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PubMed2006

Epidemiology of childhood Hodgkins disease: is it different in developing countries?

Childhood Hodgkins Disease (HD) is a lymphoma that displays characteristic epidemiological, clinical and pathological features according to various geographic areas, particularly according to the socio-economic level of a given country. India presents a similar sex, age and subtype distribution as other emerging countries: high male-to-female ratio, younger age at presentation, high proportion of advanced stages and presence of constitutional symptoms, predominance of mixed cellularity type of HD. The etiology of HD is still the subject of controversy and investigation, but it may occur as a sequel of a viral infection during early childhood, such as Epstein-Barr virus (EBV). Most cases of Indian childhood HD are associated to EBV, while genetic predisposition is seen in very rare cases.

Adolescent↗

PubMed1990

Thyroid and parathyroid cancer.

The epidemiology, etiology, pathology, and management of thyroid and parathyroid carcinoma are discussed. Emphasis is placed on the clinical differences in the management and treatment of the various histologic subtypes of thyroid cancer. The biologic and prognostic differences among the various histologic types of thyroid cancer and their relationship to age are stressed.

Aged↗

PubMed1987

Thyroid and parathyroid cancer.

Aged↗

PubMed1996

[Abnormal T cell maturation in myasthenia gravis associated thymomas].

AIMS AND METHODS: Paraneoplastic myasthenia gravis is a thymoma-associated autoimmune disease, characterized by autoantibodies against the acetylcholine receptor (AChR). CD4+ AChR-specific T cells play a pivotal role in the production of autoantibodies. However, it is not known how the tumor is involved in the pathogenesis of autoimmunity. To address this question thymocyte maturation was followed in medullary, mixed and cortical thymomas using three-color FACS analysis. RESULTS: Compared to normal thymuses medullary thymomas were almost devoid of immature T cells and most intratumorous lymphocytes appeared to be of peripheral origin. In mixed and cortical thymomas maturation of thymocytes took place from the most immature precursors to thymomcytes with a mature phenotype. Only in the latter tumor subtypes immature CD4+/CD8-/CD3-thymocytes were significantly increased. In addition, a reduced production of mature CD4+ T cells suggests ineffective positive selection. Activated T cells were present in one medullary but none of the mixed or cortical thymomas. CONCLUSION: Each histological thymoma subtype is associated with a characteristic defect of T cell maturation. The contribution of medullary thymomas to the pathogenesis of myasthenia gravis (MG) might be a pathological intratumorous T cell activation. By contrast, an abnormal antigen-specific T cell selection may be the contribution of cortical and mixed thymomas to anti-AChR autoimmunity.

Antigens, CD↗

PubMed1997

Neuronal subtype-specific expression directed by the GABA(A) receptor delta subunit gene promoter/upstream region in transgenic mice and in cultured cells.

The promoter of the GABA(A) receptor delta subunit gene was analyzed in transgenic mice and in cultured cells to study sequences involved in neuronal subtype-specific gene expression. A 6.4-kb genomic fragment faithfully directed neuron-specific transcription of a lacZ reporter gene in the central nervous system. The transgene expression pattern in the cerebral cortex, hippocampal formation, thalamus, and brainstem was consistent with the regional and neuronal subtype-specific expression of the endogenous delta subunit protein in both developing and mature brain. In the cerebellum, however, the transgene was ectopically expressed in Purkinje cells and silent in granule cells, where the endogenous delta subunit is abundantly expressed. These mice provide a useful tool for investigating activity-dependent regulation of GABA(A) receptor expression under physiological and pathological conditions. Transfection studies using primary cortical neurons and astroglial cells revealed that the delta subunit gene promoter was selectively active in neurons even when truncated to a 267-bp core fragment. In conclusion, the delta subunit gene promoter/upstream region contains the information for neuronal subtype-specific expression in the entire brain except in the cerebellum and is selectively active in primary cortical neurons in vitro.

Aging↗

PubMed2004

CD87 (urokinase-type plasminogen activator receptor), function and pathology in hematological disorders: a review.

The analysis of CD87 (urokinase-type plasminogen activator receptor - uPAR) expression has a potential role in the diagnostic or prognostic work-up of several hematological malignancies, particularly acute leukemia and multiple myeloma. The distribution of CD87 in acute myeloid leukemia (AML) varies according to the FAB subtype (highest expression in M5 and lowest in M0). Functionally, it is conceivable that the expression of CD87 could contribute to the invasive properties of the leukemic cells towards the skin and mucosal tissues as reflected by the clinical behavior of CD87 high cases. The lack of or weaker expression of CD87 on blast cells from ALL patients supports the concept that CD87 investigation might help in the distinction of AMLs from lymphoid malignancies. Among lymphoproliferative disorders, the expression of CD87 is exclusively found in pathological plasma cells. Since plasma cells also coexpress some adhesion molecules such as CD138 and CD56, this observation is consistent with the capacity of these cells to home in the bone compartment. High levels of soluble uPAR appear to represent an independent factor predicting worse prognosis and extramedullary involvement in multiple myeloma.

Hematologic Diseases↗

PubMed2000

Soft tissue aspiration cytopathology.

BACKGROUND: Fine-needle aspiration (FNA) biopsy as a diagnostic modality for the pathologic evaluation of soft tissue neoplasms and non-neoplastic soft tissue mass lesions is uncommon and controversial. This procedure contrasts with more traditional diagnostic methods such as marginal excision, incisional (open) biopsy, or even core biopsy to procure tissue from somatic sites. METHODS: The authors reviewed the results of cytopathologic diagnoses obtained by fine-needle aspiration biopsy over a consecutive 11-month period in patients that presented primarily with a palpable soft tissue mass. A few patients with deep non-palpable soft tissue masses also were evaluated by radiologically guided FNA. Cytopathologic diagnoses were verified by different means including tissue examination either by concurrent cell block or subsequent surgical biopsy, flow cytometry, clinical outcome, or repetition of the FNA procedure. Patients were followed for a minimum of one year to evaluate the mass clinically, to determine whether any further therapy was administered, and to assess disease status. RESULTS: Eighty-two aspirates were performed without complications from 77 patients ranging from 12-88 years of age (mean = 50 yrs.) with men outnumbering women 1.5:1. Soft tissue masses were most common in the extremities (41 cases), followed by the trunk (34 cases), retroperitoneum (5 cases), and head and neck (2 cases). Fine-needle aspirates were diagnosed as malignant in 42 (51%), benign in 32 (39%), nondiagnostic in 6 (7%), and atypical in 2 (2%) cases. Malignant aspirates were comprised of 24 sarcomas (57%), 9 carcinomas (21%), 6 malignant lymphomas (14%), and 3 melanomas (7%). Twenty-two aspirates (52%) had an initial diagnosis of malignancy, whereas 18 (43%) represented metastatic and 2 (5%) recurrent neoplasms. Confirmation of the cytopathologic diagnosis was by concurrent or subsequent tissue examination in 57%, flow cytometry in 5%, clinical outcome in 34%, and repeat aspiration in 4%. One false negative and no false positive diagnoses were issued for a sensitivity and specificity of 100% and 97% respectively in distinguishing benign and malignant lesions by FNA. Of the malignant aspirates, 83% could be subtyped whereas 72% of benign aspirates were correctly subtyped. For primary soft tissue sarcomas, 12 of 19 (63%) were accurately subtyped. In 48% of cases a concurrent cell block was obtained and found diagnostically useful in 54% of them. CONCLUSIONS: Aspiration cytopathology of soft tissue mass lesions using FNA biopsy can be an accurate and minimally invasive method for the initial pathologic diagnosis of primary benign and malignant soft tissue masses, for the pathologic confirmation of metastatic tumors to soft tissue, and for the documentation of locally recurrent soft tissue neoplasms. FNA cytopathology is capable of specifically subtyping a large percentage of primary and metastatic soft tissue tumors if cellular material either in the form of a cell block or flow cytometry is obtained in addition to cell smears.

Adolescent↗

PubMed1999

Concurrent and predictive validity of antisocial personality disorder subtyping among substance abusers.

Three hundred seventy inpatient and outpatient substance abusers were divided according to presence and subtype of antisocial personality disorder (APD) into groups comparing: a) adult antisocial behavior (AAB) versus full APD; b) APD with low versus high sociopathy; c) APD with versus without lifetime depression; and d) APD with versus without other axis II disorders. Multivariate regression was used to predict the unique contribution to the variance in baseline and 12-month follow-up measures of substance use, psychiatric severity, and personality. The presence of comorbid axis II pathology was the strongest predictor of baseline severity in all three domains. APD substance abusers with lifetime depression exhibited greater baseline to follow-up reductions in psychiatric severity than those APD substance abusers without a history of depression. All APD subtypes improved over time with treatment, suggesting that this diagnosis does not necessarily indicate poor prognosis.

Adult↗

PubMed1992

Role of central GABAB receptors in physiology and pathology.

There are two major classes of gamma-aminobutyric acid (GABA)-sensitive receptors: GABAA and GABAB. The GABAA receptor, the better known of the two GABA receptors, is a heterooligomeric complex that forms a chloride channel. Multiple subtypes of the GABAA receptor result from the composition of different subunits. In contrast to the GABAA receptor, the GABAB receptor protein has not been isolated and purified to homogeneity. Various effector systems, however, have been identified for the GABAB receptor using a limited GABAB-specific pharmacologic reportoire. In almost all cases, activated GABAB receptors employ a guanosine triphosphate-binding protein to transduce a signal intracellularly. There may be multiple subtypes of the GABAB receptor. Because the responses elicited by activation of GABAB receptors are small in terms of their intensity and are considered to be modulatory, the role these receptors play in the central nervous system (CNS) may not be very obvious. However, it is our view that in a finely tuned instrument such as the brain, treatment with neuromodulators (drugs that produce slight changes in brain neurochemistry) may be safer than most current drugs. Moreover, neuromodulators may have far greater potential as pharmacotherapeutic agents for CNS disorders. Thus, in this article, we will review the pharmacologic characteristics of the GABAB receptor, known physiologic roles that this receptor plays in the CNS, and the importance of this receptor in certain disease states.

Animals↗

PubMed1999

[Vascular remodeling and angiotensin II].

Numerous pharmacological approaches have failed to modify the high incidence of restenosis after balloon coronary angioplasty. This inability to alter the restenosis process was caused in part by our incomplete understanding of its pathology. Neointimal formation and geometric remodeling cause the restenosis after angioplasty. The development of restenosis involves vascular smooth muscle cells (VSMCs) migration and proliferation. Angiotensin II has been shown to stimulate the growth of VSMCs via an action on the angiotensin II AT1 receptor subtype. Angiotensin II AT1 receptor antagonists can block the angiotensin II-induced these actions. Angiotensin II AT1 receptor antagonists may block the restenosis after balloon coronary angioplasty.

Angioplasty, Balloon, Coronary↗

PubMed1991

Early alterations of Gi/Go protein-dependent transductional processes in the retina of diabetic animals.

The early alterations of G-protein-dependent transductional mechanisms have been characterized in the retina of alloxan-treated diabetic rats. Five weeks after alloxan injection, pertussis toxin radiolabeling of Gi/Go proteins was markedly reduced in the retina of diabetic animals, suggesting either a reduced expression and/or the presence of some structural modification of these G-protein subtypes. The functional activity of Gs proteins, measured as stimulation of membrane adenylate cyclase by dopamine, did not seem to be impaired at this stage of the pathology; basal adenylate cyclase activity was indeed increased in diabetic rats, consistent with the observed reduction of Gi/Go inhibitory proteins. Such functional alterations of the cAMP producing system were causally related to diabetes induction, since they were reversed by treatment of diabetic animals with insulin. These results suggest that G-protein dependent transduction mechanisms are altered in the retina of diabetic animals, and that a defect of Gi/Go proteins could represent an early transductional damage in the development of diabetic retinopathy.

Adenylyl Cyclases↗

PubMed2001

Rectal localization of metastatic lobular breast cancer: report of a case.

The incidence of extrahepatic gastrointestinal metastases from breast cancer is reported in the literature only as necroscopy studies (6-18 percent); they usually originate from lobular or a mixed ductal-lobular subtype. Nonspecific presenting symptoms, death of the patients caused by other more frequent metastases, and variable radiographic features mimicking primary neoplasms cause a clinical underestimation of this pathology. We report here a case of rectal metastasis from a lobular carcinoma eight years after mastectomy.

Biopsy↗

PubMed2005

First trimester diagnosis of partial mole.

BACKGROUND: Partial mole is one of the two distinctive subtypes of hydatidiform mole. It is usually paternally derived triploid conceptions in which embryonal development occurs in association with trophoblastic hyperplasia. The definite diagnosis is confirmed by pathological and cytogenetic studies. Ultrasound might be helpful to diagnose partial mole in the first trimester. CASE: A 25-year-old woman, gravida 2, para 0-0-1-0, was initially seen for antenatal care at 6 weeks' pregnant. Ultrasound was undertaken at 13 weeks' pregnancy due to her first fetal anomaly, which demonstrated partial mole and embryonic death. The serum beta hCG was 190,900 mIU/ml. Suction curettage was performed without complication. Histopathological study confirmed partial mole and cytogenetic study of the placenta revealed an uncommon karyotype, mosaicism of triploid (69,XXX/69,XXY). Serum beta hCG was declined and negative at 8 weeks. The patient was well and serum beta hCG remained normal throughout 6 months of follow-up. CONCLUSION: Although the majority of partial mole pregnancies cannot be detected by routine first trimester ultrasound examination, first trimester ultrasound can be helpful in some cases, such as this one. If partial mole is sonographically suspected, it should be confirmed with histopathology and cytogenetic studies. The management is similar to complete mole including prompt evacuation and careful monitoring of beta hCG.

Adult↗

PubMed2005

Diabetes and cognitive impairment. Clinical diagnosis and brain imaging in patients attending a memory clinic.

BACKGROUND: Diabetes is a risk factor for dementia,but the issue whether this concerns only vascular dementia or also Alzheimer's disease is debated. We compared the clinical diagnoses and abnormalities on brain MRI in patients with or without diabetes who received standardised, detailed diagnostic studies at a memory clinic, in order to establish whether one specific type of dementia or specific MRI abnormalities were more common in diabetes. PATIENTS AND METHODS: Patients who visited our memory clinic between January 2002 and June 2004 were divided into a group with (n = 42) or without diabetes (n = 389). The diagnoses were recorded, and MRI scans were rated for (sub)cortical atrophy, medial temporal lobe atrophy, infarctions, and white matter changes. RESULTS: The proportion of Alzheimer's disease (36% versus 28%; OR 1.1 (95% CI 0.5-2.2), adjusted for age and sex), vascular dementia (5% versus 2%; OR 2.4 (0.5-12.1)), and so called "cognitive impairment no dementia" (24% versus 17%; 1.3 (0.6-2.9)) was similar in patients with or without diabetes. On MRI lacunar and cortical infarctions were more common and cortical atrophy more pronounced among diabetic patients. By contrast, the severity of white matter changes was similar in the two groups. CONCLUSION: The relative frequency of different diagnoses among diabetic and non-diabetic patients attending a memory clinic was similar, indicating that diabetes does not predispose to one particular subtype of dementia. The imaging findings support the notion that the increased risk of cognitive decline and dementia in elderly subjects with diabetes is due to dual pathology, involving both cerebrovascular disease and cortical atrophy.

Aged↗

PubMed2005

Anal localization as first manifestation of metastatic ductal breast carcinoma.

The incidence of extrahepatic gastrointestinal metastases from breast cancer is reported in the literature only as necroscopy studies (6-18%); they usually originate from lobular or a mixed ductal-lobular subtype. Nonspecific presenting symptoms, death of the patients caused by other more frequent metastases, and variable radiographic features mimicking primary neoplasms cause a clinical underestimation of this pathology. We report here a case of rectal metastasis from an invasive ductal carcinoma (IDC). This is to our knowledge, the first recorded instance of an anal metastasis from IDC.

Aged↗

PubMed1994

The mouse 5-hydroxytryptamine1B receptor is localized predominantly on axon terminals.

The 5-hydroxytryptamine1B receptor is a serotonin receptor subtype which is expressed predominantly in the basal ganglia. It has been suggested to play a role in movement and appetite control as well as in certain pathological states such as migraine. The recent cloning of the 5-hydroxytryptamine1B gene as well as the discovery of a radioligand that labels in rodents 5-hydroxytryptamine1B and possibly 5-hydroxytryptamine1D alpha receptors (S-CM-G[125I]TNH2) allowed us to compare the distribution of the messenger RNA and of the protein in mouse brain sections. A high 5-hydroxytryptamine1B messenger RNA level is found in the caudate-putamen in medium spiny neurons that project to the globus pallidus and the substantia nigra. In contrast, no messenger RNA is expressed in the globus pallidus and substantia nigra although these structures reveal the highest level of 5-hydroxytryptamine1B binding sites. In the hippocampus, 5-hydroxytryptamine1B messenger RNA is localized in the cell bodies of pyramidal cells of the CA1 field while the protein is found predominantly in the dorsal subiculum, a projection zone for the CA1 pyramidal neurons. In the cerebellum, 5-hydroxytryptamine1B messenger RNA is expressed in the Purkinje cells, which display no receptor binding sites. Conversely, moderate binding is found in the deep nuclei of the cerebellum, the main projection zone of the Purkinje cells. 5-Hydroxytryptamine1B sites are also detected in the superficial gray layer of the superior colliculus and the lateral geniculate nucleus, brain regions containing the terminals of retinal ganglion cells. The soma of these ganglion cells express high levels of 5-hydroxytryptamine1B messenger RNA while no 5-hydroxytryptamine1B binding sites were found in the retina. This study demonstrates that the main brain regions, expressing 5-hydroxytrypamine1B messenger RNA contain low densities of 5-hydroxytryptamine1B binding sites. Conversely, the major projection areas of these anatomical structures do not express detectable levels of 5-hydroxytryptamine1B messenger RNA, but present a high density of binding sites. In addition, our data suggest that the distribution of the 5-hydroxytryptamine1D alpha binding sites is different from that of the 5-hydroxytryptamine1D alpha messenger RNA. These results together with previous lesion studies, indicate that the 5-hydroxytryptamine1B and possibly the 5-hydroxytryptamine1D alpha receptors are localized predominantly on axon terminals, while their expression is low or absent at the somatodendritic level. The 5-hydroxytryptamine1D alpha proteins might therefore contain an addressing signal allowing their transport toward nerve endings.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed2003

Histamine and epidermal growth factor in women with fibrocystic changes of the breast.

In this study, the blood serum concentrations of histamine (HA) and epidermal growth factor (EGF) of women with fibrocystic changes (FCCs) of the breast were estimated. The control group comprised 32 women (mean age 44.9+/-4.4 years) without any pathologic changes in their breasts. The study group was made up of 81 women (mean age 44.5+/-3.5 years) with FCCs. The changes were divided into three subtypes: fibrous, cystic, and fibrocystic. In women with FCCs the concentrations of HA (P<0.01) and EGF (P<0.01) were significantly higher than in women without any changes in their breasts (control group). The concentration of EGF in blood serum was significantly higher in women with the fibrocystic subtype of FCC (P<0.001) than in healthy women. No correlations between the blood serum concentrations of HA and of EGF were found in either the control group or the study group. The significantly higher blood serum concentrations of HA and EGF women with FCCs than in healthy women suggest that HA and EGF have a role in the development of this disease.

Adult↗

PubMed2000

Functional coupling of G proteins to endothelin receptors is ligand and receptor subtype specific.

1. The aims of the present study were (a) to determine the identity of the G proteins with which the endothelin receptor interacts and whether this interaction is subtype specific and (b) to determine whether agonist exposure can result in specific coupling between the endothelin receptor and G proteins. 2. Coupling between endothelin A (ET(A)) or endothelin B (ET(B)) receptors and G proteins was assessed in two fibroblast cell lines, each expressing one receptor subtype. Four ligands, ET-1, ET-3, SRTXb, and SRTXc, were used for receptor stimulation. The G protein alpha-subunit coupled to the receptor was identified by immunoprecipitation with an antibody against the endothelin receptor and immunoblotting with specific antibodies against different G protein alpha-subunits. 3. Unstimulated ET(A) and ET(B) receptors (ET(A)R and ET(B)R, respectively) were barely coupled to Go(alpha). The unstimulated ET(A)R coimmunoprecipitated with Gi3alpha, whereas the unstimulated ETBR was much less strongly coupled to Gi3alpha. The coupling of ETBR to Gi1Gi2 alpha-subunits was much stronger than the coupling of ET(A)R to these alpha-subunits. Stimulation with the different ET agonists also resulted in differential coupling of G proteins to the receptor subtypes. All four ligands caused a strong increase in coupling of the ET(B)R to Gi3alpha, whereas coupling of the ET(A)R to this subunit was not affected by ET-1 and was even decreased by SRTXc. On the other hand, all four ligands caused a much greater increase in the coupling of ET(A)R to G(q)alpha/G11alpha than in the coupling of ET(B)R to these alpha-subunits. Ligand-induced coupling between the receptors and the Gi1 and Gi2 alpha-subunits is similar for the two receptor subtypes. The same was true for ligand-induced coupling of the receptors to Go(alpha), except that ET-3 increased the coupling of this alpha-subunit to ET(B)R and decreased the coupling to ET(A)R. Taken together, the results of this study show that coupling between ET receptors and G proteins is ligand and receptor subtype specific. 4. It remains to be established whether this diversity of receptor-G protein coupling is of relevance for the various endothelin signaling pathways and/or pathological states.

Animals↗