors. In the present study, we investigated hormone receptor immunoreactivity in hemangioblastomas on the basis of recent reports of these tumors complicating pregnancy. We also evaluated cases of renal cell carcinoma (RCC) metastatic to the CNS, hypothesizing that estrogen receptor (ER), progesterone receptor (PR), or androgen receptor (AR) immunoreactivity might help to distinguish between these histologically similar neoplasms. Immunohistochemical analysis for ERs, PRs, and ARs was performed on paraffin-embedded sections of 27 hemangioblastomas, 12 primary clear cell RCCs, and 5 clear cell RCCs metastatic to the CNS. All of the hemangioblastomas demonstrated PR immunoreactivity, whereas 10 of 12 primary RCCs were negative. In addition, four of the five metastatic RCC were PR positive. All but one primary RCC were ER negative. AR immunoreactivity was seen in three hemangioblastomas, five primary RCCs, and one metastatic RCC. Although hormone receptor immunoreactivity was unable to distinguish between hemangioblastoma and clear cell RCC metastatic to the CNS, the identification of PR immunoreactivity in hemangioblastomas is a new finding that might have adjuvant therapy treatment implications.

Adolescent↗
PubMed1998

Supratentorial giant cell ependymoma: a case report.

Ependymomas are neoplasms of the central nervous system that are capable of demonstrating remarkably heterogeneous histologic features. These tumors originate from ependymal cells lining the ventricles, the choroid plexus, the central canal of the spinal cord, and the filum terminale, so they are therefore seen throughout the neuraxis. We describe the case of a 26-year-old man who experienced a 3-week history of right-sided numbness and a 1-week history of worsening bifrontal headache. Computed tomographic scanning and magnetic resonance imaging of his head demonstrated an irregularly enhancing mass involving the left medial frontal lobe, with extension across the corpus callosum and expansion into the body and atrium of the left lateral ventricle. Histologic, immunohistochemical, and electron microscopic findings were consistent with an anaplastic ependymoma. Unique to this neoplasm was the presence of multiple tumor giant cells. The presence of pleomorphic tumor giant cells is a characteristic feature of the subependymal giant cell astrocytoma, and it is also commonly seen in pleomorphic xanthoastrocytoma and glioblastoma multiforme. Bizarre giant cells were recently described in two filum terminale ependymomas. This report presents the first case of a supratentorial giant cell ependymoma with anaplastic features.

Adult↗
PubMed1998

Correlation of bcl-2, p53, and MIB-1 expression with ependymoma grade and subtype.

In this study, we report our results on the proliferative activity of ependymomas as determined by MIB-1 (also known as Ki-67) immunohistochemical analysis, and we compare our results with those obtained by immunolabeling with monoclonal antibodies to p53 and bcl-2 proteins to assess whether expression correlated with ependymoma subtype or tumor grade. The study included 4 myxopapillary ependymomas (Grade I of the World Health Organization [WHO] scale), 10 subependymomas (WHO Grade I), 17 ependymomas (WHO Grade II), 2 papillary ependymomas (WHO grade II), and 4 anaplastic ependymomas (WHO Grade III). The MIB-1 proliferation index was significantly higher in tumors diagnosed as anaplastic ependymoma (P < .001), with a moderate level of correlation (Kendall's tau-b = 0.557, asymptotic standard error = 108). In addition, one ependymoma (WHO Grade II) not considered overtly anaplastic by routine histologic criteria showed a high MIB-1 labeling index, suggesting that the MIB-1 proliferation index might be a more objective indicator of tumor grade. The remaining WHO Grade I and Grade II ependymomas showed low proliferative activity. bcl-2 oncoprotein expression was identified in all of the four myxopapillary and in both papillary ependymomas. An additional observation was the correlation of p53 expression with increasing WHO grade. These data suggest that high MIB-1 and p53 immunolabeling might be objective indicators of high grade in ependymomas that do not otherwise meet routine histologic criteria for high-grade ependymoma. Subsequent clinicopathologic analyses will be important in assessing whether these markers are useful as independent predictors of survival.

Adolescent↗
PubMed1998

Bad news and good news: what the dentist needs to know about transmissible spongiform encephalopathies.

Since reports of the "mad cow disease" epidemic in Great Britain erupted in the international press, sensational and intimidating articles about the risk that bovine spongiform encephalopathy and related diseases may pose to humans have appeared. The bad news is that compelling scientific evidence suggests so-called prion disease can and has infected humans, although the overall risk appears to be low. Furthermore, at present, there is no reliable antemortem diagnosis, specific treatment, or vaccine to prevent the disease. The agent thought to be responsible for this unusual class of disease is a rogue protein (called a prion) that, unlike all other agents known to cause infectious disease, contains neither DNA nor RNA. According to a popular hypothesis, normal membrane-associated prion proteins undergo conformational changes that can cause disease. The "bad" prion forms cause holes or a spongy appearance in the brain in all disease variants, hence the generic designation of spongiform encephalopathy. The good news is that risk for exposure to prion disease is exceedingly remote in the dental practice and that current universal infection control procedures are probably sufficient.

Animals↗
PubMed1997

Nonneoplastic pineal cysts: a clinicopathologic study of twenty-one cases.

Twenty-one cases of nonneoplastic pineal cyst are presented. The patients were 13 women and 8 men, with a median age of 33 years. Sixteen patients were symptomatic. Symptomatic cysts had an average size of 16.5 mm. In most cases, symptoms and signs were related to increased intracranial pressure, cerebrospinal fluid obstruction, neuroophthalmologic dysfunction, brainstem and cerebellar compression, and mental status changes. Uncommon clinical presentations in three cases were related to increased cyst size caused by hemorrhage, sudden death, and postural syncope and loss of consciousness. Imaging studies showed a uniform hypodense or hypointense, nonenhancing pineal mass with occasional peripheral calcification and associated with hydrocephalus, aqueductal compression, tectal deformity, and hemorrhage within the cavity, in decreasing order of frequency. Fourteen patients underwent open cyst resection. Histologically, the intact lesions show a unilocular or multilocular cavity, surrounded by a wall comprised of variable amounts of glial tissue, remnants of pineal gland, and an external fibrous capsule. Follow-up information showed 12 patients alive and well without recurrence between 26 and 144 postoperative months. One patient who underwent stereotactic drainage had a recurrence. One symptomatic patient who did not have surgery died suddenly of causes related to the cyst. The present study supports the role of surgical excision for the treatment of symptomatic pineal cysts to obtain adequate tissue for diagnosis and relief of symptoms. The use of histochemical and immunohistochemical studies may prove useful in the distinction of these lesions with astrocytomas and cystic pineal parenchymal tumors.

Adolescent↗