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PubMed2000

Malignant mesothelioma in subjects with Marfan's syndrome and Ehlers-Danlos syndrome: only an apparent association?

Malignant mesothelioma is a rare neoplasm which could be favored by an hereditary predisposing factor. So far, malignant mesothelioma have never been described in patients with hereditary diseases of the connective tissue. Here, we report some cases of mesothelioma affecting subjects who were not exposed to inhalation of asbestos. One of these subjects was affected by Ehlers-Danlos syndrome, whereas in two brothers, mesothelioma was associated with Marfan's syndrome. The observation of the same histologic subtype of mesothelioma in two brothers and the coexistence of two pathologic conditions of mesodermal origin indicate the presence of hereditary factors predisposing to the cancerogenic action of even small amounts of asbestos. Structural alterations of collagen and primary immunodeficiency may represent the host factor inducing development of the neoplasm. We conclude that the association between these rare disorders of the connective tissue and mesothelioma may not be coincidental, but could be the result of the exposition to small amounts of asbestos in predisposed individuals.

Adult↗

PubMed1986

Differentiation of calcium entry blockers into calcium channel blockers and calcium overload blockers.

The heterogeneity of the several subgroups of calcium-antagonistic drugs requires a rigid and well-defined differentiation of this type of agents. From the chemical point of view verapamil-like drugs, dihydropyridines, benzothiazepines and diphenylalkylamines should be distinguished. Among these largely different groups no obvious relationship between chemical structure and calcium-antagonistic activity can be recognized. Irrespective of the chemical classification all above-mentioned compounds inhibit the entry of calcium into cells. However, from a pharmacological point of view a distinction should be made between calcium channel blockers and calcium overload blockers. Calcium channel blockers selectively and competitively inhibit the transmembranous slow inward current, which is carried by calcium ions both in cardiac tissues and in vascular smooth muscle under physiological conditions. However, calcium overload blockers only inhibit the overload of the cell with calcium ions, which occurs under pathological, ischemic conditions. Finally, a survey is given of the various subtypes of calcium-antagonistic drugs with respect to their organ specificity and therapeutic applicability.

Animals↗

PubMedDate not supplied

Cytopathologic and clinicopathologic features of ovarian hepatoid carcinoma. A case report.

BACKGROUND: Hepatoid carcinoma is a rare ovarian tumor and is thought to be a different histopathologic subtype from hepatoid-type yolk sac tumor based upon its pathologic features. However, the cytopathologic characteristics of ovarian hepatoid carcinoma (OHC) have not been reported previously. We report the clinicopathologic and cytopathologic features and immunoreactivity of a case of OHC. CASE: A 36-year-old woman presented to our department with lower abdominal pain. A left ovarian tumor was found on pelvic examination, magnetic resonance imaging and computed tomography. The tumor was diagnosed as a hepatoid carcinoma of the left ovary based upon the histopathology of the surgically resected specimen. Cytopathologic specimens from a tumor touch preparation of the tumor exhibited pleomorphic tumor cells with abundant cytoplasm. The nuclei contained rough, granular chromatin and large, prominent nucleoli. Several tumor cells were multinucleated. Tumor cells were immunoreactive for alpha-fetoprotein (AFP). Hematoxylin and eosin staining revealed that the tumor cells were in a sinusoidal pattern resembling hepatocellular carcinoma without any glandular formation. The tumor cells were negative for human chorionic gonadotropin while positive for AFP, alpha-1-antitripsin, CA-125 and carcinoembryonic antigen. CONCLUSION: Cytopathologic examination is of considerable aid in the diagnosis of OHC since cytopathologic preparations highlight the characteristic cell pleomorphism.

Adult↗

PubMed2005

Practicalities of genetic studies in human stroke.

Considerable evidence suggests genetic factors are important in the pathogenesis of multifactorial stroke. However, studies identifying the underlying genes have been largely disappointing. This chapter reviews the different approaches and their relative merits. It is likely stroke is a polygenic disorder and that underlying genes may interact within environmental risk factors. Stroke itself is a syndrome caused by a number of different pathologies, which may result from different genetic predispositions. Therefore accurate stroke subtyping is likely to be important in identifying genetic associations. Previous studies have suffered from small sample size, lack of adequate phenotyping, and poor case-control matching. The most popular approach to identifying genes in human polygenic ischemic stroke has been the candidate gene approach. The relative merits of this approach are discussed. More recently this has been extended to family-based association studies. Linkage-based approaches have been used less although current studies are implementing the affected-sibling-pair method. In the future genome-wide association studies are likely to become more widely used.

Case-Control Studies↗

PubMed2001

Therapy of bronchial asthma with adenosine receptor agonists or antagonists.

Adenosine is an endogenous nucleoside that is released under pathological conditions and interacts with four G-protein-coupled receptor subtypes. These receptors are widely distributed throughout the body. They are involved in many central and peripheral processes, including immunological and inflammatory responses. In inflammatory and asthmatic conditions, the extracellular concentration of adenosine increases in the airway tissue. It enhances mast cell degranulation and bronchoconstriction, but may also inhibit eosinophil or lymphocyte function or modulate reactive oxygen species generation in neutrophils. Despite a large number of studies clearly indicating the effects of adenosine in vitro, many aspects of the mechanisms involved in the adenosine-mediated responses are still unclear, and our knowledge is limited in understanding the complex multifactorial interactions occurring in the whole body. The discovery of adenosine receptor compounds acting with increasing selectivity will bring new approaches to the use of adenosine receptor agonists and antagonists and may clarify some of the current uncertainties. On the basis of our present knowledge, the development of adenosine A(2A)- or (A3)-receptor agonists as antiinflammatory agents or A(2B)-receptor antagonists as inhibitors of mast cell degranulation for the treatment of asthma holds promise.

Journal Article↗

PubMed2005

[Analysis of prognostic factors in 159 cases of cervical adenocarcinoma].

OBJECTIVE: To assess prognostic factors in patients with cervical adenocarcinoma. METHODS: Totally 159 cases of primary cervical adenocarcinoma were diagnosed in Cancer Hospital, Peking Union Medical College between 1992 and 2002. Clinical and pathological data including patients'age, delivery, tumor size, stage, grade, histological subtype, Pap smear, serum CA125 and treatment were reviewed. Mean age at presentation was 51.4 years. And the mean follow-up time was 59.8 months. According to the International Federation of Gynecology and Obstetrics (FIGO), patients with stages I-IV accounted for 13.2%, 34.0%, 45.3% and 7.5%, respectively. Survival analysis was carried out using SPSS software version 11.0. RESULTS: The overall 5-year survival rate was 47.9%. It was 86.1%, 56.4%, 36.0% and 0 for stages I, II, III and IV respectively. And 29.6% cases experienced recurrence or distant metastasis. The 5-year survival rate for them was 17.3%. In univariate analysis, tumor size (P = 0.009), stage (P < 0.01) and elevated serum CA125 values (P = 0.039) were significant factors for survival. In the group of 27 cases who received surgery, the survival was significantly poorer for cases with pelvic lymph node metastases (P = 0.001) and deep stromal invasion (P = 0.009). Only stage and pelvic lymph node metastases remained significant predictors for survival when multivariate analysis was performed. CONCLUSIONS: This retrospective study suggests that FIGO stage and pelvic lymph node metastasis are independent factors in prediction of survival in cervical adenocarcinoma. Survival rate remains to be improved.

Adenocarcinoma↗

PubMed2006

[A case of transmesocolic hernia in elderly person without a history of operation].

Internal hernia is defined as the herniation of viscera through an anatomic or pathologic opening within the boundaries of peritoneal cavity. Transmesocolic hernia, a subtype of internal hernia, has a herniated sac through the transverse mesocolon. Transmesocolic hernia has been rarely described in the literature, and most of reported cases were associated with a history of operation or congenital anormaly. A 72-year-old female with chronic intermittent abdominal pain and bloating was admitted. Small bowel series showed multiple jejunal loops confined to the left upper quadrant of abdomen. Abdomen spiral computed tomography (CT) showed a cluster of mildly dilated small bowel loops with mesenteries on the same area. On the three-dimensional reconstruction CT scan, a herniated sac through the transverse mesocolon was identified. She was diagnosed as transmesocolic hernia by using the three-dimensional reconstruction CT and small bowel series, without surgical exploration. The symptoms were managed with conservative measures.

Aged↗

PubMed1995

Histopathology of childhood renal tumors.

The different subtypes of childhood renal tumors are well defined both clinically and pathologically. Classification and estimation of prognosis are feasible even after chemotherapy. A small group of tumors remains in which an estimate of prognosis is difficult. This is especially true for Wilms tumors with persistent blastema after chemotherapy. It is to be hoped that studies of the molecular genetics of these tumors will yield new data that will help refine therapeutic strategies.

Anaplasia↗

PubMed1997

Influence of hepatitis C virus genotypes and HIV infection on histological severity of chronic hepatitis C. The Hepatitis/HIV Spanish Study Group.

OBJECTIVES: The factors influencing the histological severity of chronic hepatitis C (CHC) have not been well established. We therefore investigated the effect of hepatitis C virus (HCV) genotypes and human immunodeficiency virus (HIV) infection on histological liver damage in a cohort of intravenous drug users with CHC. METHODS: We analyzed the histological activity score and the HCV genotypes in 59 HCV-RNA-positive patients with biopsy-proven CHC. Forty-eight (81%) of them had concomitant HIV infection with a CD4+ cell count above 200 x 10(6) cells/L and an absence of AIDS-defining conditions. Multivariate analysis was performed to determine the features associated with the histological severity. RESULTS: Minimal/mild hepatitis was found in 16 patients (27%), moderate chronic hepatitis in 29 (49%), and severe chronic hepatitis in 14 (24%). Patients with HCV subtype 1b had a higher histological score than others (8.7 +/- 3.3 vs. 6.5 +/- 3.2, p = 0.012), either as single or mixed infections. In multivariate analysis, HIV-infected individuals had a higher score of piecemeal necrosis (OR = 21.7, p = 0.002) and a higher stage of fibrosis (OR = 17.9, p = 0.004) than patients without HIV infection. HIV infection and HCV genotype 1b were found to be independent factors of histological severity. CONCLUSIONS: Liver damage in patients with CHC seems to be directly influenced by HCV subtypes. Infection by HCV subtype 1b is closely associated with more severe forms of liver pathology. Furthermore, the presence of HIV infection is an independent factor associated with more aggressive histological damage. In these patients, higher degrees of piecemeal necrosis and fibrosis are commonly seen.

Adult↗

PubMed2005

Inheritance of a novel COL8A2 mutation defines a distinct early-onset subtype of fuchs corneal dystrophy.

PURPOSE: To characterize the genetic basis and phenotype of inherited Fuchs corneal dystrophy (FCD). METHODS: DNA from blood was used for genome-wide linkage scans with tandem repeat polymorphisms. Mutation detection involved sequencing PCR-amplified exons. Families with FCD were clinically evaluated and graded on the Krachmer severity scale. Confocal specular microscopy visualized the morphology of endothelial guttae, small protrusions of Descemet's membrane that are characteristic of FCD. RESULTS: Linkage was obtained to 1p34.3-p32 for the autosomal dominant kindred originally reported by Magovern in 1979. All 21 cases with FCD and one with posterior polymorphous dystrophy were heterozygous for L450W, a novel point mutation in the COL8A2 gene. Of 62 independent cases of familial FCD, none had the previously reported mutations in COL8A2. Corneal guttae in COL8A2 patients were small, rounded, and associated with the endothelial cell center. This contrasts with common FCD, in which guttae were larger, sharply peaked, and initially positioned at edges of endothelial cells. The profile of age and disease severity for the L450W FCD kindred suggested that disease onset occurred in infancy, compared with an average age of onset of 50 years estimated for 201 familial FCD patients in 62 other families. CONCLUSIONS: A novel pathogenic L450W COL8A2 mutation was identified and its highly distinctive pathology characterized. This indicates that COL8A2 mutations give rise to a rare subtype of FCD. This study also provides the first direct evidence that COL8A2-FCD progresses from early to late stages in 25 years, a rate similar to that estimated for late-onset FCD.

Adolescent↗

PubMed1981

Dopamine receptors: subtypes, localization and regulation.

Receptor binding studies with a variety of dopaminergic ligands have confirmed behavioral and biochemical findings that the central nervous system and peripheral nervous system contain several dopamine receptor subtypes. These subtypes can be discriminated on the basis of their agonist-antagonist pharmacological specificities, linkage to adenylate cyclase, cellular location, regulation by guanine neucleotides and ions, and involvement in several human diseases. Although questions remain unanswered, progress is rapidly being made in equating the subgroupings arrived at by these different experimental approaches. Dopamine receptors are regulated by a number of factors. Acutely, guanine nucleotides and some ions regulate agonist but not antagonist binding and are essential for receptor coupling with adenylate cyclase. Chronically, changes in the level of dopaminergic stimulation modulate the number of at least some receptor subtypes, resulting in "up or down regulation." An increase in receptor number appears central to the pathology of Parkinson's disease, tardive dyskinesia, and perhaps schizophrenia. Animal models indicate that it may be possible to exploit inherent capabilities for receptor modulation in clinical therapy. The therapeutic precedents set by the indentification of distinct subtypes of adrenoreceptors. histamine, and cholinergic receptors portends and exciting future for dopamine receptor research.

Adenylyl Cyclases↗

PubMed1996

Microadenocarcinoma of the pancreas--morphologic pattern or pathologic entity? A reevaluation of the original series.

The term microadenocarcinoma was first proposed for a subtype of pancreatic carcinoma by Cubilla and Fitzgerald in 1975 based largely on the morphological features of 15 cases. Since that time, no independent studies have appeared in the English literature to address whether microadenocarcinoma represents a distinctive tumor or a pattern of growth, and some authors have questioned its existence as a definable entity. Immunohisto-chemistry is now available to allow the identification of lines of differentiation in pancreatic neoplasms, on which their classification is largely based. Reasoning that heterogeneity of differentiation between different cases would not justify the separation of microadenocarcinomas from other better defined pancreatic neoplasms, we reevaluated 12 cases from the original series using antibodies for acinar, endocrine, and ductal differ-entiation. Two distinctive morphological patterns were identified: microglandular and solid cribriform. The microglandular cases (n = 6) were not separable from typical ductal adenocarcinomas either morphologically or immunophenotypically. Of the solid-cribriform cases (n = 6), immunohistochemistry revealed three to be acinar cell carcinomas, one an endocrine carcinoma, one a mixed endocrine-ductal carcinoma, and one a ductal adenocarcinoma. We concluded that with the benefit of further study, most of these cases could be reclassified as other types of pancreatic carcinoma. Microadenocarcinoma is best regarded as a pattern of growth associated with an aggressive clinical course rather than a distinctive entity.

Adult↗

PubMed1981

Pathology of rhabdomyosarcoma: experience of the Intergroup Rhabdomyosarcoma Study, 1972-78.

A preliminary evaluation of histologic subtypes of rhabdomyosarcoma has shown that the alveolar pattern is associated with a significantly shorter survival when the patient has localized disease that has been completely excised at diagnosis. New histologic variants of undifferentiated sarcoma have been identified, but the clinical significance of these variants remains to be determined. Study of postmortem data of children placed on the Intergroup Rhabdomyosarcoma Study has shown several important clinical facts: Patients with head and neck parameningeal primary sites have a high incidence of treatment failures because the tumor extended into the adjacent central nervous system, with or without spinal fluid spread. Primary sites in the extremities and genitourinary tract are associated with an increased rate of regional lymph node spread. Systematic study of more patients is required before this association can be fully evaluated.

Antineoplastic Agents↗

PubMed1994

Factor analysis of symptom subtypes of obsessive compulsive disorder and their relation to personality and tic disorders.

Despite advances in our understanding of the pathology and genetics of obsessive compulsive disorder (OCD) and in our ability to successfully treat patients with medications and behavioral psychotherapy, the identification of homogeneous subgroups of patients with OCD has remained elusive. Once identified, such subgroups may be found related to treatment response, biological markers, or genetic transmission of OCD. To clarify identification of symptom subtypes, my colleagues and I administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) Symptom Checklist to 107 patients with OCD and applied principal components analysis (e.g., factor analysis) to these data. We then examined the correlations between these factor scores and the presence of comorbid tic and personality disorders, which are thought to be related to OCD. We found that three factors, which we named "symmetry/hoarding," "contamination/cleaning," and "pure obsessions," best explained the symptoms of the Y-BOCS Symptom Checklist. Only the first factor was significantly related to comorbid obsessive compulsive personality disorder or to a lifetime history of Tourette's syndrome or chronic tic disorder. Implications of these findings regarding possible clinical utility are discussed.

Adolescent↗

PubMedDate not supplied

Short rib-polydactyly syndrome type III: comparison of ultrasound, radiology, and pathology findings.

Short rib-polydactyly syndrome (SRPS; types I-IV) is an autosomal recessive, lethal skeletal dysplasia characterized by short-limb dysplasia, narrow thorax, and polydactyly. This syndrome is invariable and can be detected by 2-trimester ultrasound. The underlying gene has not been discovered yet. We report a case of SRPS subtype III Verma-Naumoff-Le Marec that was sonographically detected at 20 weeks' gestation and compare prenatal ultrasound with postmortem findings from pathology and radiology. Since the risk of recurrence is 25%, early ultrasound for consecutive pregnancies was advised and performed at 11+6 weeks' gestation in the following pregnancy without any findings. Ultrasound diagnosis in this rare case of SRPS is a valuable tool for identification and early management, since there are no specific biochemical or histopathological markers for this syndrome. Radiological and pathological findings confirmed SRPS type III and assisted in the differential diagnosis of the subtype.

Adult↗

PubMed2025

Tumor-immune partitioning and clustering algorithm for identifying tumor-immune cell spatial interaction signatures within the tumor microenvironment.

BACKGROUND: Growing evidence supports the importance of characterizing the organizational patterns of various cellular constituents in the tumor microenvironment in precision oncology. Most existing data on immune cell infiltrates in tumors, which are based on immune cell counts or nearest neighbor-type analyses, have failed to fully capture the cellular organization and heterogeneity. METHODS: We introduce a computational algorithm, termed Tumor-Immune Partitioning and Clustering (TIPC), that jointly measures immune cell partitioning between tumor epithelial and stromal areas and immune cell clustering versus dispersion. As proof-of-principle, we applied TIPC to a prospective cohort incident tumor biobank containing 931 colorectal carcinoma cases. TIPC identified tumor subtypes with unique spatial patterns between tumor cells and T lymphocytes linked to certain molecular pathologic and prognostic features. T lymphocyte identification and phenotyping were achieved using multiplexed (multispectral) immunofluorescence. In a separate hepatocellular carcinoma cohort, we replaced the stromal component with specific immune cell types-CXCR3+CD68+ or CD8+-to profile their spatial relationships with CXCL9+CD68+ cells. RESULTS: Six unsupervised TIPC subtypes based on T lymphocyte distribution patterns were identified, comprising two cold and four hot subtypes. Three of the four hot subtypes were associated with significantly longer colorectal cancer (CRC)-specific survival compared to a reference cold subtype. Our analysis showed that variations in T-cell densities among the TIPC subtypes did not strictly correlate with prognostic benefits, underscoring the prognostic significance of immune cell spatial patterns. Additionally, TIPC revealed two spatially distinct and cell density-specific subtypes among microsatellite instability-high colorectal cancers, indicating its potential to upgrade tumor subtyping. TIPC was also applied to additional immune cell types, eosinophils and neutrophils, identified using morphology and supervised machine learning; here two tumor subtypes with similarly low densities, namely 'cold, tumor-rich' and 'cold, stroma-rich', exhibited differential prognostic associations. Lastly, we validated our methods and results using The Cancer Genome Atlas colon and rectal adenocarcinoma data (n = 570). Moreover, applying TIPC to hepatocellular carcinoma cases (n = 27) highlighted critical cell interactions like CXCL9-CXCR3 and CXCL9-CD8. CONCLUSIONS: Unsupervised discoveries of microgeometric tissue organizational patterns and novel tumor subtypes using the TIPC algorithm can deepen our understanding of the tumor immune microenvironment and likely inform precision cancer immunotherapy.

Humans↗

PubMed2005

[The role of biomarkers CK7, Vim and P53 in the development of subtypes of endometrial carcinoma].

OBJECTIVE: Analyzing the protein expression of biomarkers CK7, Vim, and P53 to investigate their possible pathogenic roles in the development of variant subtypes of endometrial carcinoma. METHODS: Biomarkers CK7, Vim, and P53 were immunohistochemistry-stained among 131 endometrial carcinoma specimens including 93 endometroid, 8 adenoacanthoma, and 32 rare subtypes of adenosquamas carcinoma, clean cell carcinoma, and papillary carcinoma, which had been confirmed clinically and pathologically, and studied statistically with Fisher test and Cochran-Mantel-Haenszel (CMH) Test. RESULTS: Positive correlation was demonstrated among CK7, Vim, and P53 expression levels. The CK7 protein expression is increased, while the Vim and P53 are decreased in the subtype of endometrioid carcinoma. The clinical staging of endometriroid carcinoma is positively correlated with the expression of Vim. The positive rate of Vim and P53 is correlated with cytological differentiation of the carcinoma cells. CONCLUSION: Biomarkers CK7, Vim, and P53 are playing pathogenic roles, assuming as a mutual transcriptional modulator, and Vim but not P53 is likely the favorable prognostic factor, in the development of variant subtypes of endometrial carcinoma in addition to a evaluating the treatment.

Adult↗

PubMed1997

Meta-analysis of the Hachinski Ischemic Score in pathologically verified dementias.

Our objectives were to investigate the utility of the Hachinski Ischemic Score (HIS) in differentiating patients with pathologically verified Alzheimer's disease (AD), multi-infarct dementia (MID), and "mixed" (AD plus cerebrovascular disease) dementia, and to identify the specific items of the HIS that best discriminate those dementia subtypes. Investigators from six sites participated in a meta-analysis by contributing original clinical data, HIS, and pathologic diagnoses on 312 patients with dementia (AD, 191; MID, 80; and mixed, 41). Sensitivity and specificity of the HIS were calculated based on varied cutoffs using receiver-operator characteristic curves. Logistic regression analyses were performed to compare each pair of diagnostic groups to obtain the odds ratio (OR) for each HIS item. The mean HIS (+/- SD) was 5.4 +/- 4.5 and differed significantly among the groups (AD, 3.1 +/- 2.5; MID, 10.5 +/- 4.1; mixed, 7.7 +/- 4.3). Receiver-operator characteristic curves showed that the best cutoff was < or = 4 for AD and > or = 7 for MID, as originally proposed, with a sensitivity of 89.0% and a specificity of 89.3%. For the comparison of MID versus mixed the sensitivity was 93.1% and the specificity was 17.2%, whereas for AD versus mixed the sensitivity was 83.8% and the specificity was 29.4%. HIS items distinguishing MID from AD were stepwise deterioration (OR, 6.06), fluctuating course (OR, 7.60), hypertension (OR, 4.30), history of stroke (OR, 4.30), and focal neurologic symptoms (OR, 4.40). Only stepwise deterioration (OR, 3.97) and emotional incontinence (OR, 3.39) distinguished MID from mixed, and only fluctuating course (OR, 0.20) and history of stroke (OR, 0.08) distinguished AD from mixed. Our findings suggest that the HIS performed well in the differentiation between AD and MID, the purpose for which it was originally designed, but that the clinical diagnosis of mixed dementia remains difficult. Further prospective studies of the HIS should include additional clinical and neuroimaging variables to permit objective refinement of the scale and improve its ability to identify patients with mixed dementia.

Brain Ischemia↗