PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “pathological subtype”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources

Immunohistochemical expression of hormone receptors in invasive breast carcinoma: correlation of results of H-score with pathological parameters.

The results of H-scores of oestrogen and progesterone receptor (ER and PR) expression in 150 invasive breast cancers were correlated with conventional pathological prognostic parameters: tumour size, histological grade and subtype, lymph node status, lymphovascular invasion, Nottingham Prognostic Index (NPI) and pathological stage. ER and PR status was determined by immunohistochemical staining of sections cut from archival paraffin-embedded tissue blocks. We defined positive receptor expression as a H-score of 50 and above. Our findings revealed ER and PR positivity in 98 (65%) and 52 (35%) cases, respectively. Fifty-one (34%) ER-positive cases also showed PR expression, while 51 (34%) tumours were negative for both ER and PR. Positive expression for ER and PR was significantly correlated with histological grade (P < 0.0005), mitotic score (P < 0.05) and nuclear pleomorphism (P < 0.05). When we used the relatively simpler method of a cut off of at least 10% tumour cell nuclear staining of moderate or greater intensity as positive receptor status, we found that it agreed well with results of the H-score, a more quantitative method of assessment.

Adult↗

Age variation in Hodgkin's disease risk factors in older women: evidence from a population-based case-control study.

Hodgkin's disease (HD), which affects all age groups, has been associated with childhood social class, particularly among adults under age 40. Little is known about social class risk factors in older adults, and the few existing studies have conflicting findings. As part of a population-based case-control study of HD in women, we examined social class risk factors by diagnostic age groups (45-54 years and 55-79 years) corresponding to incidence patterns and by histologic subtypes based on a uniform pathologic review. Among women ages 45-54, cases were more likely to be Catholic, to have lower income and to be taller than controls. Among women ages 55-79, cases tended to have come from small or large childhood households, lived in single-family childhood housing, and had a single rather than shared bedroom at age 11. For the nodular sclerosis (NS) histologic subtype, similar age differences in risk factors were apparent. Comparisons between the NS and non-NS subtypes in women ages 55-79 identified some common risk factors (single-family childhood home, single bedroom at age 11) but others specific to one subtype (childhood household size, adult height for NS; lower maternal education for non-NS). Thus, some social class associations with HD differed between middle-aged and older women, as well as between these groups and younger adults, while others were shared across age groups. Risk also was associated with both higher and lower childhood social class in middle-aged and older women, in contrast with previous findings. None of these patterns was explained entirely by histologic subtype but may reflect age and histology subtype variation in the HD-EBV association.

Age Factors↗

Gene expression profiling identifies molecular subtypes of gliomas.

Identification of distinct molecular subtypes is a critical challenge for cancer biology. In this study, we used Affymetrix high-density oligonucleotide arrays to identify the global gene expression signatures associated with gliomas of different types and grades. Here, we show that the global transcriptional profiles of gliomas of different types and grades are distinct from each other and from the normal brain. To determine whether our data could be used to uncover molecular subtypes without prior knowledge of pathologic type and grade, we performed K-means clustering analysis and found evidence for three clusters with the aid of multidimensional scaling plots. These clusters corresponded to glioblastomas, lower grade astrocytomas and oligodendrogliomas (P<0.00001). A predictor constructed from the 170 genes that are most differentially expressed between the subsets correctly identified the type and grade of all samples, indicating that a relatively small number of genes can be used to distinguish between these molecular subtypes. These results further define molecular subsets of gliomas which may potentially be used for patient stratification, and suggest potential targets for treatment.

Astrocytoma↗

The plasticity-pathology continuum: defining a role for the LTP phenomenon.

Long-term potentiation (LTP) is the most widely studied form of neuroplasticity and is believed by many in the field to be the substrate for learning and memory. For this reason, an understanding of the mechanisms underlying LTP is thought to be of fundamental importance to the neurosciences, but a definitive linkage of LTP to learning or memory has not been achieved. Much of the correlational data used to support this claim is ambiguous and controversial, precluding any solid conclusion about the functional relevance of this often artificially induced form of neuroplasticity. In spite of this fact, the belief that LTP is a mechanism subserving learning and/or memory has become so dominant in the field that the investigation of other potential roles or actions of LTP-like phenomena in the nervous system has been seriously hindered. The multiple subtypes of the phenomena and the myriad molecules apparently involved in these subtypes raise the possibility that observed forms of LTP may represent very different types of modification events, with vastly different consequences for neural function and survival. A relationship between LTP and neuropathology is suggested in part by the fact that many of the molecular processes involved in LTP induction or maintenance are the same as those activated during excitotoxic events in neurons. In addition, some LTP subtypes are clearly induced by pathological stimuli, e.g., anoxic LTP. Such data raise the possibility that LTP is part of a continuum of types of neural modification, some leading to beneficial alterations such as may occur in learning and others that may be primarily pathological in nature, as in kindling and excitotoxicity. In this article, we introduce a plasticity-pathology continuum model that is designed to place the various forms of neural modification into proper context. In vitro and kindling receptor regulation studies are used to provide a basis for evaluating the specific synaptic/cellular response modification along the continuum of events, from beneficial to detrimental, that will be induced by a particular stimulus.

Animals↗

Neuropathology of amyotrophic lateral sclerosis with extra-motor system degeneration: characteristics and differences in the molecular pathology between ALS with dementia and Guamanian ALS.

Amyotrophic lateral sclerosis (ALS) is classified into distinct subtypes mainly based on clinicopathological features, in addition to epidemiologic and genetic backgrounds. In addition to sporadic ALS with classical pathology, characteristics in the clinical features, in the histological findings and their topographical distribution, and in the molecular pathology, especially the intracytoplasmic neuronal inclusions, enable us to identify the following subtypes: ALS with dementia (ALS-D), ALS in the Western Pacific, ALS with multi-system degeneration, familial ALS, and superoxide dismutase 1-linked ALS. These subtypes not infrequently exhibit various types of extra-motor system degeneration, and even multi-system pathology. Some of the subtypes (for instance ALS-D or familial ALS) can be deduced, to a certain extent, from characteristic neuronal inclusions such as ALS-type ubiquitinated inclusions, Lewy body-like hyaline inclusions (LBHIs), or ubiquitinated intracytoplasmic neuronal inclusions as typically seen in the dentate fascia. The purpose of this article is to clarify the molecular pathogenesis of the cerebral cortex in ALS-D and Guamanian ALS and parkinsonism-dementia complex (PDC), in order to elucidate the relationship and distinction between these two subtypes. As indicated previously, investigations on ubiquitin-immunoreactivity in the hippocampus further support the view that the pathology of G-ALS/PDC may be that of a tau-related tangle disorder, whilst ALS-D has a feature of the motor neuron disease type-frontotemporal dementia.

Amyotrophic Lateral Sclerosis↗

[Subtypes of serum group specific component (Gc) in normal conditions and in pathology].

In the framework of the ecogenetic research programme, the data are presented on the genetic polymorphism of the vitamin D-binding protein (Gc) in various USSR populations. Blood serum samples were studied, taken from the Russians of the town Yegorievsk, Moscow Region (p = 321) and 113 Russian patients with tuberculosis using the method of isoelectrofocusing. The information was obtained of the Gc frequencies in two population units of Buryats of Aginsky and Ost-Ordynsky Autonomous Districts of Chita and Irkutsk Regions, including the Olkhon island (on the lake Baikal), in totality, 593 individuals and 13 local groups. The position of the studied Russian and Buryat groups within the gene frequency co-ordinate space is well in line with the estimated area of their localization, with regard to the world distribution. Among the Buryat populations studied, there is distinct heterogeneity for which the factor Gc1F plays a leading role within the Gc system/responsible for 92% of all possible genetic variability. Gc factor frequencies in Buryats range within the following limits: 1F.-0.3864-0.6023, 1S-0.1895-0.4535, 2-0.1364-0.2581. For the Russians of Yegorievsk and the patients with tuberculosis of Moscow and Moscow Region following allele frequencies are established: 1-F0.1169, 1S-0.5476, 2-0.1364 and 1F-0.1106, 1S-0.5531, 2-0.3363, respectively, which indicates that no association exists between Gc variants and tuberculosis. The correlation of the Gc allele frequency distribution with the ratio of insulin-independent diabetes (type 2) world-wide indicates that expression of high frequency of diseases is accompanied with comparatively rare characteristic combination of frequencies of three Gc alleles.

Alleles↗

Estrogen receptors (ERalpha/ERbeta) in normal and pathological growth of the human myometrium: pregnancy and leiomyoma.

The distributions of the mRNAs for estrogen receptors (ERalpha and ERbeta) and their binding properties in myometria of pregnant and nonpregnant women and in leiomyoma were studied. RT-PCR analysis indicated that the term pregnancy myometria had little ERalpha mRNA, whereas the amounts of ERbeta mRNAs in pregnant or nonpregnant myometria appeared to be similar. Both ERalpha and ERbeta mRNA were greater in certain leiomyoma than in normal nonpregnant myometria. The binding kinetics revealed that two specific binding sites (with high or low affinity) for 17beta-estradiol were present in the nonpregnant myometrium. Only the low-affinity binding sites were detectable in late-pregnancy myometria and in leiomyoma, and their capacities were increased two- to threefold (P < 0.001) in leiomyoma. The pregnancy- and leiomyoma-related changes in myometrial ER status, especially the low concentration of ERalpha mRNA and the lack of high-affinity ER in pregnant women, plus the increased ERalpha and ERbeta mRNAs and the increased low-affinity ER in some leiomyoma, suggest that the redistribution of ER subtypes is associated with the pathological and/or normal growth of the myometrium.

Female↗

Morphological heterogeneity of CA1 pyramidal neurons in response to ischemia.

We have found, based on the electrophysiological properties, two subtypes of CA1 pyramidal neurons in the CA1 region of the normal hippocampus, late postsynaptic potential (L-PSP) neurons and non-L-PSP neurons. In addition, our previous study has shown that the electrophysiological properties of these two subtypes of pyramidal neurons were differentially modified after ischemia. In the present study, we hypothesized that ischemia might also induce different morphological alterations in these two subtypes of neuron. To test the hypothesis, we compared the changes in the dendritic arborization and soma volume of these two subtypes of neurons in rats subjected to transient global ischemia. We found a significant decrease in the basal dendritic length of L-PSP neurons at 12 hr after reperfusion, resulting mainly from a significant decrease in the dendrite terminal length. The apical dendritic length of L-PSP neurons markedly increased at 24 hr after ischemia, resulting mainly from an increase in the number of branching arbors in the middle part of the apical dendritic trees. The soma size of L-PSP neurons was significantly reduced at 12 hr, but they became slightly larger at 24 hr and 48 hr after reperfusion. In contrast to L-PSP neurons, non-L-PSP neurons showed slight modifications in the dendritic arborization but had persistent swelling of their soma after ischemia. These results indicate that pathological changes in these two subtypes of neurons are different after ischemia.

Animals↗

Estrogen receptors alpha and beta in the female reproductive tract of the rat during the estrous cycle.

The action of steroid hormones is primarily mediated via a process that involves hormone binding to specific receptors in target cells, which leads to transcriptional activation of steroid-responsive genes and, subsequently, to a modification of cellular responses. The aim of the present study was to obtain information about the dynamics of the two types of estrogen receptors (ERs), alpha and beta, by comparing their concentration and distribution in the reproductive tract of the rat during the estrous cycle. Twenty-four 55- to 60-day-old female Sprague-Dawley rats were used. The stage of estrous cycle was determined by vaginal smear. ERalpha was the dominating subtype in uterus, oviduct, and cervix/vagina, with the distribution varying in stroma and epithelium during the estrous cycle. A low level of ERalpha mRNA was observed in ovarian stromal cells, with some scattered positive cells found among granulosa cells. ERbeta expression was observed in the different compartments of uterus and cervix/vagina, but cyclic variation during the estrous cycle was less evident than that of ERalpha. Only a few scattered cells that contained ERbeta mRNA were observed in oviduct. ERbeta mRNA was highly expressed in granulosa cells of developing follicles, with a weaker hybridization signal in new corpora lutea. Immunohistochemistry showed that protein levels of ERalpha and ERbeta have distinct specificity for tissues and cell types, similar to their respective levels of mRNA, as assessed by in situ hybridization. The precise physiological function and importance of ERbeta is still unclear. The relative physiological and pathological function of each ER subtype in the female reproductive tract remains to be further evaluated.

Animals↗

Spinocerebellar degenerations in Japan: a nationwide epidemiological and clinical study.

A nationwide survey of patients in Japan with spinocerebellar degenerations (SCD), including SDS and SND, was conducted from 1988 to 1989. The survey consisted of two parts. The first revealed that the estimated total number of patients with SCD in Japan was 5,050 (range: 4,100-6,000) with an estimated prevalence of 4.53 per 100,000 in 1987. The second part investigated the neurological and functional status of patients with SCD. The percentages of those belonging to each subtype of SCD were: OPCA; 34.4%, LCCA; 15.2%, MHCA; 12.6%, HHCA; 7.5%, SDS; 7.0%, HSP; 3.9%, DRPLA; 2.5%, FA; 2.4%, MJD; 2.0% and SND; 1.5%. Compared with European epidemiological studies Japan had a higher proportion of non-hereditary types of SCD. Various clinical features of SCD subtypes were compared grouped by pathological lesion and heredity. HHCA and LCCA: cerebellar ataxia predominated in all stages, and neurological signs other than cerebellar ataxia were rare. MHCA, DRPLA and MJD: in the early phase ataxia was the most common symptom in MHCA, the AC form of DRPLA and MJD, but ataxia was less common and chorea or epilepsy were often observed in ME and PH forms of DRPLA. Other frequently observed clinical features were parkinsonian rigidity in MHCA, abnormal movements and posture in DRPLA and MJD, and disturbances of eye movements in MHCA, the AC form of DRPLA and MJD. OPCA, SDS and SND: dominant clinical features were cerebellar ataxia in OPCA, autonomic disturbance in SDS, and parkinsonian rigidity in SND. FA and HSP: both were rare in Japan. Clinical features related to supra-supinal lesions were frequently observed in FA. Functional status of SCD: the severity of illness was significantly associated with the level of independence in each item of ADL. Activities not requiring dynamic balance were performed independently for a longer period than those requiring dynamic balance. Among SCD subtypes, functional prognosis was poorest in non-hereditary, multi-systemic types (OPCA, SDS and SND) followed by hereditary multi-systemic types (MHCA, DRPLA and MJD), and better in spinal types (FA and HSP) and cerebellar types (HHCA and LCCA).

Activities of Daily Living↗

Pathologic splenic rupture as the presentation of mantle cell lymphoma.

Pathologic splenic rupture in non-Hodgkin's lymphoma (NHL) is a rare event, with 32 cases previously reported. Initial presentation of NHL with this complication is even rarer. We report such a case in an 80-year-old man with mantle cell lymphoma (MCL). It is notable that of the previously reported cases of pathologic rupture, three have occurred in MCL, suggesting that patients with this uncommon subtype of NHL may be particularly vulnerable to pathologic splenic rupture. Following splenectomy the patient's disease behaved in a high-grade fashion. Despite an initially encouraging response, his disease ran an aggressive course and he succumbed within four months. This case demonstrates the presentation of MCL with pathologic splenic rupture, as well as the potentially highly malignant behaviour of the disease.

Aged↗

Roles of endothelin ETA and ETB receptors in the pathogenesis of monocrotaline-induced pulmonary hypertension.

The functional roles of endothelin ETA and ETB receptors in the development of monocrotaline (MCT)-induced pulmonary hypertension were investigated using MCT-treated rats in the absence or presence of a daily administration of A-192621, a selective ETB receptor antagonist, ABT-627, a selective ETA receptor antagonist, or a combination of both drugs. Four weeks after the injection of saline or MCT (60 mg/kg, s.c.), cardiac hypertrophy, right ventricular systolic pressure and morphologic changes of pulmonary arteries were evaluated. Compared with the control animals, MCT produced marked pulmonary hypertension associated with increases in right ventricular pressure and hypertrophy, and pulmonary arterial medial thickening. These MCT-induced alterations were markedly suppressed by daily treatment with ABT-627 for 4 weeks (10 mg/kg/d, twice daily), whereas treatment with A-192621 significantly aggravated the above MCT-induced pathologic changes. The blockade of both receptor subtypes by a combination of A-192621 and ABT-627 also significantly improved the MCT-induced pathologic changes, to the same extent as with ABT-627 administration. Thus, an exaggerated response to MCT during ETB receptor blockade also seems to be mediated by ETA receptor activation, thereby suggesting that ETA receptor-mediated action is exclusively contributive to the pathogenesis of MCT-induced pulmonary hypertension, although we cannot rule out a protective role of ETB receptor-mediated action.

Administration, Oral↗

Fatal familial insomnia and familial Creutzfeldt-Jakob disease: clinical, pathological and molecular features.

Fatal familial insomnia (FFI) and a subtype of familial Creutzfeldt-Jakob disease (CJD178) are two prion diseases that have different clinical and pathological features, the same aspartic acid to asparagine mutation (D178N) at codon 178 of the prion protein (PrP) gene, but distinct genotypes generated by the methionine-valine polymorphism at codon 129 (129M or 129V) in the mutant allele of the PrP gene. The D178N, 129M allele segregates with FFI while the D178N, 129V allele segregates with CJD178. The proteinase K resistant PrP (PrPres) isoforms present in FFI and CJD178 differ in degree of glycosylation and size. Thus, the amino acid, methionine or valine, at position 129 of the mutant allele, in conjunction with D178N mutation results in significant alterations of PrPres in FFI and CJD178. The 129 polymorphic site also exerts influence through the normal allele: the course of the disease is shorter in the patients homozygous at codon 129 and other minor but consistent phenotypic differences occur between homozygous and heterozygous FFI patients. The comparative study of PrPres distribution in FFI homozygotes and heterozygotes at codon 129 has lead to the conclusion that the phenotypic differences observed between these two FFI patient populations may be the result of different rates of conversion of normal PrP into PrPres, at least in some brain regions.

Adult↗

Is it feasible to diagnose germ-cell tumors by fine-needle aspiration biopsy?

Fine needle aspiration biopsy is an extremely useful procedure for the diagnosis of germ cell tumors. Most of the subtypes can be easily recognized and differentiated from other subtypes. For difficult cases clinical pathologic correlation may be extremely helpful in establishing a precise diagnosis. Mixed germ cell tumors may cause some difficulty if one of the components is predominant. Immunohistochemistry may also play an important role in arriving at a definitive diagnosis.

Biopsy, Needle↗

Basic and clinical neuroscience applications of embryonic stem cells.

There have been recent dramatic advances in our understanding of the molecular mechanisms governing the elaboration of mature tissue-specific cellular subpopulations from embryonic stem (ES) cells. These investigations have generated a range of new biological and potential therapeutic reagents to allow us to dissect specific stages of mammalian development that were previously experimentally inaccessible. Ultimately, we will be able to reconstitute seminal signaling pathways to promote regeneration of the nervous system. Totipotent ES cells possess an unlimited proliferative capacity that make them attractive candidates for use in a series of innovative transplantation paradigms. Elucidation of the molecular and physiologic properties of ES cells also has important implications for our understanding of the integrative cellular processes underlying neural induction, patterning of the neural tube, neural lineage restriction and commitment, neuronal differentiation, regional neuronal subtype specification, and the specific pathological consequences of alterations in discrete components of these fundamental neurodevelopmental pathways. In addition, recent experimental observations suggest that neurodegenerative disease pathology may involve alterations in a range of progressive neural inductive and neurodevelopmental events through novel biological mechanisms that result in sublethal impairments in cellular homeostasis within evolving regional neuronal precursor populations containing the mutant proteins, culminating in increased vulnerability of their differentiated neuronal progeny to late-onset apoptosis. Future discoveries in ES cell research will offer unique conceptual and therapeutic perspectives that representing an alternative to neural stem cell therapeutic strategies for ameliorating the pathologic consequences of a broad range of genetic and acquired insults to the developing, adult, and aging brain. Evolving regenerative strategies for both neurodevelopmental and neurodegenerative diseases will likely involve the targeting of vulnerable regional neural precursor populations during "presymptomatic" clinicopathological stages prior to the occurrence of irrevocable neural cell injury and cell death.

Animals↗

Ultrastructural study of periodic lamellar granules in human neutrophils.

Granules consisting of periodically arranged membranous lamellae and amorphous electron-opaque material, i.e., periodic lamellar granules, are present in human neutrophils. To date, no extensive ultrastructural studies have been carried out on these granules because of their infrequent presence in neutrophils. The bone marrow of 18 cases of chronic myeloproliferative disorders, including one case of chronic neutrophilic leukemia in which periodic lamellar granules were frequently seen in neutrophils, was investigated by electron microscopy. Periodic lamellar granules were seen in neutrophils in 12 of the 18 cases at varying frequencies. They were preferentially seen in immature neutrophils. The transverse profiles of these granules revealed concentric complete/incomplete rings or periodic parallel straight lines, i.e., various patterns of lamellar arrangement were present. Periodic lamellar granules were positive for myeloperoxidase and lysozyme at the electron-microscopic level. These results suggest that these granules represent a primary neutrophil granule subtype. However, their functional and pathologic significance remains unknown.

Cytoplasmic Granules↗

Frontotemporal dementia.

Frontotemporal dementia (FTD) and related conditions are often considered daunting because of the numerous inter-related clinical syndromes and their apparently heterogeneous pathologic substrates. Although the labyrinthine complexity of the disease seemingly continues to grow, recent discoveries have made the maze of FTD somewhat more navigable, spurring new interest in the field. This review begins by surveying the fascinating clinical presentations of these conditions and the few currently available treatments, then turns to recent progress in understanding the pathophysiology of FTD. Among the important advances surveyed are clinicopathologic correlations that enable prediction of the pathologic substrate of certain clinical subtypes, and genetic studies that have been particularly fruitful in identifying new causes of FTD.

Dementia↗

The behavioural and neurochemical profile of the putative dopamine D3 receptor agonist, (+)-PD 128907, in the rat.

The functional relevance of the dopamine D3 receptor is still unresolved, largely because of the absence of selective D3 receptor ligands. In the present study we have examined the in vivo profile of (+)-PD 128907, a potent and functionally selective D3 receptor agonist. Low doses of (+)-PD 128907 reduced spontaneous locomotor activity in the rat (ED50 = 13 +/- 3 micrograms/kg, s.c.) a response which was comparable with the non-selective D2,3 receptor agonist apomorphine (ED50 = 13 +/- 1.6 micrograms/kg, s.c.). In addition (+)-PD 128907 impaired prepulse inhibition of the acoustic startle response, with significant effects observed at doses of 30 micrograms/kg when appropriate prepulse intensities were used. Higher doses reversed gamma-butyrolactone-induced catecholamine synthesis (ED50 = 95 +/- 22 and 207 +/- 37 micrograms/kg in accumbens and striatum respectively) and induced yawning (100-300 micrograms/kg), penile grooming (30-1000 micrograms/kg) and sniffing (> or = 300 micrograms/kg) although doses 3- to 10-fold greater than apomorphine were required to produce maximal effects. In contrast to apomorphine, however, (+)-PD 128907 failed to induce intense stereotyped licking and biting in the rat. In view of the potency and selectivity of (+)-PD 128907 for the D3 receptor, a role in the control of locomotor activity is suggested. In addition, the observation that (+)-PD 128907 disrupts prepulse inhibition, a phenomenon which is also impaired in schizophrenic subjects, may indicate the pathological importance of this receptor subtype.

4-Butyrolactone↗