Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours.
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Antigens, CD↗
Biomedical subjects
N Weidner
Publications and source records attributed to N Weidner.
Spontaneous plasticity in the injured spinal cord-implications for repair strategies.
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Afferent Pathways↗
Spontaneous corticospinal axonal plasticity and functional recovery after adult central nervous system injury.
Although it is believed that little recovery occurs after adult mammalian spinal cord injury, in fact significant spontaneous functional improvement commonly occurs after spinal cord injury in humans. To investigate potential mechanisms underlying spontaneous recovery, lesions of defined components of the corticospinal motor pathway were made in adult rats in the rostral cervical spinal cord or caudal medulla. Following complete lesions of the dorsal corticospinal motor pathway, which contains more than 95% of all corticospinal axons, spontaneous sprouting from the ventral corticospinal tract occurred onto medial motoneuron pools in the cervical spinal cord; this sprouting was paralleled by functional recovery. Combined lesions of both dorsal and ventral corticospinal tract components eliminated sprouting and functional recovery. In addition, functional recovery was also abolished if dorsal corticospinal tract lesions were followed 5 weeks later by ventral corticospinal tract lesions. We found extensive spontaneous structural plasticity as a mechanism correlating with functional recovery in motor systems in the adult central nervous system. Experimental enhancement of spontaneous plasticity may be useful to promote further recovery after adult central nervous system injury.
Animals↗
p53 immunoreactivity correlates with Ki-67 and bcl-2 expression in renal cell carcinoma.
This study assessed the relation of proliferation, inhibition of apoptosis, and the p53 tumor suppressor protein expression in clear renal cell carcinoma (RCC). Archival pathological specimens from 43 patients treated for RCC were obtained. Median follow-up for the patients was 52 months (range 2.5 months to 178 months). Immunostaining of paraffin tissue sections was carried out for four different markers: a) Ki-67, a marker for cellular proliferation; b) p53/DO7, c) p53/pAb240, antibodies for the p53 protein; and d) bcl-2, a marker for inhibition of apoptosis (programmed cell death). One thousand cells were counted per slide at 400x magnification. Staining of >/=10% of cells was considered positive and <10% negative. Fisher exact contingency tables were used for correlation between markers, tumor grade and stage. A significant correlation was found between Ki-67 and p53 immunoreactivity samples, P=0.0001. Interestingly, a significant association was found if Ki-67 and bcl-2 scores were combined and correlated with p53, P=0.009. Results showed no correlation between any of the immunohistochemical markers and grade or stage. In addition, Kaplan-Meier survival curves demonstrated no significant difference between patients' tumors that was scored immunoreactive negative vs. positive for Ki-67, p53, or bcl-2. This study indicates that p53 expression correlates with proliferation, and inhibition of programmed cell death in RCC.
Journal Article↗
Primary hepatic anaplastic large-cell lymphoma of T-cell phenotype in acquired immunodeficiency syndrome: a report of an autopsy case and review of the literature.
Anaplastic large-cell lymphomas (ALCL) were first described by Stein et al. in 1985 as large-cell neoplasms with a pleomorphic appearance, subtotal effacement of the lymph node structure, and expression of the lymphoid activation antigen CD-30 (Ki-l). Since their first description, these tumors have been documented in a variety of extranodal sites. We report a primary hepatic anaplastic large-cell lymphoma in a patient with advanced AIDS, who presented with hepatic failure and multiple nodules in the liver. A complete autopsy showed discrete tumor nodules throughout the entire liver without gross or microscopic involvement of lymph nodes or any other organs by the neoplastic process. The tumor cells showed typical histological and immunohistochemical features of ALCL and were strongly immunoreactive with the T-cell markers CD-3 and UCHL-1. Only one previous case of primary hepatic ALCL has been reported in the literature, and this tumor occurred in an immunocompetent patient and was not immunoreactive for B- or T-cell markers. To our knowledge, this study represents the first reported case of primary hepatic anaplastic large-cell lymphoma of T-cell phenotype. Additionally, this is the first case of primary hepatic ALCL reported in an AIDS patient.
Adult↗
Introduction. Vasculitis.
The vasculitides commonly create diagnostic and management problems, and a biopsy diagnosis of vasculitis usually does not stand alone in the proper medical management of a patient. Indeed, a conclusive diagnosis usually cannot be made without correlation with the patient's clinical history, physical findings, and/or angiographic findings. Nonetheless, a definitive diagnosis depends on histologic examination because few vasculitic syndromes have specific clinical and laboratory findings. Moreover, the histopathologic diagnosis depends on pathologist experience, tissue selection, sample size, chronologic age of the biopsied lesion(s), and effects of prior treatment. In this issue of Seminars in Diagnostic Pathology the important systemic vasculities are reviewed and updated. These include: polyarteritis nodosa, microscopic polyangiitis (microscopic polyarteritis), cutaneous leukocytoclastic vasculitis, Wegener's granulomatosis, giant-cell vasculitides, localized vasculitis, and angiocentric lymphomas (lymphomatous vasculitis).
Consensus Statements as Topic↗
Giant-cell vasculitides.
Although many of the vasculitides within the classification of the American College of Rheumatology can have a component of granulomatous inflammation with giant cells, two (ie, giant-cell [temporal] arteritis and Takayasu arteritis) are characterized by infiltrates that are dominated by granulomatous and/or giant-cell-containing inflammation. Furthermore, granulomatous and/or giant-cell dominant infiltrates can characterize disseminated giant-cell arteritis, granulomatous vasculitis of the central nervous system, localized giant-cell arteritis, mesenteric inflammatory veno-occlusive disease, primary cutaneous phlebitis, and giant-cell phlebitis of mesenteric veins and/or omentum. Like the other systemic vasculitides, there is considerable clinicopathologic overlap between these giant-cell vasculitides. Indeed, they are likely closely related, but how they specifically relate to each other is not clear. Their accurate diagnosis is important; because serious morbidity and even death may occur, if proper treatment is delayed or if excessive immunotherapy is given.
Aged↗
Primary anaplastic large cell lymphoma of the adrenal gland.
Primary adrenal lymphomas are rare. Most reported cases are of B-cell phenotype and follow an aggressive clinical course. We report a case of primary anaplastic large cell, CD30+ adrenal lymphoma developing in a 62-year-old woman. The patient presented with fatigue and vague right upper quadrant pressure. Computed tomography revealed bilateral adrenal masses. A right adrenalectomy was performed. Histologic evaluation showed islands of large atypical cells surrounded by eosinophilic acellular material. The tumor cells stained positive for CD45, CD45RO, CD43, and CD30. Epstein-Barr virus genome was identified in tumor cells using in situ hybridization. The patient was treated with chemotherapy and a 23-month follow-up examination showed no change in the size of the opposite adrenal gland and no other evidence of lymphoma.
Adrenal Gland Neoplasms↗
Endothelial-like cells derived from human CD14 positive monocytes.
In the present study, we show that endothelial-like cells (ELCs) can develop from human CD14-positive mononuclear cells (CD14 cells) in the presence of angiogenic growth factors. The CD14 cells became loosely adherent within 24 h of culture and subsequently underwent a distinct process of morphological transformation to caudated or oval cells with eccentric nuclei. After 1 week in culture the cells showed a clear expression of endothelial cell markers, including von Willebrand factor (vWF), CD144 (VE-cadherin), CD105 (endoglin), acetylated low-density lipoprotein (AC-LDL)-receptor, CD36 (thrombospondin receptor), FLT-1, which is vascular endothelial cell growth factor (VEGF) receptor-1, and, to a weaker extent, KDR (VEGF receptor-2). Furthermore, in these cells structures resembling Weibel-Palade bodies at different storage stages were identified by electron microscopy, and upon culturing on three-dimensional fibrin gels the cells build network-like structures. In addition, cell proliferation and vWF expression was stimulated by VEGF, and the endothelial cell adhesion molecules CD54 (ICAM-1), and CD106 (VCAM-1) became transiently inducible by tumor necrosis factor-alpha (TNF-alpha). In contrast, the dendritic markers CD1a, and CD83 were not expressed to any significant extent. The expression of CD68, CD80 (B7-1), CD86 (B7-2), HLA-DR and CD36 may also suggest that ELCs might be related to macrophages, sinus lining or microvascular endothelial cells. Taken together, our observations indicate that ELCs can differentiate from cells of the monocytic lineage, suggesting a closer relationship between the monocyte/macrophage- and the endothelial cell systems than previously supposed.
Antigens, Differentiation↗
Continuous epidural butorphanol relieves pruritus associated with epidural morphine infusions in children.
We examined the efficacy of epidural butorphanol to either prevent or relieve pruritus associated with epidural morphine infusion in children. Forty-six children were randomized to receive either epidural morphine (M) or epidural M with butorphanol (B) for postoperative analgesia. They received bupivacaine and either M 50 microg.kg-1 or the same dose of M plus B 10 microg.kg-1. Following surgery, a continuous infusion of 0.1% bupivacaine with either M 20 microg.ml-1 or M 20 microg.ml-1 + B 4 microg.ml-1 was given at a rate of 0.3 ml.kg-1.h-1. Pain scores and pruritus scores were recorded every 4 h during epidural infusion. Subjects with a pruritus score=2 received diphenhydramine 0.5 mg.kg-1 i.v. and were switched to an alternate epidural infusion; subjects receiving M (group M) were switched to M+B while subjects receiving M+B (group B) were switched to hydromorphone (H) 4 microg.ml-1. There was no difference in the initial incidence of pruritus (group M 11/18; group B 13/28). No subject in group M required a second change of epidural infusion because of continued pruritus after being switched to M+B; five of 13 subjects in group B continued to experience pruritus after being switched to H and required a second change of epidural infusion or an alternate analgesic modality (P=0.038). The median pruritus score in the first 24 h after changing epidural infusions was 0 in subjects in group MDelta (changed from M to M+B) and 1 in subjects in group BDelta (changed from M+B to H; P=0.012). While the median sedation score in the first 24 h was 1 in both groups, there was a greater incidence of sedation scores of 2 in group B than group M (28% vs 12.3%; P=0.021). B 10 microg.kg-1 was not effective in preventing pruritus associated with bolus epidural administration of M 50 microg.kg-1 in children. B 1.2 microg.kg-1. h-1 was effective in relieving pruritus associated with continuous epidural infusion of M 6 microg.kg-1.h-1.
Adolescent↗
Angiogenesis as a predictor of clinical outcome in cancer patients.
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Female↗
Papillary and follicular neoplasms of the thyroid gland. Differential immunohistochemical staining with high-molecular-weight keratin and involucrin.
The morphologic distinction between papillary and follicular neoplasms of the thyroid gland can be difficult, especially on small biopsy specimens or in fine-needle aspirations. To determine whether immunohistochemistry could help in achieving the correct diagnosis, we characterized the staining pattern for a series of papillary and follicular neoplasms of the thyroid gland. A pilot study was performed using a panel of antibodies, including high-molecular-weight keratin (HMWK, 34 beta E12), cytokeratin (CK) 5/6, CK7, CK13, CK14, CK20, AE1/AE3, CAM5.2, involucrin, and villin. Of these antibodies, involucrin and HMWK showed strong differential staining between follicular and papillary neoplasms. HMWK stained 91% of papillary carcinomas, including follicular variants, with a median of 53% positive cells, and involucrin stained 72.5% of papillary neoplasms with a median of 45% positive cells. HMWK stained only 20% of follicular neoplasms, whereas involucrin stained 29% of cases. Papillary neoplasms showed strong, although patchy, staining with HMWK and involucrin, whereas those follicular neoplasms that did have staining showed a weak, diffuse pattern of staining. We believe that HMWK, and involucrin to a lesser degree, could be useful in differentiating papillary from follicular neoplasms, especially for cytologic cell block material or for cases in which the architectural pattern is follicular.
Adenocarcinoma, Follicular↗
Immunohistochemistry of small round-cell tumors.
The term "small round-cell tumor" describes a group of highly aggressive malignant tumors composed of relatively small and monotonous undifferentiated cells with high nuclear to cytoplasmic ratios. This group includes Ewing's sarcoma (ES), peripheral neuroepithelioma (aka, primitive neuroectodermal tumor or extraskeletal ES), peripheral neuroblastoma ("classic-type"), rhabdomyosarcoma, desmoplastic small round-cell tumor, lymphoma, leukemia, small-cell osteosarcoma, small-cell carcinoma (either undifferentiated or neuroendocrine), olfactory neuroblastoma, cutaneous neuroendocrine carcinoma (aka, Merkel-cell carcinoma), small-cell melanoma, and mesenchymal chondrosarcoma. Their clinical presentations often overlap, thus making a definitive diagnosis problematic in some cases. Yet, a clear understanding of their clinicopathologic features usually allows for a confident diagnosis, especially if immunohistochemistry is used. The following is a review of the immunohistochemistry of this small round-cell tumor group.
Biomarkers, Tumor↗
Nerve growth factor-hypersecreting Schwann cell grafts augment and guide spinal cord axonal growth and remyelinate central nervous system axons in a phenotypically appropriate manner that correlates with expression of L1.
Schwann cells contribute to efficient axonal regeneration after peripheral nerve injury and, when grafted to the central nervous system (CNS), also support a modest degree of central axonal regeneration. This study examined (1) whether Schwann cells grafted to the CNS exhibit normal patterns of differentiation and association with spinal axons and what signals putatively modulate these interactions, and (2) whether Schwann cells overexpressing neurotrophic factors enhance axonal regeneration. Thus, primary Schwann cells were transduced to hypersecrete human nerve growth factor (NGF) and were grafted to spinal cord injury sites in adult rats. Comparisons were made to nontransfected Schwann cells. From 3 days to 6 months later, grafted Schwann cells exhibited a phenotypic and temporal course of differentiation that matched patterns normally observed after peripheral nerve injury. Schwann cells spontaneously aligned into regular spatial arrays within the cord, appropriately remyelinated coerulospinal axons that regenerated into grafts, and appropriately ensheathed but did not myelinate sensory axons extending into grafts. Coordinate expression of the cell adhesion molecule L1 on Schwann cells and axons correlated with establishment of appropriate patterns of axon-Schwann cell ensheathment. Transduction of Schwann cells to overexpress NGF robustly increased axonal growth but did not otherwise alter the nature of interactions with growing axons. These findings suggest that signals expressed on Schwann cells that modulate peripheral axonal regeneration and myelination are also recognized in the CNS and that the modification of Schwann cells to overexpress growth factors significantly augments their capacity to support extensive axonal growth in models of CNS injury.
Animals↗
Tumour vascularity and proliferation: clear evidence of a close relationship.
Evaluation of various prognostic factors often reveals that some are closely related. In this issue of the Journal of Pathology, evidence is presented linking intratumoural microvessel density with tumour cell proliferation. This is expected, because an adequate blood vascular system is necessary for effective tumour cell proliferation. The blood vascular supply of a tumour is critical not only in providing tumour cells with nutrients, oxygen, and waste elimination, but also because activated endothelial cells release important paracrine growth factors for tumour cells and secrete collagenases, urokinases, and plasminogen activator. The latter allow capillary ingrowth and the spread of tumour cells into and through the adjacent fibrin-gel matrix, connective tissue stroma, and into the lymphatic and/or vascular spaces. Finally, an adequate vascular supply helps to 'switch off' apoptosis and prevent other forms of tumour necrosis, thus contributing to overall tumour growth and spread.
Cell Division↗
Elimination of basal lamina and the collagen "scar" after spinal cord injury fails to augment corticospinal tract regeneration.
The production of specific extracellular matrix molecules is upregulated following injury to the adult CNS, and some of these molecules have been postulated to inhibit axonal regeneration. In particular, the deposition of collagen in conjunction with basal lamina formation has been correlated with the failure of CNS axons to extend beyond sites of injury. In the present experiment, the spatial and temporal distribution of fibrillar collagen type III and the main constituents of basal lamina (collagen type IV and laminin) were characterized after defined lesions of the adult spinal cord at cervical and thoracic levels. The deposition of collagen was then blocked in animals undergoing defined mid-thoracic spinal cord lesions by administration of the iron chelator 2,2'-bipyridine, and subsequent effects on corticospinal axonal growth were examined. At time points from 1 to 6 weeks postinjury, collagen and laminin were deposited at spinal cord lesion sites as a dense matrix at the host-lesion interface that extended for short distances into the surrounding spinal cord parenchyma. The failure of corticospinal axons to grow beyond the lesioned region correlated spatially and temporally with collagen III formation and basal lamina production. However, successful blockade of collagen and basal lamina formation with 2,2'-bipyridine injections failed to enhance corticospinal axon regeneration or sprouting. These results suggest either that collagen and basal lamina formation after CNS injury do not contribute to corticospinal axonal growth failure or, more likely, that molecules in addition to collagen and basal lamina contribute to axonal growth failure and must be collectively blocked to promote corticospinal regeneration.
2,2'-Dipyridyl↗
Germ-cell tumors of the mediastinum.
Mediastinal germ-cell tumors (GCTs) usually occur within the anterior mediastinum, accounting for about 15% of all mediastinal cysts and tumors. They are associated with the thymus, presumably arising from extragonadal germ cells or thymic cells with germ-cell potential. Mediastinal seminoma develops primarily in young males with rare cases reported in females; likewise, embryonal carcinoma, endodermal sinus tumor or yolk-sac tumor, choriocarcinoma, and malignant mixed or combined GCTs also overwhelmingly affect males. Mature cystic teratoma affects males and females equally. The prognosis for mediastinal mature cystic teratoma and seminoma is very good. Nonseminomatous malignant GCTs of the mediastinum often present with advanced disease and do not respond as well to chemotherapy as their gonadal counterparts. Nonetheless, it is important to separate mediastinal GCTs from other undifferentiated malignant tumors, especially thymic carcinoma, which has a poor prognosis. Clearly, some patients with mediastinal GCTs respond very well to modern therapies.
Adolescent↗
Tumoural vascularity as a prognostic factor in cancer patients: the evidence continues to grow.
Accurate prognostic indicators would help in identifying patients at high risk for recurrence and death. Recent and previous studies indicate that intratumoural microvessel density (iMVD) of invasive breast carcinoma (a measure of tumour angiogenesis) is associated with aggressive tumour growth; iMVD may thus be a valuable prognostic indicator. Moreover, the bulk of accumulating data indicates that microvessel density in the area of most intense neovascularization in invasive breast carcinoma is an independent, significant and accurate prognostic indicator in predicting poorer survival. Such an indicator would be useful in the selection of high-risk patients with breast carcinoma for systemic adjuvant therapy.
Breast Neoplasms↗