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PubMed1990

[The clinical characteristics of treatment-resistant forms of lymphogranulomatosis in children].

Results of treatment of 406 primary cases of Hodgkin's disease aged 2-15 years were retrospectively analysed. Complete remission was registered in 349 (86.0%) patients whereas in 57 (14.0%) partial or no response was observed (resistant forms). The characteristic features of the latter group were: age 10-14 years, short history of disease, primary involvement of the mediastinum, lymphocyte depletion histologic subtype, stage IV, presence of B-symptoms and biologic signs of activity, involvement of mediastinal and bronchopulmonary lymph nodes, 7-9 pathologic sites and bulky (larger than 5 cm in diameter) lesions. Six or more of the above features were observed in 89.5% of resistant patients and as few as 2.6% of complete responders.

Adolescent↗

PubMed1978

[Immunological problems of influenza virus infections].

Reference is made to results reported in literature as well as to some of the author's own findings for a summary account of specific immune responses to influenza virus infections. Some introductory comments on the correlations that exist between morphology and function of structural components of the influenza virus as well as on the pathogenesis and its relevance to the immunological responses are followed by a description of the humoral immune response. An assured correlation has been found to exist between the titres of hemagglutination-inhibiting antibodies with responses specific of subtypes and of strains for the protection against homologous influenza virus infection in terms of prevention of outbreak or mitigation of the pathological course. Anti-neuraminidase antibodies have influence upon virus expansion in the organism and in the given population as well as upon the severity of the disease. Particular importance has been attributed to the secretory immunoglobulins. Used in conjunction with interferone, they obviously had an infection-preventing function, wheras the primary role of serum anibodies was a reduction of severity. The studies into cell-mediated immune responses were much less intensive than those conducted into antibody formation. Cell-mediated immune response is thought to emanate from induction of hemagglutinin and is directed against the latter. Sufficient results have not become available as yet on the importance of cellular immune response to protection.

Animals↗

PubMed1993

Metastatic cystosarcoma phyllodes associated with paraplegia: an uncommon complication of an uncommon tumor.

Cystosarcoma phyllodes is a rare form of breast cancer that rarely metastasizes. This case represents the first reported case of a pathological spine fracture and neurologic injury as a result of metastatic cystosarcoma phyllodes. Physicians should be aware of a recently identified histological subtype of cystosarcoma that exhibits an increased incidence of hematogenous metastasis.

Adult↗

PubMed1998

Downregulation of thyroid hormone receptor subtype mRNA levels by retinoic acid in cultured cardiomyocytes.

The thyroid hormone receptors (TR) and the retinoic acid receptors share a high degree of homology and their signaling pathways interplay. Thyroid hormone (T3) is known to be associated with various pathological heart conditions. Retinoids are known to ameliorate symptoms in hyperthyroid patients. The aim of this study was to investigate if retinoic acid (RA) can have any effects on TR in cardiac cells and thus play a role in heart disease. Confluent AT-1 cardiomyocytes were treated with RA, T3 depleted medium and DITPA (a cardiotonic T3 analogue) for 48 hours. Solution hybridization for the determination of mRNA for TR alpha 1, alpha 1, beta 1 and beta 2 was performed. RA, T3 and DITPA significantly downregulated the alpha 1, beta 1 and beta 2. The T3 depleted medium did not affect the TR subtypes. The specificity of the solution hybridization method was tested by an RNase protection assay. In conclusion, RA downregulates TR in a similar way as T3 in cardiac cells, indicating a role for RA in thyroid associated heart disease.

DNA Probes↗

PubMedDate not supplied

Clinical and pathological features of 14 non-Hodgkin's lymphomas associated with coeliac disease.

BACKGROUND: It is well established that enteropathy associated T-cell lymphoma is associated with malabsorption which is due to gluten sensitivity (coeliac disease). Our study was performed to define the clinical features, histological subtypes, response to treatment, and outcome of the association of coeliac disease and T-cell lymphoma. PATIENTS AND METHODS: A retrospective study was performed in the UCL Group of Hematology to collect data on patients with a diagnosis of non-Hodgkin's lymphoma and coeliac disease. Fifteen cases were observed between 1985 and 1999. Case records for all but one patient were available and the pathological specimens of 14 patients were reviewed by two pathologists. RESULTS: Six previously diagnosed coeliac patients developed lymphoma; interval between coeliac symptoms and onset of the lymphoma ranged from 2 to 48 years (median 16 years). Five patients had coeliac disease and non-Hodgkin's lymphoma diagnosed concomitantly or less than 6 months before the symptoms leading to the diagnosis of lymphoma. Three patients had the diagnosis of coeliac disease after lymphoma diagnosis (1, 8 and 10 years later respectively). Ten non-Hodgkin's lymphomas were of T-cell origin and 4 were B-cell lymphomas. Eight out of 14 presented on a surgical emergency. Thirteen were treated using chemotherapy. The median survival from the diagnosis of enteropathy associated T-cell lymphoma was 12 months (range 1-126). CONCLUSIONS: Lymphomas associated with coeliac disease are heterogeneous and their diagnosis is difficult. The enteropathy-associated T-cell lymphoma is the most frequent, aggressive and fatal complication of coeliac disease but it is not rare to observe association with B-cell lymphoma. Chemotherapy is highly toxic in those patients. Despite a poor prognosis, long-term survival can be expected in a fraction of these patients.

Adult↗

PubMed1987

[Predictive value of additional immunohistochemical studies in histological diagnosis].

No exact information exists on the diagnostic value of immunohistochemistry applied to the routine material of an institute of surgical pathology. For this reason 390 cases additionally investigated by immunohistochemistry were analyzed retrospectively. This method was applied to 0.5% of all biopsies studied morphologically. On average 4.4 antisera per case were used. 352 cases (90.3%) initially diagnosed by morphology alone (16 benign lesions of debatable type, 111 lesions not clearly defined as benign or malignant, 225 malignant tumours of unknown subtype) could be clarified by immunohistochemistry. To obtain reliable results specific application of immunohistology and a clearcut formulation of the question are necessary. If these criteria are fulfilled immunohistochemistry represents a powerful tool in surgical pathology.

Adolescent↗

PubMed1996

Is there a therapeutic future for "potassium channel openers'?

1. Potassium channels, which control cell electrical activity, are among the most regulated of all ion channels in biology. Promotion of activity in K+ channels by a wide range of physiological factors tends to stabilize cell function. 2. The discovery of synthetic molecules (e.g. cromakalim) that 'directly' open ATP-sensitive K+ channels has led to a new direction in pharmacology. ATP-sensitive K+ channel-opening properties have subsequently been demonstrated in a diverse range of chemical structures (synthetic and endogenous). 3. The existence of so many different subtypes of K+ channels has been an impetus in the search of new potassium channel openers with different channel selectivities and thus biological profiles. 4. The decrease in cell excitability following K+ channel opening implies a broad clinical potential in a number of pathological conditions for K+ channel openers. Preclinical and clinical evidence supports therapeutic roles of K+ channel openers in disorders of a wide range of biological cells. 5. Although lack of selectivity of current compounds remains a major hurdle, advances in K+ channel openers and K+ channel pharmacology are encouraging. Differences already observed in the pharmacology of K+ channel openers are important factors for the development of second-generation compounds, when tissue selectivity is sought. 6. The availability of subtype-selective K+ channel openers will facilitate detailed study, through a combined effort of electrophysiology, functional pharmacology and molecular biology, leading to focused therapeutic approaches for defined pathological conditions.

Adenosine Triphosphate↗

PubMed1998

Reliability of a Crohn's disease clinical classification scheme based on disease behavior.

Classification of Crohn's disease (CD) by disease behavior--either inflammatory (INF), fibrostenotic (FS), or fistulizing/perforating (FP)--has been proposed as a means of assisting management decisions and predicting outcomes for subgroup analysis in clinical trials and for making phenotype/genotype associations in molecular genetic studies. Accurate and reproducible classification of CD patient subgroups is of paramount importance in such studies but to be useful, the classification scheme must have good interrater agreement. We sought to assess the interrater agreement associated with the disease-behavior classification scheme of CD. Twelve patients with CD were randomly selected from a database of 964 patients with CD undergoing medical or surgical treatment or both. Clinical details of the 12 cases, along with their radiographs and surgical and pathological reports, were presented to a panel of 20 experts who were asked to classify each case based on the patient's overall disease course (scenario A) and as if the patient were being entered into a clinical trial on that day (scenario B). Calculations of strength of interrater agreement were made and were expressed as the kappa statistic (kappa), with kappa < 0.2 = poor strength of agreement; kappa 0.21 - 0.4 = fair; kappa 0.41 - 0.6 = moderate; kappa 0.61 - 0.8 = good; and kappa 0.81 - 1.0 = very good. Five panel participants did not complete the study, and three clinical vignettes were excluded because of incomplete scoring, leaving a total of 15 panel experts assessing nine cases. Overall interrater agreement was only fair with kappa = 0.353 for scenario A and kappa = 0.291 for scenario B. Interrater agreement was less when only the most straightforward case in each disease category was evaluated. Classification of CD by pattern of disease behavior yields only fair interrater agreement. This raises concerns regarding its applicability, particularly in ongoing studies of genotype/phenotype associations. Further refinement of disease subtypes and clear operational definitions are required.

Adult↗

PubMed1990

Tumor cell concentration and tumor burden in relation to histopathologic subtype and other prognostic factors in early stage Hodgkin's disease. The Danish National Hodgkin Study Group.

Prognostic factors were examined by multivariate analysis after a recent follow-up of the 300 patients with Hodgkin's disease pathologic stage (PS) I or II treated with radiotherapy +/- adjuvant combination chemotherapy in the prospective randomized trial of the Danish National Hodgkin Study. Initial biopsy material was classified according to the Rye histopathologic classification, the grading and subclassification proposed by the British National Lymphoma Investigation (BNLI), and tumor cell concentration in sections. Tumor cell concentration as a prognostic factor turned out to be better than the other classifications. However, if macroscopic tumor burden was taken into account both tumor cell concentration and the other histopathologic classification systems lost their prognostic significance. Significantly, however, a combination of macroscopic tumor burden and tumor cell concentration, yielding an estimate of the total tumor cell burden, was even better than the macroscopic tumor burden as a prognostic factor. In conclusion, a simple tumor cell concentration count seems to be the most useful form of histopathologic subtyping for prognostic purposes in early stage Hodgkin's disease.

Hodgkin Disease↗

PubMed1998

Correlation of the immunohistochemical reactivity of mucin peptide cores MUC1 and MUC2 with the histopathological subtype and prognosis of gastric carcinomas.

The expression of MUC1 and MUC2 mucin peptide core antigens in gastric carcinomas was studied by immunohistochemistry to determine correlations with TNM stage and histo-pathological classifications as well as a possible prognostic impact. Paraffin-embedded specimens from 128 gastric carcinomas with a minimal follow-up of 5 years were immunostained. In addition to a polyclonal antiserum generated against polymorphic epithelial mucin (MUC1) from human milk, 2 monoclonal antibodies (MAbs), HMFG2 (anti-MUC1) and 4FI (anti-MUC2), were applied. Reactivity of carcinomas was correlated with the classifications of the UICC (TNM), WHO and Laurén. Correlations with overall survival were analyzed using the Kaplan and Meier product limit method. MUC1 immunoreactivity was associated with an advanced pTNM stage. The demonstration of both mucin species (MUC1, MUC2) displayed a statistically significant correlation with tubular/papillary vs. signet-ring cell differentiation as well as with intestinal-type vs. diffuse-type of tumor growth according to Laurén. In particular, MUC2 was only rarely detectable in signet-ring cell and diffuse-type tumors. MUC1 correlated with poor prognosis in all cases and the subgroup of stage I tumors. According to the histopathological classifications, a similar result was observed in signet-ring cell and diffuse-type carcinomas. In contrast, MUC2 reactivity was associated with a favourable prognosis of intestinal-type carcinomas. In the non-neoplastic gastric mucosa, both peptide cores were recognized in the superficial epithelium, whereas parietal cells contained only MUC1, and intestinal metaplasia almost exclusively MUC2 antigens. We conclude that the mucin peptide core antigens are suitable markers for the tubule-rich gastric carcinomas, which may in part be derived from intestinal metaplasia. In addition, MUC1 may exert a prognostic relevance and appears to be involved in the progression of diffuse-type tumors.

Adult↗

PubMed2003

Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene.

The cribriform-morular variant (C-MV), an unusual and peculiar subtype of papillary thyroid carcinoma (PTC), has been observed frequently in familial adenomatous polyposis (FAP)-associated thyroid carcinoma and also in sporadic thyroid carcinoma. In this paper, five young women with the C-MV of PTC, aged 22-34 years at cancer diagnosis, are reported; two of them had attenuated FAP. Grossly, one FAP-associated tumour and one sporadic tumour were multicentric and the others were solitary. Histologically, the tumours were encapsulated and exhibited a combination of cribriform, follicular, trabecular, solid, and papillary patterns of growth, with morular areas. Immunohistochemically, the tumour cells showed cytoplasmic expression of thyroglobulin, neuron-specific enolase, epithelial membrane antigen, high- and low-molecular-weight cytokeratins, vimentin, and bcl-2 protein; nuclear expression of oestrogen and progesterone receptors, and retinoblastoma protein; and cytoplasmic and nuclear accumulation of beta-catenin. Germline mutations of the adenomatous polyposis coli (APC) gene were investigated using the protein truncation test in four subjects, including two FAP individuals. Germline APC mutation was identified in only one FAP patient with the multicentric C-MV of PTC, who had a thymidine deletion at codon 512, resulting in a frameshift leading to a premature stop codon. No loss of heterozygosity of loci close to the APC gene was detected in tumour tissues from these four patients. Somatic mutation analysis of exon 3 of the beta-catenin gene (CTNNB1) revealed alterations in seven tumours from all five individuals: one at a serine residue (codon 29), three at amino acids adjacent to serine or threonine residues (codons 22, 39, and 44), and three at other amino acids (codons 49, 54, and 56). Moreover, each of two different tumours examined from two patients with the multicentric C-MV of PTC, had different somatic mutations of the CTNNB1 gene. Taken together, these data suggest that accumulation of mutant beta-catenin contributes to the development of the C-MV of PTC.

Adenocarcinoma, Papillary↗

PubMed2004

Neuronal nicotinic receptors: from structure to pathology.

Neuronal nicotinic receptors (NAChRs) form a heterogeneous family of ion channels that are differently expressed in many regions of the central nervous system (CNS) and peripheral nervous system. These different receptor subtypes, which have characteristic pharmacological and biophysical properties, have a pentameric structure consisting of the homomeric or heteromeric combination of 12 different subunits (alpha2-alpha10, beta2-beta4). By responding to the endogenous neurotransmitter acetylcholine, NAChRs contribute to a wide range of brain activities and influence a number of physiological functions. Furthermore, it is becoming evident that the perturbation of cholinergic nicotinic neurotransmission can lead to various diseases involving nAChR dysfunction during development, adulthood and ageing. In recent years, it has been discovered that NAChRs are present in a number of non-neuronal cells where they play a significant functional role and are the pathogenetic targets in several diseases. NAChRs are also the target of natural ligands and toxins including nicotine (Nic), the most widespread drug of abuse. This review will attempt to survey the major achievements reached in the study of the structure and function of NAChRs by examining their regional and cellular localisation and the molecular basis of their functional diversity mainly in pharmacological and biochemical terms. The recent availability of mice with the genetic ablation of single or double nicotinic subunits or point mutations have shed light on the role of nAChRs in major physiological functions, and we will here discuss recent data relating to their behavioural phenotypes. Finally, the role of NAChRs in disease will be considered in some details.

Aging↗

PubMed2005

Subtype C1 persistent infection of HHV-8 in a PEL patient.

PEL, a rare type of lymphoma constituting less than 5% of NHLs, has been recently identified as a distinct clinical and pathological entity among the B-cell lymphomas, with characteristic morphologic, immunophenotypic, molecular and viral features. ICC, PCR, RT-PCR and sequencing were carried out in biologicals samples from a 44-year-old, non-smoker Caucasian male patient of Greek nationality, HIV-1 negative and HCV positive. The ICC results showed CD30 + , Vimentin + , EMA + , Ki67 + , Pankeratin- and negative to B and T antibodies. In addition, HHV-8 was detected in pleural fluid. Examination of blood samples of the patient over a period of nearly two years showed a persistent infection of HHV-8. Phylogenetic analysis revealed a close relation to the C1 variant of HHV-8. The samples was also found EBV negative by PCR. Using a combination of clinical, morphological, immunohistochemical features and molecular biology techniques in this study we document a PEL case with persistent HHV-8 of genotype C1 infection.

Adult↗

PubMed2003

The effect of bilaterality, pathological features and surgical outcome in nonhereditary renal cell carcinoma.

PURPOSE: We evaluated the differences in cancer specific, distant metastasis-free and local recurrence-free survival in patients with sporadic subtype concordant bilateral synchronous renal cell carcinoma and those with unilateral renal cell carcinoma, controlling for the covariates of subtype, stage, tumor size, grade and necrosis. We also analyzed early surgical complications and long-term renal function in patients who underwent staged surgery and those who underwent a single operation for bilateral synchronous renal cell carcinoma. MATERIALS AND METHODS: We retrospectively evaluated 44 patients with sporadic subtype concordant bilateral synchronous renal cell carcinoma treated at our institution between 1970 and 1998. There were 32 patients with bilateral synchronous clear cell renal cell carcinoma and 12 with bilateral synchronous papillary renal cell carcinoma. These patients were compared with 1,714 with sporadic unilateral clear cell renal cell carcinoma and 322 with sporadic unilateral papillary renal cell carcinoma treated with partial or radical nephrectomy during that period. Outcomes were estimated using the Kaplan-Meier method and Cox proportional hazard models were used to test associations with outcome. RESULTS: Clinicopathological features were similar for patients with bilateral synchronous and unilateral renal cell carcinoma except for the incidence of multifocality, which was 28% and 33% for bilateral synchronous clear cell and papillary renal cell carcinoma compared with 2% and 7% for unilateral clear cell and papillary renal cell carcinoma, respectively. Cancer specific survival and distant metastasis-free survival in patients with bilateral synchronous disease was similar to that in those with unilateral disease when controlling for subtype, stage, tumor size, grade and tumor necrosis. However, patients with bilateral synchronous clear cell renal cell carcinoma were more likely to experience local recurrence even after controlling for these covariates. The majority of patients (84%) with bilateral synchronous disease underwent bilateral surgery at a single operation. The incidence of early surgical complications was low, in that only 2 patients had urinary extravasation, 3 had acute renal failure and 1 was ultimately rendered anephric and required hemodialysis. CONCLUSIONS: The incidence of multifocality was greater in patients with bilateral synchronous renal cell carcinoma than in those with unilateral renal cell carcinoma. There were no statistically significant differences in cancer specific and distant metastasis-free survival in patients with bilateral synchronous renal cell carcinoma and unilateral renal cell carcinoma of the same histological subtype. These results suggest that subtype concordant bilateral renal cell carcinoma is a result of multiple de novo primary events rather than primary renal cell carcinoma with contralateral renal metastasis. A surgical approach is appropriate for bilateral synchronous renal cell carcinoma and most cases can be approached at a single surgical procedure with acceptable morbidity.

Adult↗

PubMedDate not supplied

From the archives of the AFIP. Genitourinary rhabdomyosarcoma in children: radiologic-pathologic correlation.

Rhabdomyosarcoma is the most common tumor of the lower genitourinary tract in children in the first 2 decades of life. Most cases of genitourinary rhabdomyosarcoma are of the embryonal histologic subtype and include tumors of the bladder, prostate, testes and paratesticular sites, penis, perineum, vagina, and uterus. The natural history, pattern of metastatic spread, treatment, and prognosis of childhood rhabdomyosarcoma vary with the anatomic site of the lesion. In children with rhabdomyosarcoma of the bladder or prostate, presenting signs and symptoms include urinary or fecal retention, dysuria, urinary tract infection, and hematuria. Paratesticular rhabdomyosarcoma produces painless scrotal swelling, which may be ignored until the tumor has reached a large size. Vaginal tumors may manifest as a prolapsing mass in the introitus. Radiologic studies of children with genitourinary rhabdomyosarcoma reflect the nonspecific gross features of the tumor, which may be ill defined with infiltrative margins or well circumscribed by a pseudocapsule of compressed tissue. The botryoid variant of embryonal rhabdomyosarcoma results when submucosal tumor produces a polypoid mass resembling a cluster of grapes within a hollow structure. Botryoid morphology is characteristic, but not specific, for rhabdomyosarcoma within the vagina or urinary bladder, since yolk sac tumor and "tumoral" cystitis may have a similar appearance. Invasion of adjacent structures by the primary tumor may make the precise anatomic origin of genitourinary rhabdomyosarcoma difficult to determine on cross-sectional images. Recent refinements in multidisciplinary therapeutic regimens combining chemotherapy, radiation therapy, and surgery have dramatically improved outcome for children with genitourinary rhabdomyosarcoma. Diagnostic imaging plays an important role in monitoring response to therapy.

Adolescent↗

PubMed2004

What are the pancreatic target cells for gastrin and its CCKB receptor? Is this a couple for cancerous cells?

The objectives of this review are to summarize, analyse and discuss the roles played by the CCK receptor subtypes and their agonists on pancreatic enzyme secretion, pancreas growth and regeneration, define the receptors specific target cells and evaluate the role of gastrin in pancreatic pathologies including cancer. In rodents, it is clear that the CCKARs present on pancreatic acinar cells play a major role in enzyme secretion. In large mammals, CCK does not seem to be the final mediator of enzyme release. In rat, gastrin and its CCKBR seem responsible for foetal pancreas growth while after birth, CCK was shown to be the most potent trophic factor via occupation of its CCKAR. In pig and human, no one has yet established a direct link between CCK, gastrin and pancreas growth. In rodent's pancreas, the CCKAR were observed on acinar cells as well as on islet's alpha and beta cells; in six other species, the CCKAR were present only on alpha and beta cells with the CCKBR always present on delta cells. The CCKBRs were overexpressed in acute pancreatitis and in metaplastic pancreas following duct ligation. In pancreatic cancer cells, a gastrin autocrine loop involving the CCKBR was suggested. The presence of both CCKR-subtypes and gastrin was observed in many pancreatic tumors; however, their role in cancer growth remains controversial.

Animals↗

PubMed1999

Neuropeptide Y: emerging evidence for a functional role in seizure modulation.

The high concentration of the tyrosine-rich polypeptide, neuropeptide Y (NPY), and the increase in the number of its receptor subtypes that have been characterized in the brain, raise the question of a functional role for NPY in the CNS. In addition to its peripheral actions on cardiovascular regulation, much attention has, therefore, been devoted to the CNS effects of NPY because of its stimulatory properties on food intake, its role in anxiolysis and its putative involvement in memory retention. Emerging evidence points to an important role for NPY in the regulation of neuronal activity both under physiological conditions and during pathological hyperactivity such as that which occurs during seizures. This article reviews recent studies that have shown the changes induced by seizures in the level and distribution of NPY, its receptor subtypes and their respective mRNAs in rat forebrain. Biochemical and electrophysiological findings in experimental models and tissue from human epilepsy sufferers suggest that NPY-mediated neurotransmission is altered by seizures. The pharmacological evidence and functional studies in NPY knockout mice highlight a crucial role for endogenous NPY, acting on different NPY receptors, in the control of seizures.

Animals↗

PubMed1994

Human papilloma virus associated with solitary squamous papilloma complicated by bronchiectasis and bronchial stenosis.

A 28-year-old man presented with recurrent pneumonias for 6 years. Chest radiograph and computed tomography showed localized bronchiectasis of the anterior segment of the left upper lobe. Bronchoscopy showed bronchial stenosis without an endobronchial lesion. After 6 weeks of antibiotic treatment, the patient had a recurrent pneumonia and underwent left upper lobectomy that showed a solitary squamous papilloma. In situ hybridization studies of the papilloma were reactive for human papilloma virus subtypes 6/11.

Adult↗