Papers by Lauren Langford
Advances in Stereotactic and Functional Neurosurgery 10, 1993
The experiences with stereotactic biopsies in 121 patients with AIDS compared to 142 non-AIDS pat... more The experiences with stereotactic biopsies in 121 patients with AIDS compared to 142 non-AIDS patients are presented. In the AIDS group most of the tumors (38) were lymphomas (34). Other frequent diagnoses have been progressive multifocalleukencephalopathy (20) and toxoplasmosis (16)-although most AIDS patients already had been treated for toxoplasmosis, and those who responded to it did not undergo biopsy. Initially among the AIDS patients there was a tendency of delayed intracranial bleeding (4 cases, 3 of them fatal). After initiation of a prophylactic coagulopathy protocol no other such complications have occurred in the following 70 biopsies.
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, 1995
The WAF1/Cip1 protein is an important regulator at the G1 checkpoint in the cell cycle. The WAF1/... more The WAF1/Cip1 protein is an important regulator at the G1 checkpoint in the cell cycle. The WAF1/Cip1 protein binds to the cyclin-dependent kinase complexes and inhibits the kinase activity that is required for cell cycle progression. We investigated the expression of WAF1/Cip1 protein in 14 glioblastoma cell lines and found that WAF1/Cip1 expression was detectable in many of the cell lines, even when mutant p53 was present. We also showed that WAF1/Cip1 protein level was very low in LN-Z308 cells that do not express endogenous p53. Transfection of the wild-type p53 into this cell line activated WAF1/Cip1 expression and inhibited cell growth. In contrast, transfection of the p53 mutant 248Trp failed to activate WAF1/Cip1 expression. Transfection of WAF1/Cip1 alone also inhibited LN-Z308 cell proliferation. However, cotransfection of the p53 mutant 248Trp with WAF1/Cip1 attenuated the growth-suppression effect of WAF1/Cip1. Our analysis with Western blot showed that the levels of cyc...
Spine, 1990
Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic respo... more Magnetic resonance imaging (MRI) provides a noninvasive method of monitoring the pathologic response to spinal cord injury. Specific MR signal intensity patterns appear to correlate with degrees of improvement in the neurologic status in spinal cord injury patients. Histologic correlation of two types of MR signal intensity patterns are confirmed in the current study using a rat animal model. Adult male Sprague-Dawley rats underwent spinal cord trauma at the midthoracic level using a weight-dropping technique. After laminectomy, 5- and 10-gm brass weights were dropped from designated heights onto a 0.1-gm impounder placed on the exposed dura. Animals allowed to regain consciousness demonstrated variable recovery of hind limb paraplegia. Magnetic resonance images were obtained from 2 hours to 1 week after injury using a 2-tesla MRI/spectrometer. Sacrifice under anesthesia was performed by perfusive fixation; spinal columns were excised en bloc, embedded, sectioned, and observed with the compound light microscope. Magnetic resonance axial images obtained during the time sequence after injury demonstrate a distinct correlation between MR signal intensity patterns and the histologic appearance of the spinal cord. Magnetic resonance imaging delineates the pathologic processes resulting from acute spinal cord injury and can be used to differentiate the type of injury and prognosis.
Archives of pathology & laboratory medicine, 2004
Resorbable substances used to achieve hemostasis during neurosurgical procedures comprise 3 princ... more Resorbable substances used to achieve hemostasis during neurosurgical procedures comprise 3 principal classes based on chemical composition: (1) gelatin sponge, (2) oxidized cellulose, and (3) microfibrillar collagen. Nonresorbable hemostatic aides include various forms of cotton and rayon-based hemostats (cottonoids and kites). Resorbable and nonresorbable hemostatic agents have been reported to cause symptomatic mass lesions, most commonly following intra-abdominal surgery. Histologic examination typically shows a core of degenerating hemostatic agent surrounded by an inflammatory reaction. Each agent exhibits distinctive morphologic features that often permit specific identification. Hemostat-associated mass lesions have been variously referred to as textilomas, gossypibomas, gauzomas, or muslinomas. The aims of this study were to (1) identify cases of histologically proven cases of textiloma in neurosurgical operations, (2) characterize the specific hemostatic agent associated w...
Brain tumor pathology, 2012
Angiocentric glioma (AG) has been formally codified in the revised 2007 WHO Classification of Tum... more Angiocentric glioma (AG) has been formally codified in the revised 2007 WHO Classification of Tumours of the Central Nervous System. AGs characteristically exhibit mixed features of ependymal and diffuse astrocytic differentiation and low proliferation rates, with Ki-67 labeling indices ranging from less than 1 to 5%. A single case with anaplastic recurrence and a labeling index of 10% has been reported. In the present study, we report a series of three AGs (Case 1: 4-year-old girl at right frontal lobe; Case 2: 4-year-old boy at left frontal lobe; Case 3: 9-year-old boy at right temporal lobe). Case 1 with elevated proliferation index (~10%) and increased mitotic activity (six mitoses per 10 high-power fields) on phospho-histone H3 (pHH3) immunostain at presentation, nonetheless, has shown protracted recurrence-free survival after 6 years of follow-up. So far, this is the first report for evaluating the mitotic activity in AGs using pHH3 immunostain.
Endocrine, 1998
ATP-sensitive K+ (K ATP) channels modulated by sulfonylurea compounds have been previously identi... more ATP-sensitive K+ (K ATP) channels modulated by sulfonylurea compounds have been previously identified in the anterior pituitary of the rat and have been demonstrated to influence GH release. Recently, a sulfonylurea receptor (SUR) has been cloned from an islet cell tumor and identified as a member of the ATP binding cassette superfamily capable of coupling with inwardly rectifying potassium channels. To determine if the same receptor is expressed in pituitary tumors, SUR mRNA levels were measured in 28 human macroadenoma specimens using an RNase protection assay. All immunonegative, corticotrophin (ACTH), growth hormone (GH), and GH/prolactin (GH/Prl) immunostaining tumors expressed detectable amounts of SUR message. Among these tumors, only the GH and GH/Prl adenomas were functional. Of the tumors immunostaining for luteinizing hormone (LH), follicle-stimulating hormone (FSH), or both, SUR mRNA was present in small amounts in 5/11. Only 1/3 Prl immunostaining tumors contained SUR mRNA. In summary, we have demonstrated that SUR mRNA expression is common in several types of silent pituitary adenomas and in functional tumors that secrete GH. Lower levels are seen in some gonadotrophin immunostaining tumors.
Human Pathology, 1997
Telomerase, the enzyme that stabilizes telomere length, is reactivated with almost all cancer typ... more Telomerase, the enzyme that stabilizes telomere length, is reactivated with almost all cancer types, and it may be necessary for unlimited cell proliferation. Assessment of malignancy in ordinary meningiomas is inconclusive because no clear-cut correlation exists between aggressive clinical behavior and histological features or karyotypic abnormalities. We analyzed telomerase activity in 52 cases of meningioma by using the highly sensitive telomeric repeat amplification protocol and then compared clinical behavior in telomerase-positive and -negative ordinary meningiomas. Twenty-six of the 52 tumors (50%) had detectable telomerase activity. Twenty-one of the 22 neoplasms classified as malignant or atypical (95%) had detectable telomerase activity, and these tumors generally had a poor outcome. Interestingly, 5 of 30 ordinary (morphologically benign) meningiomas (17%) also showed detectable telomerase activity. Of the 5 patients with telomerase-positive ordinary meningiomas, 3 had rapid regrowth of the tumor despite gross total resection. The remaining 2 patients also had other primary malignancies. We observed a highly significant correlation in ordinary meningiomas between the presence of telomerase activity and a poor prognosis for the patient (P = .0002). Telomerase activity in benign meningiomas is clinically relevant because the presence of the enzyme suggests that these benign-appearing tumors may contain a population of immortal cells. The detection of telomerase activity may help to identify benign meningiomas that would be more likely to continue to grow and to recur clinically if surgical resection were incomplete.
The Lancet, 1995
Clinical investigation of gut immune responses: review on non-parenteral vaccines. Advanced Drug ... more Clinical investigation of gut immune responses: review on non-parenteral vaccines. Advanced Drug Delivery (in press). 5 Brydon WG, Ferguson A. Haemoglobin in gut lavage fluid as a measure of gastro-intestinal blood loss. Lancet 1992; 340: 1381-82. 6 Brydon WG, Choudari CP, Ferguson A. Relative specificity for active inflammatory bowel disease of plasma-derived proteins in gut lavage fluid.
Child's Nervous System, 2014
Introduction Juvenile xanthogranuloma (JXG) is a histiocytic condition in the spectrum of non-Lan... more Introduction Juvenile xanthogranuloma (JXG) is a histiocytic condition in the spectrum of non-Langerhans histiocytosis that preferentially affects children. Rarely this condition can involve the central nervous system (CNS) with devastating consequences. Methods The authors report the unique case of an 11-year-old child who initially presented with a sellar lesion without evidence of the cutaneous stigmata typical of JXG. She was later discovered to have JXG following initial diagnosis of granulomatous hypophysitis, with development of widespread intracranial disease and subsequent neurological deterioration. She underwent subtotal resection of her sellar lesion followed by whole brain radiation and systemic chemotherapy; however, she succumbed to her disseminated disease within 1 month of the JXG diagnosis. Conclusions This is a rare case of fatal disseminated intracranial JXG without cutaneous manifestations. Additionally, the initial presentation as a sellar lesion is particularly unusual and seldom described in the literature.
Neuro-Oncology, 2010
BACKGROUND: We demonstrated that GBM patients' T cells expressing HER2-specific chimeric antigen ... more BACKGROUND: We demonstrated that GBM patients' T cells expressing HER2-specific chimeric antigen receptors (CAR) killed autologous HER2 + GBM cells and induced regression of autologous xenografts; however, tumors recurred in a number of treated animals, likely due to limited T-cell persistence and/or tumor antigen loss variants. Since the majority of GBMs express CMVpp65, we expressed HER2.CARs in CMV-specific cytotoxic T cells (CTLs) to enhance their persistence following native T-cell receptor (alphabetaTCR) engagement with CMV-antigens and improve their antitumor activity by simultaneously targeting CMV and HER2. METHODS: To study the feasibility of generating CMV CTLs from GBM patients, we determined the precursor frequency of CMV-specific T cells in 25 patients using IFN-gamma-ELIspot assays. To generate CMV CTL, blood mononuclear cells were transduced with an adenovirus vector, encoding the immunodominant CMV-pp65 antigen (Ad5f35pp65) and then stimulated with autologous EBV-transformed Ad5f35pp65-transduced irradiated lymphoblastic cell lines (EBV-LCL). CTLs were then transduced with a retroviral vector encoding a HER2.CAR. We detected the expression of the CAR using flow cytometry. To concomitantly identify the CMV-specific T cell population, we used pentamers for CMVpp65 and performed 51 Cr-release assays to test their functionality. RESULTS: CMV-specific T cells were readily detectable in the blood of GBM patients, as judged by IFN-gamma secretion after stimulation with CMVpp65-PepMixes TM. We were able to generate CTLs that are specific for CMV through their endogenous alphabetaTCR and specific for HER2 through CAR. Approximately 50% of CMVpp65.CTLs expressed HER2.CARs on the cell surface. CMV.HER2.CAR CTLs recognized and killed the HER2+GBM cells as well as autologous T cells pulsed with CMVpp65-PepMixes TM in 51 Cr-release assays. Neither the HER2 cell lines nor autologous T cells were killed. CONCLUSION: Our data demonstrate the feasibility of generating CAR-expressing CMVpp65specific CTLs that are functional against HER2 and CMV expressed in GBM.
Journal of Neuro-Oncology, 1996
Ganglioglioma is an uncommon brain tumor with glial and neuronal cellular components and a somewh... more Ganglioglioma is an uncommon brain tumor with glial and neuronal cellular components and a somewhat benign course. We are presenting an unusual case of ganglioglioma with malignant transformation in both cellular components associated with an aggressive clinical course. An almost complete resolution of the recurrent progressing tumor was achieved after treatment with cis-retinoic acid (cRA) as a single agent. A possible differential effect of cRA on the neuronal component of the tumor is suggested.
Journal of Medical Primatology, 2001
The right cerebral hemisphere of 24 rhesus monkeys scheduled for necropsy at the completion of an... more The right cerebral hemisphere of 24 rhesus monkeys scheduled for necropsy at the completion of another project were studied histopathologically 1-30 days after a single dose of 60 Co-irradiation. Histopathologically, inflammation and gliosis consistently occurred at specific time points but varied in severity between individuals. Multifocal hemorrhage, edema, and an acute neutrophilic inflammatory response were observed initially whereas perivascular accumulations of lymphocytes were observed in specimens at the end of the study. Microglia/macrophages were most prominent during the first week after irradiation, whereas astrocytes were reactive throughout the observation period. The early clinical manifestations of the central nervous system (CNS), because of brain irradiation in humans, correspond temporally with acute vascular responses, acute and subacute inflammatory cell responses, and subacute demyelination and reactive astrocytic and microglial responses observed in the rhesus monkey. Initial responses of the CNS to gamma-irradiation may have potential implications for the development of radiation-induced late injury of the CNS.
Cancer, 1997
BACKGROUND During the course of their neuropathology practice, the authors received cases to revi... more BACKGROUND During the course of their neuropathology practice, the authors received cases to review in consultation. In some cases, the patients came to the authors' hospital for therapy; in others, the primary pathologists requested a consultation. Because changes in ...
Human Pathology, 1996
Meningiomas from 40 adult patients were labeled immunohistochemically with monoclonal antibodies ... more Meningiomas from 40 adult patients were labeled immunohistochemically with monoclonal antibodies to bromodeoxyuridine (BUdR) and the Ki-67 antigen, M1D1. The meningiomas were classified as classical, or benign (n = 31); atypical (n = 4); or malignant (n = 5). Meningeal sarcomas and hemangiopericytomas were excluded. The patient population consisted of 26 women and 14 men, ranging in age from 26 to 75 years. BUdR proliferation indices ranged from 0% to 5.8%, measurements that were expectedly lower than those for MIB-1, which ranged from 1.5% to 19.3%. M1B-1 proliferation indices were not significantly affected regarding steroid pretreatmerit or age. These results show a good correlation between the BUdR and MIB-I proliferation markers (rs = 0.72; P < .0001), which supports the use of anti-MIB-I as an alternative labeling tool to BUdR for the determination of the proliferation index in meningiomas, thus avoiding the admires" U'ation of a potentially mutagenic drug. HUM PATHOL 27:350-354.
Cancer research, Jan 15, 1999
MMAC/PTEN, a tumor suppressor gene located on chromosome 10q, has recently been shown to act as a... more MMAC/PTEN, a tumor suppressor gene located on chromosome 10q, has recently been shown to act as a phosphatidylinositol 3,4,5-triphosphate phosphatase and to modulate cell growth and apoptosis. Somatic mutations of MMAC/PTEN have been reported in a number of human cancers, especially in glioblastoma multiforme (GBM), although the number of identified mutations (approximately 10-35%) is significantly lower than the frequency of LOH affecting the MMAC/PTEN locus in the specimens (approximately 75-95%). To further investigate the possible alterations that may affect MMAC/PTEN, we examined the expression of the gene by reverse transcription-PCR in a series of gliomas. A significant difference (P < 0.001) was observed between the expression of MMAC/PTEN in GBMs versus lower grades of gliomas, thus mimicking the difference in allelic deletion associated with the locus in these tumors. Furthermore, Kaplan-Meier survival plots, adjusted for age and tumor grade, showed a significantly bett...
Cancer research, 1997
A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recent... more A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and ...
Neurosurgery, 2007
OBJECTIVE The pineal region is a rare intracranial site for metastasis. We report three patients ... more OBJECTIVE The pineal region is a rare intracranial site for metastasis. We report three patients initially considered to have metastatic papillary adenocarcinoma to the pineal region. On review, these papillary, keratin-positive neoplasms meet the criteria for papillary tumor of the pineal region (PTPR). CLINICAL PRESENTATION These neoplasms occurred in three women (age range, 37–55 yr). Imaging studies demonstrated well-circumscribed lesions in the pineal region. All patients presented with obstructive hydrocephalus and symptoms attributable to hydrocephalus and tectal compression. INTERVENTION All three patients underwent near total microsurgical resection of the pineal region neoplasm, followed by adjuvant radiotherapy. The two patients with long-term follow-up (56–60 mo) have remained clinically stable without evidence of local or distant recurrence. The first two patients were initially diagnosed as having papillary metastatic carcinoma of unknown origin. The third patient was ...
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Papers by Lauren Langford