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PubMed2004

Molecular and functional aspects of human cysteinyl leukotriene receptors.

The cysteinyl leukotrienes (cys-LTs), i.e. LTC(4), LTD(4) and LTE(4), trigger contractile and inflammatory processes through the specific interaction with cell surface receptors belonging to the purine receptor cluster of the rhodopsin family of the G protein-coupled receptor (GPCR) genes. Cys-LTs have a clear role in pathophysiological conditions such as asthma, allergic rhinitis and other nasal allergies, and have been implicated in a number of inflammatory conditions including cardiovascular and gastrointestinal diseases. Pharmacological studies have identified two classes of cys-LT receptors (CysLT(1) and CysLT(2)) based on their sensitivity to CysLT(1) selective antagonists, albeit there is evidence for additional subtypes. Molecular cloning of the human CysLT(1) and CysLT(2) receptors has confirmed both their structure as putative seven transmembrane domain G protein-coupled receptors and most of the previous pharmacological characterization. The rank order of potency of agonist activation for the CysLT(1) receptor is LTD4 > LTC4 > LTE4 and for the CysLT(2) receptor is LTC4 = LTD4 > LTE4. The CysLT(1) receptor is most highly expressed in spleen, peripheral blood leukocytes, interstitial lung macrophages and in airway smooth muscle. The CysLT(2) receptor is mostly expressed in heart, adrenals, placenta, spleen, peripheral blood leukocytes and less strongly in the brain. Gene cloning of CysLT(1) and CysLT(2) receptors has renewed the attention on the cys-LTs field and will, hopefully, encourage future studies on the regulation of CysLT receptors expression and the dissection of their signalling pathways. Furthermore, the peculiar pattern of expression of the two receptor subtypes will promote the discovery of new functions for cys-LTs in physiological and pathological conditions. Only CysLT(1) selective receptor antagonists have been described to date and are currently available for the treatment of asthma. Molecular cloning of different CysLT receptor subtypes will certainly foster the development of new selective antagonists based on molecular modelling studies.

Animals↗

PubMed2006

Relationship between somatostatin receptor subtype expression and clinicopathology, Ki-67, Bcl-2 and p53 in colorectal cancer.

AIM: To study the SSTR1, 2, 3, 4, 5 expression and their relationships with clinico-pathological factors, cell proliferation, Bcl-2 and p53 expression in colorectal cancer cells. METHODS: Immunohistochemical staining of five SSTR subtypes, Ki-67, Bcl-2 and p53 was performed by the standard streptavidin-peroxidase (SP) technique for the paraffin sections of 127 colorectal cancers. and expression of five SSTR subtypes in 40 specimens of normal colorectal mucosae was detected with the same method. RESULTS: Positive staining for five SSTR subtypes was observed in colorectal cancer cells and normal colorectal mucosae. SSTR1 was the most predominant subtype in both colorectal cancer and normal colorectal mucosa, and the second was SSTR5 or SSTR2. As compared with normal colorectal mucosa, SSTR4 was more frequently expressed in colorectal cancer cells (2.5% vs 18.9%, P<0.05); the expression of SSTR2, 4, 5 in moderately to well differentiated colorectal adenocarcinoma was significantly higher than that in poorly differentiated ones (P<0.05), the SSTR1 expression in colorectal cancer with positive lymph node metastasis was significantly higher than that with negative lymph node metastasis (72.2% and 54.5%,P<0.05). In addition, in the ulcerative type of colorectal cancer, SSTR2 expression was obviously decreased (P<0.05); the correlation did not reach a statistical significance between the five SSTR subtypes expression and Dukes'stages (P>0.05), but the frequency of SSTR1 expression increased with Dukes'stage, while SSTR3 and SSTR5 expression decreased with Dukes' stage. Moreover, there was no correlation between expression of the five SSTR subtypes and other clinicopathological factors such as age, sex, tumor site, tumor depth, distant metastasis. The proliferative indexes in colorectal cancer cells with negative expression of SSTR2 and SSTR3 were significantly higher than that with positive expression (P<0.05). The Bcl-2 expression in colorectal cancer cells with positive expression of SSTR1, 2, 3, 5 was significantly lower than that with negative expression (P<0.05). There was no correlation between five SSTR subtypes and p53 expression. CONCLUSION: The most predominant SSTR subtype is SSTR1, and the second is SSTR2 or SSTR5. Five SSTR subtypes play different roles in the development of colorectal cancer. SSTR2 and SSTR3 can inhibit the proliferation and promote apoptosis of tumor cells.

Adult↗

PubMed2002

Demonstration of de novo HIV type 1 production by detection of multiply spliced and unspliced HIV type 1 RNA in paraffin-embedded tonsils.

HIV-1 infection of tonsils takes place when virus spreads systemically, and may occur when tonsillar tissue serves as the initial portal of HIV-1 entry. The HIV replication cycle includes the production of regulatory and accessory gene mRNAs, produced by splicing of genomic mRNA, that are hallmarks of de novo virus production. We sought to demonstrate, for the first time, the presence of multiply spliced viral RNA transcripts in archival tissue as a marker for active virus replication. Further, amplified cDNA sequences from unspliced pol gene mRNA were used to define the genetic subtype of HIV-1 within these tissues. RNA was extracted from surgical pathological, formalin-fixed, paraffin-embedded specimens, and RT-PCR was performed with primers for unspliced and multiply spliced HIV-1 transcripts. Amplification products were analyzed by agarose gel electrophoresis and their specificity was confirmed by sequencing and Southern blot hybridization. Unspliced HIV-1 pol transcripts yielded cDNA amplicons of 184 base pairs (bp) that were cloned and sequenced. Phylogenetic analysis revealed these sequences to be of HIV-1 subtype B. Multiply spliced transcripts specific for the tat/rev (173 bp), tat (268 bp), and tat/rev/nef (146 bp) regulatory gene mRNAs could be demonstrated in all cases. These results support the demonstration of active replication of HIV-1 in archival tonsillar tissues previously shown by p24 antigen staining. They also show the feasibility of performing molecular epidemiologic studies on HIV-1 cDNA sequences from archived pathologic specimens.

Base Sequence↗

PubMed2005

Physiology and pathology of NMDA receptors.

Ionotropic glutamate receptors of the N-methyl-D-aspartate (NMDA) subtype are highly expressed in the central nervous system and are involved in excitatory synaptic transmission and synaptic plasticity. Prolonged activation of NMDA receptors can lead to excitotoxicity, which is implicated in the pathogenesis of neurodegeneration occurring in various acute and chronic disorders of the central nervous system. Recent advances in understanding the function, pharmacology, genetics and structure of NMDA receptors has promoted a search for new compounds that could be therapeutically used. These compounds act on agonist binding sites, either apart from them or directly within the ion channel pore. Members of the last group are called open channel blockers, and some of them, such as memantine and ketamine, are already clinically used. Kinetic modeling of NMDA receptor activity was employed to define the effects of various groups of modulators. Quantifying the action of these substances by kinetic parameters can help us to reveal the molecular mechanism of action at the receptor and to characterize the dependence of its action on the mode of NMDA receptor activation. Two modes are considered: phasic activation, induced by synaptically released glutamate, and tonic activation, which is expected to occur under pathological conditions when low, but sustained levels of glutamate activate NMDA receptors. The aim of our review is to summarize the recent data about the structural and functional properties of NMDA receptors and their role in long-term potentiation and excitotoxicity.

Animals↗

PubMed2000

Dopamine D(1) and D(2) receptors in the forebrain of dystonia musculorum mutant mice: an autoradiographic survey in relation to dopamine contents.

Dystonia musculorum (dt(J)/dt(J)) mutant mice suffer from a degeneration of spinocerebellar tracts as well as a dystrophy of peripheral sensory tracts. This neurological mutant has been proposed as an animal model of human cerebellar ataxia, in particular of the Friedreich's type; thus, it was deemed of interest to examine the endogenous contents of dopamine (DA) and metabolites as well as the distribution of DA receptors of the D(1) and D(2) subtypes, in order to delimit the biochemical characteristics of this pathological disorder, and determine an eventual dopaminergic dysfunction in this mutant. Tissue DA and its major metabolites 3, 4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine were measured by HPLC coupled to electrochemical detection in six cortical regions, in four divisions of rostral neostriatum and two halves of caudal neostriatum, as well as in olfactory bulb, nucleus accumbens, septum, amygdala, hippocampus, thalamus, hypothalamus, brainstem, cerebellum, substantia nigra, and ventral tegmental area. The only significant difference between dt(J)/dt(J) mice and wild-type controls was an increase in hypothalamic DA contents (+47%). Quantitative autoradiography with [(3)H]SCH23390 and [(3)H]raclopride, to label D(1) and D(2) receptors, respectively, revealed only moderate changes in receptor densities in a few localized regions. In dt(J)/dt(J) mutants, D(1) receptor numbers were found to be higher in thalamus (+27%) as well as in the medio-dorsal (+16%) and in the latero-dorsal (+16%) quadrants of rostral neostriatum, while D(2) receptor densities were greater in the medio-ventral (+32%) and the latero-dorsal (+17%) quadrants. The present results indicate an overall conservation of dopaminergic functions, albeit the few localized sites of increased D(1) and D(2) receptor densities, and that are seemingly independent of the DA innervation pattern, as revealed by the tissue measurements of DA and metabolites. They also rule out a major pathology linked to deficits in DA neurotransmission, and validate this mutant as an animal model of human cerebellar ataxia, probably of the Friedreich type.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1978

Extraskeletal Ewing's sarcoma: a preliminary review of 26 cases encountered in the Intergroup Rhabdomyosarcoma Study.

Twenty-six of three hundred and fourteen (26/314) patients whose tumors were reviewed by the Pathology Evaluation Committee of the Intergroup Rhabdomyosarcoma Study have histologic subtypes I and II which have morphologic characteristics similar to Ewing's sarcoma of bone. They are somewhat more common in an extremity lesion but have no relation to patient age. Disease-free survival is good; seventeen of twenty-six (17/26) or sixty-five (65%) percent thus far.

Child↗

PubMed2005

Proliferation and progesterone receptor status in benign meningiomas are not age dependent.

BACKGROUND: Some authors have suggested that the biology of meningiomas differs according to a patient's age. Proliferation, vascularity, and hormonal status in meningiomas can be used to describe changes during aging. In the current study, proliferation activity with the Ki-67/MIB-1 antibody was evaluated by immunohistochemistry in meningioma tissue specimens from young and elderly patients. METHODS: Over the past 25 years, tissue samples from 1766 patients with meningiomas were evaluated. Of these, 588 tumor specimens from 554 patients who underwent surgery between 1990 and 2000 were evaluated immunohistochemically. The proliferation index (LI) and progesterone receptor (PR) in meningiomas were quantitatively estimated in elderly (age > or = 70 years) and young patients (age < 70 years). Patients' charts including surgical records, discharge letters, pathology reports, and imaging studies were reviewed. Correlations with histologic subtype, disease recurrence-free survival, resection grade, location, size, vascularity, and tumor calcification were calculated as well. Only patients with a well documented follow-up were included in the statistical evaluation (n = 385). RESULTS: Compared with the young group of 344 patients with meningioma (age < 70 years; mean age, 51.9 years; range, 18-69 years), the elderly population (age > or = 70 years; n = 41; mean age, 74.9 years; range, 70-88 years) showed a male-to-female ratio of 3.2: 1. Both groups had an identical median Ki-67 LI of 3.0% and a PR status of 56.1% versus 58.4 %. No statistically significant differences in disease recurrence-free survival could be found in the two groups. CONCLUSIONS: Proliferation rates and PR status in benign intracranial meningiomas did not appear to be age dependent.

Adolescent↗

PubMedDate not supplied

Contrast-enhanced MR imaging of intrahepatic cholangiocarcinoma: pathologic correlation study.

The authors describe the enhanced magnetic resonance (MR) imaging appearance of intrahepatic cholangiocarcinoma. The MR images of eight patients with intrahepatic cholangiocarcinoma who underwent MR examination within 3 weeks before partial hepatectomy were retrospectively studied. The MR images, including a dynamic study, were compared directly with pathologic and histologic findings. The peripheral region of the medullary subtype of cholangiocarcinoma, with many tumor cells, showed greater enhancement relative to liver parenchyma in the early phase. The peripheral region of the scirrhous subtype, with fewer tumor cells showed less enhancement in the early phase. In one patient, the thin rim of the medullary tumor showed less enhancement in the late phase, and this rim corresponded to the peripheral region of the medullary tumor with many tumor cells. The central region of tumors with a large amount of fibrous tissue showed prolonged enhancement in the late and delayed phases. The thin rim of liver parenchyma around the tumor showed less enhancement in the early phase and greater enhancement in the late phase; this rim corresponded to congestive liver parenchyma with dilated sinusoids. Intrahepatic cholangiocarcinoma shows various enhancement patterns, which depend on both the histologic subtype and the degree and distribution of fibrosis within the tumor.

Aged↗

PubMed1994

Protection of mice against an influenza virus infection by oral vaccination with viral nucleoprotein incorporated into immunostimulating complexes.

Influenza A virus nucleoprotein (NP) was integrated into immunostimulating complexes (ISCOMs) after attachment of bacterial lipopolysaccharide to the antigen. Oral immunization with these NP-ISCOMs protected mice fully against an otherwise lethal challenge infection with an unrelated influenza virus subtype without the appearance of severe clinical signs or extensive pathological lesions in the lungs. Mice immunized with analogous bovine serum albumine-incorporated ISCOMs all died. After oral immunization, high titers of NP-specific antibodies, particularly IgA, could be detected in the bronchoalveolar fluid and in the blood serum. No cytotoxic lymphocytes could be demonstrated in the spleens or the lungs of vaccinated mice, and no anti-NP antibody-dependent cytolysis of infected host cells was mediated by complement or in the form of an antibody-dependent cell cytotoxicity. However, a vigorous delayed-type hypersensitivity reaction was produced after probing vaccinated animals with purified NP. No comparable protective immunity or antibody response was induced by a strictly intragastric administration of NP-ISCOMs. It appears, therefore, that the general and local immune response in the lungs was primarily stimulated through contact of NP-ISCOMs with the mucous membrane of the oro-pharyngeal cavity and that cytotoxic effects did not play a major role for the establishment of the protective immunity. Partial protection against a lethal challenge was observed in chickens immunized with NP-ISCOMs in the drinking water.

Administration, Oral↗

PubMed2006

[Requirements for the development of molecularly defined targeted therapy in oncology].

BACKGROUND: The revolutionary development in the biosciences during the last 15 years--including the sequencing of the human genome and multiple other genomes as well the possibility of massive parallel analysis of thousands of data points within a single experiment--have greatly improved our understanding of the pathophysiology of tumor development and progression as well as metastasis. THE CURRENT SITUATION: The further development of genomic technology for routine clinical use is slowly but steadily leading to a paradigm shift: the currently used tumor definition based on pathologic and histological assessment is replaced by molecularly defined tumor subtypes. This is an essential prerequisite for the development of molecularly defined individualized therapies in oncology leading to more effective treatments with less severe side effects. The first molecularly defined drugs (targeted drugs) have already entered the clinical arena. However, not only diagnostics and therapy on oncology will change dramatically in the future, but also the way we have to organize oncology itself. OUTLOOK: The integration of genomics and information technologies will require the establishment of interdisciplinary teams beyond the already established collaborations between surgeons, radiotherapists and medical oncologists.

Algorithms↗

PubMed2001

Ataxin-7 expression analysis in controls and spinocerebellar ataxia type 7 patients.

Expansion of polymorphic CAG repeats encoding polyglutamine cause at least eight inherited neurodegenerative diseases, including Huntington disease and the spinocerebellar ataxias. However, the pathways by which proteins containing expanded polyglutamine tracts cause disease remain unclear. To gain insight into the function of the SCA7 gene product, ataxin-7, as well as its contribution to cell death in spinocerebellar ataxia type 7 (SCA7), polyclonal antibodies were generated and ataxin-7 expression was examined within neuronal tissues from controls and three SCA7 patients. Immunoblotting demonstrates that ataxin-7 is widely expressed but that expression levels vary between tissues. Immunohistochemical analyses indicate that ataxin-7 is expressed within neurons both affected and unaffected in SCA7 pathology and that subcellular localization varies depending upon the neuronal subtype. Additionally, ataxin-7 staining was detected throughout control retina, including intense staining within the cell bodies and photosensitive outer segments of cone photoreceptors. Anti-ataxin-7 antibodies revealed intranuclear inclusions within surviving inferior olivary and cortical pyramidal neurons, as well as within surviving photoreceptor and ganglion cells of SCA7 patients harboring either 42 or 66 CAG repeats at the SCA7 locus. In contrast, inclusion formation was not detected within neurons of a patient with 41 repeats. This study broadens the current understanding of ataxin-7 localization and incorporates for the first time analysis of late-onset SCA7 patients where polyglutamine tract lengths are relatively shorter and disease course less severe than in previously described infantile-onset cases.

Aged↗

PubMed2005

Progressive morphometric and cognitive changes in vascular dementia.

Evidence for progressive cognitive decline in vascular dementia (VaD) is mixed, with some studies showing little or no decline over time. One possible explanation for these inconsistent findings is the heterogeneity of pathology encompassed by the VaD diagnosis. It is possible that subtypes of VaD (i.e. those resulting from different lesion distributions) show different patterns of cognitive decline. In the present study, a heterogeneous VaD group demonstrated cognitive decline from baseline to 12-month follow-up. Although this decline was coincident to morphometric changes (i.e. increased subcortical hyperintensities (SH), decreased whole brain volume (WBV)), no relationship emerged between cognitive decline and morphometric changes. Preliminary examination of VaD subtypes revealed patients with subcortical infarct or SH-only exhibited greater decline than VaD patients with cortical lesions. Further research is needed to determine whether this observed decline is attributable to differential lesion distribution or statistical artifact.

Aged↗

PubMed2003

Synthesis and beta-blocking activity of (R,S)-(E)-oximeethers of 2,3-dihydro-1,8-naphthyridine and 2,3-dihydrothiopyrano[2,3-b]pyridine: identification of beta 3-antagonists.

Drugs acting on beta(1)- and beta(2)-adrenergic receptors are widely used for the clinical management of a large number of cardiovascular and respiratory pathologies. In the last decade, the discovery of the third subtype of beta receptors, the beta(3)-adrenoceptor, gave a further pharmacological target for the development of new selective drugs. Initially, a potential therapeutic use of beta(3)-selective agents seemed to be restricted to agonists, for the treatment of metabolic diseases, such as obesity, non-insulin-dependent diabetes, urinary frequency and incontinence. More recently, some interesting theories about a negative role played by the cardio-depressant activity of myocardial beta(3)-adrenoceptors in heart failure, seemed to justify a clinical use of beta(3)-antagonists in the last phases of this cardiac disease. Following the indications deriving from previous experimental work, the beta-antagonist properties of newly-synthesised (R,S)-(E)-oximeethers of 2,3-dihydro-1,8-naphthyridine and of 2,3-dihydrothiopyrano[2,3-b]pyridine were evaluated, in order to identify some useful structure-activity relationships, which might account for selectivity towards the three beta-subtypes and, in particular, the beta(3)-adrenoceptor. Among the various observations regarding possible structure-activity relationships, able to explain the pharmacodynamic patterns of the synthesised compounds on the three subtypes of beta-adrenoceptors, the most significant data derived from the evaluation of the beta(3)-blocking properties of some oximeethers of 1,8-naphthyridine derivatives. In these molecules, although the presence of the large substituents in position 7, such as 4-chloro-phenoxy- or 4-t-butyl-phenoxy groups determined a dramatic decline in both the beta(1)- and beta(2)-activities, this structural characteristic had a modest influence on the beta(3)-affinity, which was only slightly lower. Hence, this last structural requirement of oximeethers of 1,8-naphthyridine derivatives seems to represent a useful expedient to induce an appreciable selectivity towards the beta(3)-receptor, through a markedly negative effect on the beta(1)- and beta(2)-activities rather than an increase in the beta(3)-affinity.

Adrenergic beta-Antagonists↗

PubMed2002

The relationship of thought-action fusion to pathologicial worry and generalized anxiety disorder.

Meta-cognitive beliefs associated with pathological worry and generalized anxiety disorder (GAD) may encompass the likelihood subtype of thought-action fusion (TAF), the belief that one's thoughts can influence outside events. In the current study of 494 undergraduate college students, positive correlations between scores on the Penn State Worry Questionnaire (PSWQ) and the two Likelihood subscales of the TAF Scale were found, and participants endorsing at least some DSM-IV diagnostic criteria for GAD scored significantly higher on both TAF-Likelihood subscales than participants reporting no GAD symptoms. However, these TAF scales did not predict GAD diagnostic status with PSWQ included as a predictor. In contrast to previous research, the TAF-Moral scale did not correlate with worry. Relationships between TAF, pathological worry, and meta-cognition are discussed in relation to GAD.

Adult↗

PubMed1998

Unicystic ameloblastoma. A review of 193 cases from the literature.

Based on a world-wide literature survey of 193 published cases of unicystic ameloblastomas (UA), data have been produced allowing the presentation of a revised concept of this much debated lesion. UA is a variant of the solid or multicystic ameloblastoma. Radiographically, the unilocular pattern is more common that the multilocular, especially in cases associated with tooth impaction. However, it is stressed that although the lesion is pathomorphologically unicystic, it will far from always produce a unilocular radiolucency. The mean age at the time of diagnosis of UA is closely related to an association with an impacted tooth. Almost 20 years separate the mean age of the 'dentigerous' variant from the 'non-dentigerous' (16.5 years versus 35.2 years) The male:female ratio for the 'dentigerous' type is 1.5:1, but for the 'non-dentigerous' type it is reversed (1:1.8). Location favours greatly the mandible (mandible to maxilla = 3 to 13:1). Between 50 and 80% of cases are associated with tooth impaction, the mandibular third molar being most often involved. The 'dentigerous' type occurs on average 8 years earlier than the 'non-dentigerious' variant. The mean age for unilocular, impaction-associated UAs is 22 years, whereas the mean age for the multilocular lesion unrelated to an impacted tooth is 33 years. Histologically, the minimum criterion for diagnosing a lesion as UA is the demonstration of a single cystic sac lined by odontogenic (ameloblastomatous) epithelium often seen only in focal areas. This simple type of UA (according to the authors' modification of the classification by Ackermann et al. (Journal of Oral Pathology 1988; 17:541-546)), is one of four UA subtypes, the others being (1) simple with intralumenal proliferations; (2) simple with both intralumenal and intramural proliferations; and (3) simple with intramural proliferations only. All four subtypes occur in both the 'dentigerous' and 'non-dentigerous' variants. The simple subtype with and without intralumenal proliferations may be treated conservatively (enucleation), whereas subtypes showing intramural growths must be treated radically, i.e. as a solid or multicystic ameloblastoma. Finally, the authors disclose areas and issues pertaining to UA that still need to be addressed.

Age Factors↗

PubMed2001

CD10 and Bcl10 expression in diffuse large B-cell lymphoma: CD10 is a marker of improved prognosis.

AIMS: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically and pathologically heterogeneous. The Bcl10 gene was recently isolated from the breakpoint region of t(1;14)(p22;q32) in mucosa-associated lymphoid tissue (MALT) lymphomas, and is considered to be an apoptosis-associated gene. CD10 is considered to be a marker of follicular centre B-cell differentiation. To assess the clinical significance and roles of CD10 and Bcl10 in DLBCL, we analysed 138 cases, using immunohistochemical methods. METHODS AND RESULTS: CD10 expression was limited to the cytoplasm, whereas Bcl10 expression was detected in the cytoplasm and/or nuclei. CD10 expression was detected in 39 of 138 cases (28.2%), cytoplasmic Bcl10 in 68 cases (49.2%), and nuclear Bcl10 in 34 cases (24.6%). Nuclear Bcl10 was detected in 14 of 28 cases (50%) of extranodal DLBCL, but only 20 of 110 cases (18.2%) of nodal DLBCL. Cytoplasmic Bcl10 was detected in 19 of 28 cases (67.8%) of extranodal DLBCL and 49 of 110 cases (44.5%) of nodal DLBCL. CD10 expression closely correlated with improved survival (68% overall survival (OS) vs. 48% OS), but not with site of disease. A high International Prognostic Index (IPI) was considered to be a poor prognostic factor associated with a shorter OS. CD10 expression was detected in 27 of 84 cases (32.1%) with low-risk IPIs, and in 12 of 54 cases (22.2%) with high-risk IPIs. In the low-risk group, cases expressing CD10 carried a better prognosis than CD10- cases (93% OS vs. 71% OS), whereas this was not the case in the high-risk group (25% vs. 20%). CONCLUSIONS: Bcl10 expression was associated with extranodal DLBCL, but not with prognosis. CD10 expression was closely associated with improved survival, but not with risk as predicted by IPI. Overall, our results suggest that CD10 expression may be useful, in combination with clinical parameters, for determining the prognosis of DLBCL.

Adaptor Proteins, Signal Transducing↗

PubMed2003

Diagnosis and management of stage I/II melanoma.

OBJECTIVES: To describe the clinical features and histologic subtypes of cutaneous melanoma; to review the diagnosis, clinical, and pathologic staging of melanoma and the associated prognostic factors; and to review the treatment and management of AJCC stage I and II melanoma. DATA SOURCES: Scientific and review articles, textbooks, and clinical practice. CONCLUSIONS: Management of melanoma depends on accurate diagnosis, staging, and interpretation of prognostic factors. The treatment of choice for stage I and II melanoma is surgery, ranging from simple excision to lymph node dissection. IMPLICATIONS FOR NURSING PRACTICE: Familiarity with the clinical features of melanoma assists nurses in the screening and early detection of melanoma. Knowledge of AJCC staging guides education regarding treatment and lifelong surveillance.

Diagnosis, Differential↗

PubMed1998

Idiopathic copper toxicosis.

Liver diseases of infancy and childhood are generally rare and within the spectrum of these disorders, only a few subtypes are related to abnormal hepatic copper accumulation. Idiopathic copper toxicosis has been defined as such a subtype; although this disease is characterized by distinct clinical and pathologic features, its exact etiology is still controversial. On the basis of a review of the literature, supplemented by our own observations of 138 cases endemic to western Austria, we hypothesize that idiopathic copper toxicosis is caused by a synergy of an autosomal-recessive inherited defect in copper metabolism and excess dietary copper. Increased awareness of the disease should enable early diagnosis and lead to successful treatment, thereby improving the overall poor prognosis of affected patients.

Child, Preschool↗