PubMed Health⌕ Search

Biomedical subjects

Thomas J Cummings

Publications and source records attributed to Thomas J Cummings.

At least 19 recordsLinked to original sources
PubMed2006

Systemic anti-CD25 monoclonal antibody administration safely enhances immunity in murine glioma without eliminating regulatory T cells.

PURPOSE: Elevated proportions of regulatory T cells (T(reg)) are present in patients with a variety of cancers, including malignant glioma, yet recapitulative murine models are wanting. We therefore examined T(regs) in mice bearing malignant glioma and evaluated anti-CD25 as an immunotherapeutic adjunct. EXPERIMENTAL DESIGN: CD4+CD25+Foxp3+GITR+ T(regs) were quantified in the peripheral blood, spleens, cervical lymph nodes, and bone marrow of mice bearing malignant glioma. The capacities for systemic anti-CD25 therapy to deplete T(regs), enhance lymphocyte function, and generate antiglioma CTL responses were assessed. Lastly, survival and experimental allergic encephalitis risks were evaluated when anti-CD25 was combined with a dendritic cell-based immunization targeting shared tumor and central nervous system antigens. RESULTS: Similar to patients with malignant glioma, glioma-bearing mice show a CD4 lymphopenia. Additionally, CD4+CD25+Foxp3+GITR+ T(regs) represent an increased fraction of the remaining peripheral blood CD4+ T cells, despite themselves being reduced in number. Similar trends are observed in cervical lymph node and spleen, but not in bone marrow. Systemic anti-CD25 administration hinders detection of CD25+ cells but fails to completely eliminate T(regs), reducing their number only moderately, yet eliminating their suppressive function. This elimination of T(reg) function permits enhanced lymphocyte proliferative and IFN-gamma responses and up to 80% specific lysis of glioma cell targets in vitro. When combined with dendritic cell immunization, anti-CD25 elicits tumor rejection in 100% of challenged mice without precipitating experimental allergic encephalitis. CONCLUSIONS: Systemic anti-CD25 administration does not entirely eliminate T(regs) but does prevent T(reg) function. This leads to safe enhancement of tumor immunity in a murine glioma model that recapitulates the tumor-induced changes to the CD4 and T(reg) compartments seen in patients with malignant glioma.

Animals↗
PubMed2006

Complex choristoma of the gyrus rectus: a distinct clinicopathologic entity?

We report 2 cases of an unusual central nervous system lesion involving the gyrus rectus and characterized by well-differentiated epithelial and mesenchymal components. One patient was a 30-year-old woman, and the other was a 42-year-old man. Both presented with seizures. Radiologically, the lesions were solid, with ill-defined margins and increased signal on T2-weighted MRI. Both were contrast enhancing. There was no significant mass effect or edema. Histopathologically, the epithelial component was characterized by a tubule-forming, stratified epithelium. The lumina of the tubules were lined, in some areas, by a distinct layer of mature keratinocytes. Smooth muscle actin-immunoreactive myoepithelial cells were present in the basal layer, indicating glandular differentiation. Some lumina were cystically dilated and contained anucleate squames and/or PAS-positive material. In some areas, the epithelial structures were separated by reactive glial tissue resembling pilocytic astrocytoma, with prominent, piloid processes, Rosenthal fibers, and gemistocytic astrocytes. In other areas, glial nuclei formed small clusters reminiscent of subependymoma, but no glioma was identified in either case. Tissue resembling mature adipose was present focally. No mitotic figures were identified. Follow-up interval of up to 2 years showed no evidence of recurrent tumor. By location and histologic features, this lesion appears to represent a rare, distinct clinicopathologic entity, perhaps derived from misplaced cranial neural crest cells.

Adult↗
PubMed2006

Behavioural testing and histological assessments of rabbit spinal cord following intrathecal administration of ondansetron.

1. Intrathecal injection of ondansetron has the potential to reduce opioid-related side-effects. The aim of the present study was to determine whether this route of administration produces neuraxial injury. 2. Adult, non-pregnant female New Zealand white rabbits received a single bolus injection of a low (40 microg) or high (4.0 mg) dose of ondansetron into the intrathecal space between the 4th and 5th lumbar vertebrae. In some cases, ondansetron was coadministered with morphine (5 microg/kg). Control animals received a bolus injection of normal saline. Behavioural assessments were conducted at 1 and 24 h to determine overt changes in arousal and mobility, followed by histological evaluation of the excised spinal cord. 3. Of 45 animals investigated, 10 rabbits exhibited modest behavioural evidence of spinal injury, the incidence of which was equally distributed between the treatment groups. Haematoxylin and eosin, along with HAM56, staining of cross-sections of the cervical, thoracic and upper and lower lumbar areas revealed mild signs of inflammation. This, too, was equally distributed between the treatment groups, suggesting that any observed neuraxial injury was the result of needle trauma and not ondansetron neurotoxicity. 4. Collectively, these negative findings support conducting further experiments to fully assess the clinical usefulness of intrathecal ondansetron administration.

Animals↗
PubMed2006

Primary spinal intramedullary adrenal cortical adenoma associated with spinal dysraphism: case report.

OBJECTIVE: The authors report a primary spinal intramedullary adrenal cortical adenoma in a patient with spinal dysraphism presenting with bilateral leg pain and urinary frequency. METHODS: Magnetic resonance imaging, L2 laminectomy with resection of mass, and pathological and immunohistochemical analysis of resected mass revealed the diagnosis. RESULTS: Microscopic and immunohistochemical findings confirmed the diagnosis as a primary intramedullary tumor of adrenal cortical origin. CONCLUSION: The occurrence of a primary adrenal tumor in the spinal cord is rare and difficult to explain based on our understanding of embryology. A review of the relevant literature and discussion of the pathophysiology and clinical implications is provided.

Adrenal Cortex Neoplasms↗
PubMed2006

Primary myxoma of the parafalcine meninges. Case report.

The authors report on an unusual case of a primary intracranial myxoma in a 39-year-old woman. The patient presented with headache and generalized seizure. Magnetic resonance imaging revealed a large right frontal tumor resembling a parasagittal meningioma. A gross-total resection was performed, and histological review confirmed the lesion as a myxoma. Results of additional workup revealed the absence of a primary myxoma elsewhere. This case represents the third published report of a primary intracranial myxoma and the second report of a supratentorial myxoma.

Adult↗
PubMed2006

Capillary hemangioma of the fourth ventricle in an infant. Case report and review of the literature.

A 3-month-old boy presented to the pediatric neurosurgery service with central hypotonia. Magnetic resonance images of the brain revealed a homogeneously enhancing dumbbell-shaped mass located in the fourth ventricle and extending into the left cerebellopontine angle (CPA). A suboccipital craniotomy was performed and a gross-total resection of the mass was achieved. Pathological examination of the resected tissue confirmed the diagnosis of capillary hemangioma. To the authors' knowledge, this is the first reported case of a capillary hemangioma occurring in this location. The authors provide a review of the current literature on intracranial capillary hemangiomas and conclude that, despite the rarity of these lesions, they should be considered in the differential diagnosis of lesions in the fourth ventricle and/or the CPA in children.

Craniotomy↗
PubMed2005

Intracranial Ewing sarcoma.

The occurrence of primary extraosseous Ewing sarcoma (EES) of the central nervous system (CNS) has only rarely been reported in the literature. It is important to distinguish this entity from the more common central primitive neuroectodermal tumor (PNET) of brain, since the management of these tumors is different from that of EES. We present the clinical, radiologic, and pathologic features of two cases of EES occurring in the brain. The diagnosis was further confirmed by detection of a rearrangement of the FLI1 and/or EWS gene loci in tumors from both patients using fluorescent in situ hybridization (FISH). Although rare, the possibility of EES should be considered particularly when tumors that arise near the meningeal surface of the brain and have the pathologic appearance of a PNET. Demonstration of t(11;22)(q24;q12) by molecular analysis essentially confirms the diagnosis and enables the oncologist to choose appropriate therapy.

Brain Neoplasms↗
PubMed2005

Myxopapillary ependymoma and fatty filum in an adult with tethered cord syndrome: a shared embryological lesion? Case report.

OBJECTIVE AND IMPORTANCE: Myxopapillary ependymoma and fatty fila are traditionally thought to arise via completely different pathophysiologies. Recognition of these distinct pathologies in the same patient is important for appropriate treatment and prognosis. CLINICAL PRESENTATION: A 28-year-old woman presented with low back pain, bilateral leg radiculopathies, and mild leg weakness suggestive of tethered cord syndrome. Magnetic resonance imaging revealed lesions in the area of the conus medullaris consistent with a myxopapillary ependymoma and fatty filum. INTERVENTION: Under the surveillance of intraoperative electromyographic monitoring, the patient underwent an L4-S2 laminectomy for transection of the fatty filum and gross total resection of the mass. Histopathological examination confirmed the presence of these two distinct pathologies. CONCLUSION: We report an unusual case of a myxopapillary ependymoma coexisting with a fatty filum in an adult patient. To the best of our knowledge, this association has not yet been reported. This raises the interesting question of a possible associative or causative relationship between these distinct pathologies, which have traditionally been thought to arise from different mechanisms.

Cauda Equina↗
PubMed2005

Primary intraocular T-cell-rich large B-cell lymphoma.

We report a primary intraocular T-cell-rich large B-cell lymphoma in a 57-year-old woman who underwent 3 diagnostic vitrectomies for a presumed diagnosis of panuveitis. She developed no light perception in the left eye and underwent enucleation. Histopathologic and immunohistochemical studies on the enucleated globe disclosed a primary intraocular large B-cell lymphoma involving the choroid, vitreous, and retina. A large population of T cells was identified among the neoplastic B-cell population. B-cell immunoglobulin gene rearrangement and T-cell receptor gene rearrangement studies using the polymerase chain reaction method indicated that a monoclonal immunoglobulin kappa light chain population was present and that the T-cell population was not monoclonal. This case highlights the importance of interpreting cytologic features in vitreous aspirates in the context of the clinical situation.

Biomarkers, Tumor↗
PubMed2005

Collagen-rich crystalloids in a scarred vascularized cornea.

Collagen-rich crystalloids, also referred to as collagenous crystalloids, are uncommon findings in benign salivary gland tumors with myoepithelial differentiation and in cutaneous neoplasms. Herein, we report the presence of collagen-rich crystalloids in the scarred, vascularized cornea of a 56-year-old woman. The patient underwent penetrating keratoplasty, and microscopic examination of hematoxylin-eosin-stained sections disclosed large aggregates of refractile material within the corneal stroma. The deposits were partially birefringent when viewed with polarized light and composed of radially arranged columns (long rectangles) with rounded to pointed tips. The deposits had tinctorial properties of collagen using Masson trichrome and the van Gieson method for collagen, and they stained with Alcian blue, pH 2.5, and Verhoeff elastic stain. They did not stain with Gomori methenamine silver, Snook reticulin stain, or tyrosine using the Baker modification of the Millon reaction. This is the first report, to our knowledge, of collagen-rich crystalloids in the cornea. Their presence in the cornea indicates that these structures may occur in the absence of neoplasia.

Birefringence↗
PubMed2005

Clear cell hidradenoma: a mimic of metastatic clear cell tumors.

Clear cell hidradenoma is a benign skin appendage tumor that may mimic conventional-type renal cell carcinoma. Histologically, clear cell hidradenoma contains small ductular lumens, focal apocrine and squamoid change, and a less prominent vascular pattern than renal cell carcinoma. Furthermore, immunohistochemical studies can aid in distinguishing the 2 tumors. Knowing the cytologic features of primary skin adnexal neoplasms helps distinguish them from cutaneous metastases, which are more commonly referred for fine-needle aspiration biopsy evaluation. Detailed clinical history, physical findings, and ancillary studies are essential for correct diagnosis and categorization of these tumors. We report the rare case of a patient with renal cell carcinoma who underwent excision of an axillary clear cell hidradenoma, which was clinically suggestive of cutaneous metastatic disease.

Adenoma, Sweat Gland↗
PubMed2004

Radial optic neurotomy in the porcine eye without retinal vein occlusion.

OBJECTIVE: To demonstrate the histopathologic changes in the porcine eye without retinal vein occlusion after radial optic neurotomy (RON). METHODS: A RON was performed in 14 normal eyes of 12 Yorkshire Cross pigs. One radial stab incision at the edge of the nasal optic nerve head was made using a 20-gauge microvitreoretinal blade (Visitec) while the intraocular pressure was elevated. Surgery was concluded when hemostasis was achieved. Weekly ophthalmoscopic examinations were performed. Group 1 eyes (4 eyes of 2 pigs) were enucleated at the end of surgery. Group 2 eyes (4 eyes of 4 pigs) were enucleated 1 week postoperatively, and group 3 eyes (4 eyes of 4 pigs) were enucleated 3 weeks postoperatively. In group 4 (2 eyes of 2 pigs), animals underwent vitrectomy and RON, and eyes were enucleated 3 weeks postoperatively. RESULTS: Ophthalmoscopic examination demonstrated engorged blood vessels at the RON site up to 3 weeks after surgery with minimal or no hemorrhage. Histological examination of the optic nerve demonstrated foci of hemorrhage, interstitial edema, reactive gliosis, and rare inflammatory cells. At 3 weeks, there was complete axonal nerve fiber loss distal to the neurotomy site. CONCLUSIONS: After RON, marked gliosis and complete axonal nerve fiber loss occur at the neurotomy site. Although bleeding was rare intraoperatively in this porcine model, hemorrhage and interstitial edema were present within the optic nerve at the neurotomy site histologically. Clinical Relevance Radial optic neurotomy remains a controversial method of treatment for central retinal vein occlusion. To our knowledge, this is the first study in the literature describing the histopathologic findings after RON.

Animals↗
PubMed2004

A lethal association of congenital apnea with brainstem tegmental necrosis.

We present a female with premature birth, polyhydramnios, congenital apnea, cranial nerve palsies, orofacial and limb anomalies. Neuroimaging revealed calcifications along the vental margin of the caudal fourth ventricle. Neuropathologic findings at postmortem examination were consistent with brainstem tegmental necrosis and olivary hypoplasia, a rare lethal entity that should be considered in the differential diagnosis of congenital apnea.

Abnormalities, Multiple↗
PubMed2004

Effects of indocyanine green on the retina and retinal pigment epithelium in a porcine model of retinal hole.

PURPOSE: This study was designed to emulate human macular hole surgery and to test the effects of indocyanine green (ICG) on the retina and retinal pigment epithelium (RPE). METHODS: Yorkshire Cross pigs (n = 23) underwent vitrectomy, separation of the posterior cortical vitreous, and creation of a single retinal hole. In three study groups (n = 6, each group), air-fluid exchange was performed, following which balanced salt solution (BSS), 1.0% ICG, or 0.5% ICG was applied over the retinal hole. In one additional group (n = 5), 0.5% ICG was injected into the fluid-filled eye. At 4 weeks, the eyes were examined clinically, and fundus photographs were obtained before enucleation and light microscopic examination. RESULTS: Clinical evaluations documented a statistically significant difference between study groups (P = 0.036). There was a higher rate of moderate or severe RPE atrophy among animals where 1% or 0.5% ICG was applied in air-filled eyes (83% and 67%, respectively) compared with BSS controls (17%) and fluid-filled eyes receiving 0.5% ICG (40%). Histologic evaluation demonstrated a statistically significant difference between groups (P = 0.044), with extensive outer retinal degeneration observed in air-filled eyes receiving 1% or 0.5% ICG (66% and 60%, respectively) compared with BSS controls or fluid-filled eyes receiving 0.5% ICG (none of the eyes in either group). None of the study groups had any changes in the inner retina except at the retinal hole site. CONCLUSIONS: Retina exposed to ICG concentrations used in human vitreoretinal surgery had greater RPE atrophy and outer retinal degeneration than control eyes undergoing the same surgery without ICG. Eyes filled with infusion fluid during ICG injection had less damage to the RPE and outer retina than did air-filled eyes receiving ICG.

Air↗
PubMed2004

Xanthogranuloma of the sciatic nerve: case report.

OBJECTIVE AND IMPORTANCE: Xanthogranulomas involving the central or peripheral nervous system are extraordinarily rare. None have been reported in the lower extremity. Here, we report and characterize the first case of xanthogranuloma of the sciatic nerve. CLINICAL PRESENTATION: A 58-year-old woman presented with poorly localized right back and groin pain. Magnetic resonance imaging studies revealed an enhancing lesion of the sciatic nerve in the right gluteal region. INTERVENTION: The sciatic nerve xanthogranuloma was resected without complication. CONCLUSION: Our report indicates that xanthogranuloma, although extremely rare, may occur throughout the nervous system. Our evaluation demonstrates that such lesions involving the peripheral nervous system have similar pathological characteristics to xanthogranulomas that more commonly occur in the skin.

Female↗
PubMed2003

Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model.

We employed a genetically defined human cancer model to investigate the contributions of two genes up-regulated in several cancers to phenotypic changes associated with late stages of tumorigenesis. Specifically, tumor cells expressing two structurally unrelated bone-related genes, osteonectin and osteoactivin, acquired a highly invasive phenotype when implanted intracranially in immunocompromised mice. Mimicking a subset of gliomas, tumor cells invaded brain along blood vessels and developed altered vasculature at the brain-tumor interface, suggesting that production of those two proteins by tumor cells may create a complex relationship between invading tumor and vasculature co-opted during tumor invasion. Interestingly, the same tumor cells formed massive spontaneous metastases when implanted subcutaneously. This dramatic alteration in tumor phenotype indicates that cellular microenvironment plays an important role in defining the specific effects of those gene products in tumor behavior. In vitro examination of tumor cells expressing either osteonectin or osteoactivin revealed that there was no impact on cellular growth or death but increased invasiveness and expression of MMP-9 and MMP-3. Specific pharmacologic inhibitors of MMP-2/9 and MMP-3 blocked the increased in vitro invasion associated with osteoactivin expression, but only MMP-3 inhibition altered the invasive in vitro phenotype mediated by osteonectin. Results from this genetically defined model system are supported by similar findings obtained from several established tumor cell lines derived originally from human patients. In sum, these results reveal that the expression of a single bone-related gene can dramatically alter or modify tumor cell behavior and may confer differential growth characteristics in different microenvironments. Genetically defined human cancer models offer useful tools in functional genomics to define the roles of specific genes in late stages of carcinogenesis.

Animals↗
PubMed2003

The immunohistochemical profile of the tethered filum terminale.

The embryopathy underlying tethering of the filum terminale is poorly understood. Knowledge of normal filum development is the foundation upon which to compare normal fila to fila from patients with tethered cord syndrome. Thirty-four fila from patients with tethered cord syndrome were immunostained with caudal neural tube developmental markers H4C4 (CD44), VIN-IS-53, AC4, FP3 and NOT1, and a panel of mature neuroglial, neural crest, epithelial and mesenchymal markers. H4C4 (CD44) and NOT1 exhibited significant alterations in immunoexpression in tethered fila compared to controls. The change in expression may be indicative of altered cell identity in the filum and constitute the predisposition to tethering.

Adolescent↗