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PubMed1993

Clusters of chromosome 9 aberrations are associated with clinico-pathologic subsets of non-Hodgkin's lymphoma.

In this study we analyzed nonrandom aberrations affecting chromosome 9 in a series of 426 consecutively ascertained, karyotypically abnormal non-Hodgkin's lymphoma (NHL) tumors derived from 407 patients. Cytogenetic abnormalities were correlated with clinical, histologic, and immunologic features. Structural abnormalities of chromosome 9 were identified in 60 specimens derived from 59 patients. The recurring abnormalities among these were associated with 4 clinico-pathologic subsets. The first comprised 7 cases of t(9;14)(p13;q32), 6 of which had small lymphocytic lymphoma, plasmacytoid subtype, and an indolent clinical course. The second group included 12 cases with breaks at 9q11-13 and diffuse lymphomas with a large-cell component and a typical response to combination chemotherapy. The third group was comprised of 7 cases with 9q deletions, with a common deleted region encompassing 9q31-32. These cases were characterized by diffuse B-cell histology, young age, and poor clinical outcome. The fourth subset included 5 intermediate- to high-grade T-cell tumors with breaks at 9q34. This analysis of chromosome 9 aberrations in NHL comprises the first such effort based on a large series of tumors. We identify and report here new clinico-pathologic subsets with shared abnormalities of chromosome 9, which should facilitate new approaches to the analysis of the etiology and clinical behavior of NHL.

Biopsy↗

PubMed1999

Adenomas and adenoma-like DALMs in chronic ulcerative colitis: a clinical, pathological, and molecular review.

Dysplasia in chronic ulcerative colitis (CUC) is categorized as either flat or associated with a raised lesion or mass (dysplasia-associated lesion or mass [DALM]). One specific subtype of DALM consists of an isolated discrete "adenoma-like" polypoid dysplastic lesion that is difficult to distinguish from a sporadic adenoma that occurs coincidentally in patients with CUC. Sporadic adenomas are, by definition, also polypoid dysplastic lesions, but their development is unrelated to the underlying colitis. The clinical distinction between CUC-associated polypoid dysplastic lesions and sporadic adenomas is important because the former is an indication for colectomy whereas the latter is usually treated by simple polypectomy. This review focuses on the clinical, pathological, and molecular aspects of polypoid dysplastic lesions and sporadic adenomas in CUC. There are a variety of clinical and pathological features that can be used to distinguish these lesions, but none of these features are entirely specific for either type of neoplasm. Furthermore, there is recent evidence to suggest that the molecular pathogenesis of CUC-associated polypoid dysplasia is different, in terms of the order and timing of genetic events, in comparison to sporadic adenomas and, thus, this information may be used to distinguish these lesions in the near future. Few studies have evaluated the natural history of CUC-related polypoid dysplastic lesions and sporadic adenomas. However, recent reports indicate that the majority of these lesions will follow a relatively benign course with a low risk of progression to flat dysplasia or adenocarcinoma. This review also summarizes the current provisional treatment recommendations for CUC patients with an adenoma-like polypoid dysplastic lesion.

Adenomatous Polyps↗

PubMed2002

Calcium channel subtypes contributing to acetylcholine release from normal, 4-aminopyridine-treated and myasthenic syndrome auto-antibodies-affected neuromuscular junctions.

1 Acetylcholine release at the neuromuscular junction relies on rapid, local and transient calcium increase at presynaptic active zones, triggered by the ion influx through voltage-dependent calcium channels (VDCCs) clustered on the presynaptic membrane. Pharmacological investigation of the role of different VDCC subtypes (L-, N-, P/Q- and R-type) in spontaneous and evoked acetylcholine (ACh) release was carried out in adult mouse neuromuscular junctions (NMJs) under normal and pathological conditions. 2 omega-Agatoxin IVA (500 nM), a specific P/Q-type VDCC blocker, abolished end plate potentials (EPPs) in normal NMJs. However, when neurotransmitter release was potentiated by the presence of the K(+) channel blocker 4-aminopyridine (4-AP), an omega-agatoxin IVA- and omega-conotoxin MVIIC-resistant component was detected. This resistant component was only partially sensitive to 1 micro M omega-conotoxin GVIA (N-type VDCC blocker), but insensitive to any other known VDCC blockers. Spontaneous release was dependent only on P/Q-type VDCC in normal NMJs. However, in the presence of 4-AP, it relied on L-type VDCCs too. 3 ACh release from normal NMJs was compared with that of NMJs of mice passively injected with IgGs obtained from patients with Lambert-Eaton myasthenic syndrome (LEMS), a disorder characterized by a compromised neurotransmitter release. Differently from normal NMJs, in LEMS IgGs-treated NMJs an omega-agatoxin IVA-resistant EPP component was detected, which was only partially blocked by calciseptine (1 micro M), a specific L-type VDCC blocker. 4 Altogether, these data demonstrate that multiple VDCC subtypes are present at the mouse NMJ and that a resistant component can be identified under 'pharmacological' and/or 'pathological' conditions.

4-Aminopyridine↗

PubMed2000

Malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms.

BACKGROUND: The purpose of the current study was to determine the distribution and relative frequency of each subtype of malignant lymphoma in southern Taiwan according to the revised European-American classification of lymphoid neoplasms (REAL). METHODS: The pathology files of a regional hospital in southern Taiwan for 1989-1998 were searched for malignant lymphoma, lymphoproliferative disorder, and Hodgkin disease (HD). The results of light microscopy, immunohistochemistry, and in situ hybridization for Epstein-Barr virus-encoded RNA (EBER) were correlated with clinical findings, and all cases were classified according to REAL. RESULTS: A total of 205 cases were analyzed retrospectively. There were 197 cases (96.1%) of non-Hodgkin lymphoma (NHL) and 8 cases (3. 9%) of HD. Among the 197 NHL cases, 161 (81.7%) were of B-cell lineage and 36 (18.3%) were of T-/natural killer cell lineage. Diffuse large B-cell lymphoma, extranodal marginal zone lymphoma, and follicular lymphoma were the most common B-cell subtypes and represented 47.2%, 19.3%, and 6.1%, respectively, of all NHL cases. Among the 36 cases of T-/natural killer cell lineage, unspecified peripheral T-cell lymphoma (8.6%), T-/natural killer cell lymphoma (angiocentric lymphoma) (4.1%), and anaplastic large cell lymphoma (3.6%) were the most common subtypes. Seven of eight T-/natural killer cell lymphoma cases were positive for EBER. The eight cases of HD were classified as lymphocyte-rich classic (two cases), nodular sclerosis (two cases), and mixed cellularity (four cases) subtypes. Three of these eight cases were positive for EBER. CONCLUSIONS: To the authors' knowledge this study is the first in Taiwan using the REAL classification and it again confirms the different geographic distribution of the various subtypes of malignant lymphoma. The frequency of T-/natural killer cell lineage NHL in Taiwan is higher than that in Western countries but not as high as reported previously.

Geography↗

PubMed1989

Expression of GCDFP-15 in breast carcinomas. Relationship to pathologic and clinical factors.

A retrospective immunoperoxidase staining study for a glycoprotein isolated from human breast gross cystic disease fluid (GCDFP-15) in 562 primary breast carcinomas in 539 patients was conducted to correlate its immunohistochemistry with pathologic and clinical factors. Overall, 55% of the carcinomas studied stained positively for GCDFP-15. In certain histologic subtypes, the percentage of carcinomas that stained positively was greater: those subtypes with apocrine histologic features (75%), intraductal carcinoma (70%), and infiltrating lobular carcinoma with signet-ring cell differentiation (90%). In contrast, only 5% of medullary carcinomas exhibited positive staining. Only 23% of breast carcinomas without apocrine features stained positively for GCDFP-15. Carcinomas that stained positively were more likely to have involved axillary lymph nodes (P less than 0.054). The staining was independent of nuclear grade, mitotic index, tumor size, and estrogen receptor status. Positive staining was related to a history of gross cystic disease but not to age, parity, menopausal status, or age at first birth. A positive stain was not related to risk of recurrence or survival.

Apolipoproteins↗

PubMed1986

Hodgkin's disease in homosexual men. An AIDS-related phenomenon?

Five cases of Hodgkin's disease in young homosexual men at risk for the acquired immune deficiency syndrome (AIDS) are reported. The mixed cellularity histologic subtype was present in each. Two also showed features of lymphocyte depletion. Four of the five patients had pathologic stage IIIB or IVB disease at presentation. In the fifth, recurrent Hodgkin's disease developed in a previously irradiated field. Three patients had opportunistic infections characteristic of AIDS. Hodgkin's disease may pursue a more fulminant course in patients at risk for AIDS and may itself be a manifestation of AIDS in this high-risk population.

Acquired Immunodeficiency Syndrome↗

PubMed1995

Central and peripheral dopamine D1/DA1 receptor modulation of gastric secretion and experimental gastric mucosal injury.

1. Dopamine D1 (central)/DA1 (peripheral) receptors are believed to influence gastrointestinal function and pathology. 2. When given i.c.v. or i.p., an agonist (SKF38393) and an antagonist (SCH23390) of this DA receptor subtype inhibit and enhance, respectively, gastric secretion and gastric mucosal injury. 3. When given both i.c.v. and i.p., their respective effects in the gut were amplified. 4. Antagonist or agonist given i.p., blocked the corresponding protective and worsening effect of the agonist or antagonist given i.c.v. 5. Both central and peripheral D1/DA1 receptors modulate gastric function and response to injury.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2004

Somatostatin receptor distribution and function in immune system.

Somatostatin and cortistatin, a recently discovered endogenous neuropeptide relative of somatostatin, have multiple modulatory effects on the immune system. The specific somatostatin receptor distribution might in part explain the heterogeneity of effects of somatostatin or its analogs on immunocytes. In fact, somatostatin receptor subtypes are differentially expressed on specific cell subsets within the organs of the immune system and the expression is dynamically regulated and seems to depend on the traffic of these cells through and within lymphoid structure and homing in tissues. Somatostatin effects on immune cells are mainly based on autocrine and paracrine modes of action. In fact, activated cells producing somatostatin (or cortistatin) may interact with other cells expressing the receptors. Here, we review the postulated modes of action of somatostatin and somatostatin-like peptides, including the currently available synthetic somatostatin analogs, in cells of the immune system. We also discuss the wide distribution of somatostatin and its specific five receptor subtypes in immune cell lines, as well as throughout animal and human lymphoid organs, in both normal and pathological conditions.

Animals↗

PubMed2003

Lymphomas.

Hodgkin's and non-Hodgkin's lymphomas are an important part of the differential diagnosis of head and neck tumors. Their diagnosis begins with a complete history and physical examination and is confirmed with an appropriately obtained and prepared pathologic specimen. Prognosis and therapy of the lymphomas vary depending on stage and the characteristics of each particular subtype of lymphoma. Low-grade lymphomas and chronic lymphocytic leukemia are characterized by long survival times and are most often treated with palliative intent. More aggressive high-grade lymphomas are treated for cure. Although chemotherapy and radiotherapy remain the mainstays of treatment, immunotherapy demonstrates increasing promise.

Head and Neck Neoplasms↗

PubMed2006

Complete surgical resection of high-grade astroblastoma with long time survival: case report and review of the literature.

Astroblastoma is a rare glial neoplasm of unknown origin and uncertain prognosis. It usually presents in young adults as a well circumscribed hemispheric mass, often associated with a cystic component. The histological features of astroblastoma are the presence of typical astroblastic perivascular pseudorosettes and perivascular hyalinization. Two different subtypes of astroblastoma have been defined based upon histological characteristics. Prognosis, however, sometimes is in contradiction with the pathological appearance and seems to be more closely related to the grade of surgical resection. We present a new case of a patient with a high-grade astroblastoma with a long survival time, in whom complete surgical resection was confirmed by an early postoperative MRI.

Adult↗

PubMed2004

Differential prevalence of anti-heparin-PF4 immunoglobulin subtypes in patients treated with clivarin and heparin: implications in the HIT pathogenesis.

Heparin-induced thrombocytopenia (HIT) syndrome is a catastrophic complication of heparin therapy that may result in arterial/venous thromboembolic events. The pathophysiology of HIT is mediated by the generation of a functionally and molecularly heterogeneous group of anti-heparin-platelet factor 4 (AHPF4) antibodies that cause platelet/endothelial cell activation/destruction. These AHPF4 antibodies may be of various subtypes and cause differential pathogenic responses during HIT. This study evaluated the differential prevalence and functionality of AHPF4 Ig subtypes (IgA, IgG, and IgM) in plasma samples obtained from clinically suspected HIT patients (n = 111) and two clinical trials. In these trials, a low-molecular-weight heparin, clivarin and unfractionated heparin (UFH) were used to treat deep-vein thrombosis (CORTES) and for prophylaxis of the orthopedic surgery (ECHOS). In the CORTES study, three randomized groups of patients (n = 312-328) received prophylactic treatment with either UFH or clivarin (o.d. or b.i.d.). In the ECHOS study, there were approximately 600 patients per group. Citrated plasma samples were analyzed for cumulative IgA/IgG/IgM and individual Ig subtypes of AHPF4 utilizing ELISA. Functionality of the ELISA-positive samples was ascertained by 14C-serotonin release assay. In clinically confirmed HIT patients (and UFH-treated CORTES and ECHOS samples), the Ig subtyping revealed a predominance of IgG AHPF4 antibodies in contrast to the asymptomatic high AHPF4 antibody titers, which were found to be mostly IgM and/or IgA subtypes. In the clivarin-treated patients in both trials, the prevalence of AHPF4 antibodies was found to be lower (2-3 fold, p < 0.01) in comparison to UFH group. In addition, the clivarin-treated patients with positive AHPF4 antibodies were found to be predominantly of the non-functional type and were found in the order of IgM > IgA > IgG Together, these observations demonstrate that ELISA-detectable IgG subtype in UFH-treated patients may be more likely to cause functional/pathologic responses during HIT syndrome. Thus, determination of IgG subtype of AHPF4 antibodies during HIT syndrome may be crucial in the diagnosis; however, the relevance of the pathologically non-functional (IgA and/or IgM) antibodies and the overall mechanism(s) of these HIT-associatied antibodies need further investigation.

Anticoagulants↗

PubMed1994

Regulation of NMDA channel function by endogenous Ca(2+)-dependent phosphatase.

Protein kinases modulate the activity of several ligand-gated ion channels, including the NMDA (N-methyl-D-aspartate) subtype of glutamate receptor. Although phosphorylation and dephosphorylation of glutamate receptors may participate in several lasting physiological and pathological alterations of neuronal excitability, the physiological control of this cycle for NMDA channels has not yet been established. Using cell-attached recordings in acutely dissociated adult rat dentate gyrus granule cells, we now demonstrate that inhibitors of an endogenous serine/threonine phosphatase prolong the duration of single NMDA channel openings, bursts, clusters and superclusters. Okadaic acid, a non-selective phosphatase inhibitor, prolongs channel openings only at a concentration that inhibits the Ca2+/calmodulin-dependent phosphatase 2B (calcineurin), and is ineffective when Ca2+ entry through NMDA channels is prevented. Furthermore, FK506, an inhibitor of calcineurin, mimics the effects of okadaic acid. Thus in adult neurons, calcineurin, activated by calcium entry through native NMDA channels, shortens the duration of channel openings. Simulated synaptic currents were enhanced after phosphatase inhibition, which is consistent with the importance of phosphorylation of the NMDA-receptor complex in the short- and long-term control of neuronal excitability.

Animals↗

PubMed2001

Four different types of protease-activated receptors are widely expressed in the brain and are up-regulated in hippocampus by severe ischemia.

A variety of extracellular serine proteases are expressed in the central nervous system or might permeate the blood-brain barrier under pathological conditions. However, their intracerebral targets and physiological functions are largely unknown. Here, we show that four distinct subtypes of protease-activated receptors (PARs) are abundantly expressed in the adult rat brain and in organotypic hippocampal slice cultures. PAR-1 expression was significant in the hippocampus, cortex and amygdala. Highest densities of PAR-2 and PAR-3 were observed in hippocampus, cortex, amygdala, thalamus, hypothalamus and striatum. Apart from the striatum, a similar localization was found for PAR-4. Within the hippocampal formation, each PAR subtype was predominantly localized in the pyramidal cell layers. Additionally, we identified PAR-2 in mossy fibers between dentate gyrus and CA3, PAR-3 in the subiculum and PAR-4 in CA3 and in mossy fibres as well as in the stratum lacunosum moleculare. After exposing hippocampal slice cultures to a severe experimental ischemia (oxygen-glucose deprivation), the expression of PARs 1-3 was up-regulated with subtype-specific kinetics. The localization of PARs in brain regions particularly vulnerable to ischemic insults as well as distinct alterations in the expression pattern after experimental ischemia support the notion of an important role of extracellular serine proteases and PARs in cerebral ischemia.

Animals↗

PubMed1997

Headache in a population-based elderly cohort. An ancillary study to the Italian Longitudinal Study of Aging (ILSA).

The aims of this ancillary study to the Italian Longitudinal Study of Aging were: (1) to provide reliable prevalence data on headache in an elderly population, (2) to classify the subtypes of headache according to International Headache Society criteria, and (3) to identify possible risk factors and associated pathologies in the elderly. A total of 312 subjects were examined, 148 women and 164 men, with a mean age of 73 years (SD 5.5). For 236 subjects (75.7%), 141 men (85.9%) and 95 women (64.2%), headache had never been a problem; 57 subjects (18.3%), 21 men (12.8%) and 36 women (24.3%), reported troublesome headache only in the past. Nineteen subjects (6%), 6 men (3.6%) and 13 women (8.8%), reported current headache: in this group tension-type headache was the most prevalent, accounting for 2.6%; secondary headaches ranked second, accounting for 2.2%; and only 1% had current migraine. Our data indicate female sex and younger age as risk factors for headache, and associate migraine and secondary headaches with hypertension, tension-type headaches and secondary headaches with diabetes, and tension-type headaches with myocardial ischemia.

Age Factors↗

PubMed2000

Expression of the adrenomedullin gene in epithelial ovarian cancer.

Adrenomedullin (AM) gene expression was analysed in 60 cases of epithelial ovarian cancer, (29 serous, 14 mucinous, 13 endometrioid, three clear cell, and one undifferentiated) using reverse transcription-polymerase chain reaction (RT-PCR); 10 of the cases were of low malignant potential; 25 were stage I; three were stage II; 27 were stage III; and five were stage IV. The level of AM gene expression was described in terms of the relative yield of the AM gene to the beta2-microglobulin gene. AM gene expression ranged from 0.04 to 1.57 (median 0.36). The association between histological grade and AM gene expression was significant (P: = 0.027), however, the association with other clinico-pathological features, i.e. patients' age at diagnosis, stage of disease, residual tumour mass after initial surgery, and histological subtype were not significant. Survival data were available for all patients and univariate Cox regression analysis showed that the AM gene expression was significantly associated with a poor prognosis (P: = 0.019). Immunohistochemical studies showed that AM was localized in the outer cell membrane or the cytoplasm of the carcinoma cells and in the endothelial cells of the tumour stroma. The AM gene expression level may play a key role in the biology of epithelial ovarian cancer and may define a more aggressive tumour phenotype.

Adrenomedullin↗

PubMed1991

Sclerosing Sertoli cell tumor of the testis. A report of 10 cases.

Sex cord-stromal tumors of the testis are uncommon and have been less well characterized than similar tumors of the ovary, with a much greater proportion of them falling into the "unclassified" category. We report the clinical and pathological features of 10 Sertoli cell tumors of the testis with prominent sclerosis, representing a distinctive, heretofore undescribed subtype of Sertoli cell tumor in the human. The patients were mostly in their 3rd and 4th decades (median age, 30 years; range, 18-80 years). One tumor occurred in a cryptorchid testis, and one patient had had an orchidopexy several years prior to his presentation. There was no evidence of estrogen production by the tumor in any case. The tumors occurred equally often in each testis and were small (0.4-1.5 cm) in diameter, except for two tumors, which were 4.0 cm in diameter. All of them were centered in the testicular parenchyma and were well-demarcated, hard, yellow-white to tan nodules. They were characterized histologically by solid and hollow, simple and anastamosing tubules, large irregular aggregates, and thin cords of Sertoli cells in a prominent collagenous background. The tumor cells were of medium size and had pale cytoplasm, which sometimes contained large lipid vacuoles; the round nuclei varied from small and dark to large and vesicular. Follow-up information on five patients--including the only one whose tumor had malignant features histologically--showed no evidence of recurrence or metastasis 3-10 years (mean, 5.8 years) after orchidectomy alone.

Adult↗

PubMedDate not supplied

Orofacial pain--Part I: Assessment and management of musculoskeletal and neuropathic causes.

Orofacial pain is a common complaint, affecting the lives of millions of people around the world. Chronic orofacial pain often constitutes a challenging diagnostic problem that can be complicated by psychosocial factors and typically requires multidisciplinary treatment approaches. The fundamental prerequisite for successful management of orofacial pain is an accurate diagnosis. Generating a differential diagnosis, which will ultimately lead to a definite diagnosis, requires thorough knowledge of the diagnostic range of orofacial pain. There is a vast array of orofacial pain categories including: (1) musculoskeletal, (2) neuropathic, (3) vascular, (4) neurovascular, (5) idiopathic, (6) pain caused by local, distant, or systemic pathology, and (7) psychogenic. This article presents the salient clinical features and the therapeutic approaches for the various subtypes of musculoskeletal and neuropathic pain. Musculoskeletal pain is the most prevalent orofacial pain, with temporomandibular disorders and tension-type headache being the main examples. Neuropathic pain develops secondary to neural injury and/or irritation and can be distinguished into episodic, including trigeminal neuralgia and glossopharyngeal neuralgia, as well as continuous, such as herpetic and postherpetic neuralgia, traumatic neuralgia, and Eagle's syndrome.

Causality↗

PubMed2000

Risk factors and clinical manifestations of pre-eclampsia.

OBJECTIVE: To study associations between established risk factors for pre-eclampsia and different clinical manifestations of the disease. DESIGN: A population-based, nested case-control study. SETTING: Information from 12,804 consecutive deliveries that took place over three years at a birth clinic, which alone serves a population of nearly 240,000 in Rogaland county, Norway. SUBJECTS: Cases of pre-eclampsia (n = 323) and healthy controls (n = 650) were selected. Pre-eclampsia was defined as increase in diastolic blood pressure (> or = 25 mmHg to > or = 90 mmHg) and proteinuria (> or = 1+ by dipstick testing) after 20 weeks of pregnancy. MAIN STUDY MEASURES: Parity, previous pre-eclampsia, blood pressure, maternal weight, and maternal smoking were included as study variables. Women with pre-eclampsia were grouped according to clinical manifestations of the disease (i.e. severity [mild, moderate or severe]) and time of onset (early or late gestation). Associations with the study factors were estimated as relative risks (odds ratio, OR). RESULTS: Both nulliparity and hypertension increased pre-eclampsia risk, with no clear preference for any clinical subtype. High maternal weight was related to a higher risk of mild and moderate, but not severe, pre-eclampsia. Previous pre-eclampsia strongly increased the risk for pre-eclampsia in the current pregnancy, and the risk of early onset disease was especially high (OR 42.4; 95% CI 11.9-151.6). Overall, smoking was associated with a reduced risk for pre-eclampsia (OR 0.6; 95% CI 0.4-0.9). However, no effect of smoking was observed in the early onset disease group and among women with repeated pre-eclampsia. CONCLUSION: Nulliparity and hypertension increased the risk for each subgroup of pre-eclampsia, but high maternal weight, previous pre-eclampsia and smoking were not consistently associated with each clinical subtype. This observation may suggest that heterogeneous clinical manifestations of pre-eclampsia may be preceded by different pathological mechanisms.

Body Weight↗