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At least 235 records · Page 13Linked to original sources
PubMed1977

The deficiency of a lysosomal acid hydrolase in two clones derived from the human lymphoblastoid line F137 after mutagen treatment.

Two clones (out of a total of 181 clones tested) derived from the human lymphoblastoid (lymphoid) line F137 after mutagen treatment were found to be deficient in a lysosomal acid hydrolase. The clone N32 derived from EMS-treated F137 is deficient in N-acetyl hexosaminidase A and B but contains normal levels of N-acetyl hexosaminidase C and low levels of an enzyme resembling N-acetyl hexosaminidase S. Thus the enzyme deficiency in this clone appears to resemble the so-called Sandhoff variant of Tay-Sachs disease, a disease inherited as an autosomal recessive condition. The clone G3 derived from MNNG treated F137 is deficient in alpha-galactosidase A. This clone resembles the situation in X-linked Fabry's disease. Karyotype analysis of the clones failed to reveal any chromosome rearrangement or losses of chromosomal material that might have accounted for the mutations and it is suggested that a single point mutation might in each case account for the loss of enzyme activity. No storage of the natural substrates of the two enzymes could be demonstrated in the clones.

Cell Line↗
PubMed1996

Avoiding the pitfalls of EEG interpretation in childhood epilepsy.

The accurate interpretation of the electroencephalogram (EEG) of infants and children being evaluated for suspected epilepsy is based on the appreciation of normal and expected age-dependent characteristics, an awareness of the significance of both epileptiform and non-epileptiform activity, and the correlation of epileptiform abnormalities with clinical findings. Avoiding the pitfalls of pediatric EEG interpretation include the recognition of such normal EEG features in wakefulness as posterior slow waves of youth, mu rhythm, and lambda waves. In addition, the understanding of age-dependent characteristics of EEG state-changes is essential, such as: monorhythmic and paroxysmal hypnagogic hypersynchrony, special features of vertex transients and sleep spindles, positive occipital sharp transients, initial arousal responses and post-arousal hypersynchrony. The EEG response to activation procedures such as hyperventilation and photic stimulation may also be a source of confusion. Patterns of uncertain diagnostic significance also may be present in children, including 14- and 6-Hz bursts and rhythmic temporal theta bursts of drowsiness (the so-called psychomotor variant). Some nonepileptiform EEG abnormalities may also be misinterpreted as epileptiform. The determination of the clinical significance of spike foci and generalized abortive spike-and-wave may pose more of a problem as a potential pitfall than the identification by visual analysis of these interictal discharges. Another problem posed to the electroencephalographer is the determination of the EEG response to antiepileptic drug therapy including effect on spike foci, generalized spike-and-wave and electrical seizure activity, and effect on background activity. The recognition of the differences between the EEG of children and adults will provide the basis for more accurate interpretation and assist the electroencephalographer in avoiding the identification of normal, age-dependent features as epileptiform.

Adolescent↗
PubMed1994

Epidermoid carcinoma arising in Warthin's tumour: a case study.

We present a case of epidermoid carcinoma arising in Warthin's tumour of parotid gland in an 80-year-old woman. Light microscopy revealed small foci typical of benign Warthin's tumour with transition to epidermoid carcinoma. Immunohistochemical and ultrastructural observations confirmed the epidermoid features of the malignant cells. The differential diagnosis of a metastasis from an epidermoid carcinoma to the stroma of Warthin's tumour and also of the so-called metaplastic variant of Warthin's tumour is discussed.

Adenolymphoma↗
PubMed2001

Quantitative analysis of estrogen receptor proteins in rat mammary gland.

Estrogen receptor alpha and beta proteins (ERalpha and ERbeta) at various stages of development of the rat mammary gland were quantified by Western blotting. ERalpha and ERbeta recombinant proteins were used as standards, and their molar concentrations were measured by ligand binding assays. In 3-week-old pregnant, lactating, and postlactating rats the ERalpha content ranged from 0.30-1.55 fmol/microg total protein (mean values). The ERbeta content of the same samples ranged between 1.06-7.50 fmol/microg total protein. At every developmental stage, the ERbeta content of the mammary gland was higher than that of ERalpha. When receptor levels were normalized against beta-actin, it was evident that ER expression changed during development, with maximum expression of both receptors during the lactation period. With an antibody raised against the 18-amino acid insert of the ERbeta variant, originally called ERbeta2 but named ERbetains in this paper, Western blots revealed that ERbetains protein was up-regulated during the lactation period. RT-PCR showed that the levels of messenger RNA of ERbetains paralleled those of the protein. Double immunohistochemical staining with anti-ERalpha and anti-ERbetains antibodies revealed that ERbetains protein colocalized with ERalpha in 70-80% of the ERalpha-expressing epithelial cells during lactation and with 30% of these cells during pregnancy. These observations indicate that expression of ERbetains is regulated not only quantitatively, but also with regard to its cellular distribution. As ERbetains acts as the dominant repressor of ERalpha, we suggest that its coexpression with ERalpha quenches ERalpha function and may be one of the factors that contribute to the previously described insensitivity of the mammary gland to estrogens during lactation.

Actins↗
PubMed1999

Coexpression of alternatively spliced estrogen and progesterone receptor transcripts in human breast cancer.

Primary transcripts of the human estrogen receptor (ER) and progesterone receptor (PR) are subject to a number of alternative splicing events resulting in a range of variant messenger ribonucleic acid species in receptor-positive tissues. Despite in vitro demonstrations of a possible role for some of these variants in hormonal sensitivity, the clinical significance of this process is uncertain. In this study the coexpression of variant ER and PR transcripts has been documented by RT-PCR and Southern blot analysis in a series of receptor-positive breast tumors. In 35 ER-positive tumors, a common profile of variant ER transcripts was present, with all tumors containing the delta2ER and delta7ER, 94% containing the delta4ER, and 83% containing the delta5ER. In 25 of these cases, which were also PR positive, the most highly expressed PR variants, the delta4PR, delta6PR, and delta(4/2)PR, a transcript from which a 126-bp portion of PR exon 4 was deleted, were detected in over 90% of the cases. The alternatively spliced ER variants were expressed at higher relative levels than the PR species, which had mean levels of expression less than 10% that of wild-type PR. The most abundant species was the delta7ER, which was present at levels ranging from 29-83% of the wild type. There was no relationship between the level of delta7ER in individual tumors and the pattern of expression of the estrogen-responsive proteins PR and pS2. The common profile of alternatively spliced ER and PR transcripts in breast tumors means that this feature cannot be used as a discriminator of hormone responsiveness or other clinical end points. Further, the low level of expression of the majority of variant species calls into question their potential for impacting significantly on receptor function.

Adult↗
PubMed1994

Hierarchical regression for epidemiologic analyses of multiple exposures.

Many epidemiologic investigations are designed to study the effects of multiple exposures. Most of these studies are analyzed either by fitting a risk-regression model with all exposures forced in the model, or by using a preliminary-testing algorithm, such as stepwise regression, to produce a smaller model. Research indicates that hierarchical modeling methods can outperform these conventional approaches. These methods are reviewed and compared to two hierarchical methods, empirical-Bayes regression and a variant here called "semi-Bayes" regression, to full-model maximum likelihood and to model reduction by preliminary testing. The performance of the methods in a problem of predicting neonatal-mortality rates are compared. Based on the literature to date, it is suggested that hierarchical methods should become part of the standard approaches to multiple-exposure studies.

Algorithms↗
PubMed2004

Single nucleotide polymorphism-based validation of exonic splicing enhancers.

Because deleterious alleles arising from mutation are filtered by natural selection, mutations that create such alleles will be underrepresented in the set of common genetic variation existing in a population at any given time. Here, we describe an approach based on this idea called VERIFY (variant elimination reinforces functionality), which can be used to assess the extent of natural selection acting on an oligonucleotide motif or set of motifs predicted to have biological activity. As an application of this approach, we analyzed a set of 238 hexanucleotides previously predicted to have exonic splicing enhancer (ESE) activity in human exons using the relative enhancer and silencer classification by unanimous enrichment (RESCUE)-ESE method. Aligning the single nucleotide polymorphisms (SNPs) from the public human SNP database to the chimpanzee genome allowed inference of the direction of the mutations that created present-day SNPs. Analyzing the set of SNPs that overlap RESCUE-ESE hexamers, we conclude that nearly one-fifth of the mutations that disrupt predicted ESEs have been eliminated by natural selection (odds ratio = 0.82 +/- 0.05). This selection is strongest for the predicted ESEs that are located near splice sites. Our results demonstrate a novel approach for quantifying the extent of natural selection acting on candidate functional motifs and also suggest certain features of mutations/SNPs, such as proximity to the splice site and disruption or alteration of predicted ESEs, that should be useful in identifying variants that might cause a biological phenotype.

Alleles↗
PubMed1992

Bronchodilator-resistive cough in atopic patients: bronchial reversibility and hyperresponsiveness.

The number of atopic patients presenting only chronic non-productive cough appears to be increasing. This study was conducted to confirm the existence of non-asthmatic cough associated with atopy. We prospectively examined atopic findings, therapeutic effects of inhaled procaterol, azelastin, and/or glucocorticoids, improvement of FEV1 by bronchodilator therapy and bronchial responsiveness to methacholine in 20 patients. The cough was relieved by inhaled procaterol in 10 patients (Group 2) but not in the other 10 patients (Group 1). The increase in FEV1 by inhaled salbutamol following aminophylline injection was significantly less in Group 1 than in Group 2. Bronchial responsiveness to methacholine was normal in Group 1 while that in Group 2 was hyperreactive. These findings indicate that there is atopic non-asthmatic bronchodilator-resistive cough (Group 1) which is a different entity from bronchodilator-responsive cough (Group 2), or the so-called "cough variant asthma".

Adrenergic beta-Agonists↗
PubMed1999

The cytology of extraskeletal Ewing sarcoma.

BACKGROUND: Extraskeletal Ewing sarcoma (EES) shares histologic, immunohistochemical, and molecular findings with ES of bone. The authors' goal in conducting this study was to examine the cytomorphologic features of EES. In addition, immunocytostaining for CD99/O13 was performed in all cases, and cytogenetic and molecular data were available in about half of the cases. METHODS: The authors studied 20 aspiration cases, all with histopathologic confirmation, and also conducted immunohistochemistry and/or molecular studies. RESULTS: All cases had cellular smears with many single cells and focal clustering. Numerous naked nuclei and focal crush artifacts were seen. Mitosis and necrosis were rare. Four cases had cytoplasmic vacuoles. Five cases showed nuclear molding. Seventeen cases (85%) exhibited small cells with scanty cytoplasm and nuclei with fine chromatin and small nucleoli, representing the so-called typical variant. One case (5%) revealed cells with abundant cytoplasm, large nuclei, and large eosinophilic nucleoli, an example of the atypical or large cell variant. Two cases (10%) had features in between, with cells showing a fair amount of cytoplasm and medium-sized nucleoli, representing the intermediate variant. Nuclear grooves, described as common in the latter, were rare. In all cases, in either cytologic or corresponding histologic material, CD99/O13 immunocytostaining showed strong membranous reactivity. In addition, cytogenetic and/or molecular evidence of ES specific chromosomal translocation was demonstrated in histologic or cytologic material in 10 cases. CONCLUSIONS: EES shows cytologic features similar to ES of bone, with a spectrum of changes ranging from the typical appearance in a majority of cases to intermediate and atypical variants in a minority of cases. CD99/O13 immunocytostaining and/or molecular studies, particularly in the intermediate and atypical variants, may help in establishing a definitive fine-needle aspiration diagnosis, thus avoiding an open surgical biopsy.

12E7 Antigen↗
PubMed1976

Histocompatibility antigens and immune responsiveness; their relevance to rheumatic diseases.

Associations between histocompatibility antigens and human diseases have been found. Some of the highest correlations are with the so-called "rheumatoid variant" disorders. Data gained from ummunogenetic studies in laboratory animals has been invoked in speculation on the significance of the high antigen associations in disease pathogenesis. While much of this data better supports theories on the aetiology of other conditions with less significant antigen associations, it is discussed here with reference to the rheumatic diseases.

Animals↗
PubMed1975

Heterogeneity of human hepatic H-acetyl-beta-D-hexosaminidose. A activity toward natural glycosphingolipid substrates.

A crude soluble preparation of human hepatic N-acetyl-beta-D-hexosaminidase was examined for its activities toward three natural glycosphingolipid substrates after fractionation by the isoelectric focusing procedure. Profiles of activities toward N-acetylgalactosaminyl-galactosyl-glucosylceramide (asialo GM2-ganglioside) and N-acetylgalactosaminyl-galactosyl-galactosyl-glucosylceramide (globoside) were always identical with that of nonspecific N-acetyl-beta-D-hexosaminidase as determined with artificial substrates. The Component A of the enzyme had the activity peak at an isoelectric point of 5.0 to 5.1. In contrast, hydrolytic activities toward N-acetylgalactosaminyl-[N-acetylneuraminyl]galactosyl- glucosylceramide (GM2-ganglioside) were associated with only the most acidic subfraction of the hexosaminidase A component. The activity to hydrolyze GM2-ganglioside had its peak at an isoelectric point of 4.8 to 4.9. These findings might provide an explanation for the GM2-ganglioside accumulation in juvenile GM2-gangliosidosis (partial deficiency of hexosaminidase A) and in the so-called AB variant of GM2-gangliosidosis (apparently normal hexosaminidase A and B activity).

Autopsy↗
PubMed1991

Protein engineering of novel plasminogen activators with increased thrombolytic potency in rabbits relative to activase.

Human tissue-type plasminogen activator (t-PA) is a glycoprotein used currently in thrombolytic therapy for patients with acute myocardial infarction. Due to its rapid rate of clearance from the circulation, continuous intravenous administration of approximately 100 mg over 3 h is recommended. We have previously characterized novel thrombolytic variant forms of t-PA which offer the potential of administration by bolus injection and reduced dosage due to their slower rates of clearance, relative to t-PA. This study was undertaken to quantitatively compare the pharmacokinetics, thrombolytic activity, and hemostatic effects of two of these variant forms, called delta FE1X and delta FE3X plasminogen activator (PA), with commercially available recombinant t-PA (Activase). These evaluations were performed in rabbits after bolus intravenous injection of the proteins. Following injection of 0.25 mg of protein/kg of body weight, the rates of clearance for delta FE3X and delta FE1X PA antigen were decreased approximately 9- and 18-fold, respectively, relative to Activase. Plasma plasminogen activator activity was also measured and the rates of clearance of delta FE3X and delta FE1X PA activity were similarly decreased by approximately 9- and 22-fold, respectively, relative to Activase. To quantitate thrombolytic activity we used the rabbit jugular vein thrombosis model and demonstrated that approximately 50% thrombolysis was achieved with delta FE1X and delta FE3X PA at approximately an 8.6- and 3-fold lower dose than Activase, respectively. No major differences in fibrinogen and alpha 2-antiplasmin depletion were observed among the agents at doses required to produce 50% thrombolysis, indicating similarities in fibrin specificities among these agents. These results demonstrate a reciprocal relationship between thrombolysis and rate of clearance for these thrombolytic proteins. The 8.6-fold increase in potency of delta FE1X PA relative to Activase supports the future clinical testing of this novel engineered protein as a thrombolytic agent.

Animals↗
PubMedDate not supplied

[Electrophoretic and kinetic properties of the erythrocyte glucose-6-phosphate dehydrogenase of patients with hemolytic anemia related to a deficit in the activity of that enzyme].

Partially purified glucose-6-phosphate dehydrogenase (G6PD) was studied in erythrocytes of patients with hereditary hemolytic anemia. Kinetic and electrophoretic properties of G6PD distinctly varied both in patients--homozygotes and in maternal heterozygotes. All the enzymes studied together with the decreased activity possessed the reduced Km value for NADP and G6P. Anomalous enzymes were shown to differ from normal ones by several patterns (pH-dependency, thermostability, % of the substrate analogues utilization, electrophoretic mobility etc). The mutant variant of G6PD was not described earlier. The anomalies variant was called "Kremenchug" to indicate the place of proband origination.

Chemical Phenomena↗
PubMedDate not supplied

[Pharmacologic treatment of constitutional short stature].

The term constitutional short stature is used to describe clinical situations characterized by low stature, assessed using special growth nomograms, but which are not due to specific endocrine alterations, nor to genetic causes or skeletal dysmorphisms, nor secondary to specific organ pathologies or chronic diseases. On the basis of this definition, our paper also includes the so-called normal variants of short stature (familial short stature and constitutional delay of growth) and intrauterine growth retardation. The endocrine and auxological features of constitutional short stature are described in the literature and provide an adequate basis for the use of therapies which include, in addition to growth hormone, substances capable of stimulating the endogenous secretion of the hormone (L-dopa, bromocriptine, clonidine, GHRH, pyridostigmine), or anabolic hormones. Biosynthetic growth hormone therapy is without doubt the most widely used, both on account of the extensive clinical experience and due to the easy availability of the drug made possible by the use of the biosynthetic molecule. Many subjects affected by constitutional short stature show a good response to hGH therapy, whereas others do not benefit by this treatment. New therapies using GHRH and neurodrugs, which are certainly easier to handle and less expensive, represent a new approach to the therapy of constitutional short stature but this condition still requires further investigation.

Dwarfism↗
PubMed1989

[Current aspects of nephrosclerosis].

The most frequent form of nephrosclerosis in human kidneys is the so-called benign variant. It may develop subsequent to even short-lasting hypertensive episodes. The interlobular arteries may be primarily affected, occasionally accompanied by glomerular and tubulointerstitial lesions. Consequently, progressive renal damage may occur potentially aggravating renal diseases of different origin. Malignant nephrosclerosis became a rare disease. Experimentally, it was impossible to induce its early intimal changes exclusively by high blood pressure values. Therefore, it was assumed that previous adaptive vascular changes, in addition to further advancing hypertension, may also be prerequisites for the development of malignant nephrosclerosis.

Humans↗
PubMed1987

[Acanthosis nigricans maligna and Leser-Trélat sign in double malignancy of the breast and stomach].

A female patient with primary cancer of the breast and the stomach developed acanthosis nigricans maligna and Leser-Trélat's sign. Acanthosis nigricans maligna is a well-known cutaneous marker of internal malignancy. It may be intensified by radiotherapy. A variant is called florid cutaneous papillomatosis. Leser-Trélat's sign is a rare cutaneous marker of internal neoplasms. According to the literature, we present 46 patients showing Leser-Trélat's sign. Neither Leser nor Trélat described this sign.

Acanthosis Nigricans↗