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At least 1,135 records · Page 63Linked to original sources
PubMed2004

Characterization of ovarian nuclei with the parameter of power ratio.

The nucleoli and chromatin clumps of ovarian cells contain important features in discriminating malignant cells from normal ones. In geometric properties, the ovarian nucleoli and chromatin clumps appear as irregularly shaped dark spots in the nuclear images from specimens immunohistochemically stained with antibody to Mib-1. Malignant cells often have more active and larger nucleoli and chromatin clumps. However, estimating the size of the nucleoli or chromatin clumps is a difficult task since it is not easy to recognize and accurately separate the regions of nucleoli and chromatin clumps from the rest of the nuclei that are highly irregular and variant in contents and intensities. In this paper, we develop a method to derive a parameter called power ratio that is proportionally related to the size of nucleoli and chromatin clumps based on an ideal nuclear model without the region segmentation of nucleoli or chromatin clumps. Results of characterization of the parameter and comparison between malignant and normal cells are provided.

Algorithms↗
PubMed1993

Comparison of in vitro binding properties of a series of dopamine antagonists and agonists for cloned human dopamine D2S and D2L receptors and for D2 receptors in rat striatal and mesolimbic tissues, using [125I] 2'-iodospiperone.

We investigated the ligand binding properties in vitro of two splice variants of the cloned human dopamine D2 receptor (the 443 and 414 amino acids long forms called D2L and D2S, respectively), expressed in 293 human kidney cells, in comparison with those of the dopamine D2 receptors in rat striatum, nucleus accumbens and tuberculum olfactorium. The new radioligand, [125I]2'-iodospiperone, showed a similar high binding affinity (KD:0.056-0.122 nM) for cloned human D2S and D2L receptors and for the D2 receptors in the three rat brain areas. Binding affinities of 25 dopamine antagonists and of 10 dopamine agonists belonging to different chemical classes were measured. The IC50 values of the antagonists were virtually identical in the five preparations: spiperone was the most potent compound (pIC50 approximately 9.9), remoxipride the least potent one (pIC50 approximately 5.7). The agonists showed similar IC50 values for the cloned human D2S and D2L receptors but their affinity for rat brain D2 receptors was 2- to 5-fold higher. Dopamine showed shallow inhibition curves, the high affinity binding was 10-fold lower for the cloned human D2 receptors than for the rat brain D2 receptors. Addition of stable guanosine-5'-triphosphate (GTP) analogues shifted the D2 receptors in the rat brain tissues to the "low" affinity state, the low affinity binding of dopamine was equal to the affinity for the cloned human receptor. None of the dopamine antagonists or agonists could differentiate between the two splice forms of the cloned human D2 receptors or between the D2 receptors in rat striatal and mesolimbic tissues. The lower apparent affinity of some agonists and of dopamine in the absence of stable GTP analogues suggests a less appropriate receptor G-protein coupling for the cloned human D2 receptors expressed in the 293 human kidney cells. Unexpectedly, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S) reduced the [125I]2'-iodospiperone binding to the D2 receptors by 20-35% in the rat brain tissues and the cloned human D2L receptor, and by 75% to the cloned human D2S receptor. The inhibition in the last case could be prevented partly by submicromolar concentrations of dopamine. The GTP-gamma-S effect is suggested to be due to reduction of disulphide bonds in the receptor. Recent molecular modelling studies indicated an important role of the disulphide bridge between Cys107 at the start of transmembrane domain three and Cys182 in the third extracellular loop, for the binding of dopamine to the D2 receptor.

Animals↗
PubMed2002

The effect of dihydropyrimidine dehydrogenase deficiency on outcomes with fluorouracil.

The use of fluorouracil has been complicated by unpredictable pharmacokinetics, low response rates and seemingly random toxicity. The variable pharmacology is largely due to inherited differences in expression of the metabolising enzyme dihydropyrimidine dehydrogenase (DPD). This converts fluorouracil to inactive metabolites (catabolic pathway) and ultimately dictates the amount of fluorouracil that is available to be metabolised to cytotoxic nucleotides (anabolic pathway). Absolute and partial DPD deficiency affect around 0.1 and 3% of the Caucasian population, respectively. Administration of conventional doses of fluorouracil to these individuals has resulted in profound bone marrow and gastrointestinal toxicity, especially in those with absolute DPD deficiency. Other forms of toxicity such as myocardial ischaemia have been difficult to attribute directly to DPD deficiency. Efforts to improve outcomes with fluorouracil have included monitoring of fluorouracil concentrations and modifying fluorouracil administration techniques (e.g. from bolus injections to protracted intravenous infusions). In general, these moves have met with limited therapeutic advancement. The recognition that DPD deficiency increases toxicity has lead to the suggestion that genotypic or phenotypic assessment of DPD status prior to initiating fluorouracil may help predict outcomes. The gene that encodes for DPD expression is called DPYD. Approximately 1% of Caucasians are heterozygotes for the DPYD*2A mutation which is the variant allele that is most frequently implicated in DPD deficiency. Screening for this mutation may identify around 60% of individuals with absolute DPD deficiency who are at the greatest risk of toxicity. Another approach is to determine DPD activity in peripheral blood mononuclear cells, with low activity suggesting an increased risk of toxicity. Intratumoral DPD activity may also be assessed with high activity suggesting a poorer response to fluorouracil. Recently, drugs that inhibit DPD (e.g. eniluracil) have become available. These remove much of the variability in fluorouracil pharmacokinetics and may make assessment of DPD activity redundant. Despite the considerable inroads that have been made, further study is needed before the best means of optimising fluorouracil treatment is determined.

Animals↗
PubMed2001

Congenital deficiency of 11beta-hydroxysteroid dehydrogenase (apparent mineralocorticoid excess syndrome): diagnostic value of urinary free cortisol and cortisone.

The syndrome of apparent mineralocorticoid excess (AME) is an inherited form of hypertension. This disorder results from an inability of the enzyme 11beta-hydroxysteroid dehydrogenase (11beta-OHSD) to inactivate cortisol to cortisone. The diagnosis of AME is usually based on an elevated ratio of cortisol to cortisone reduced metabolites in the urine [tetrahydrocortisol plus allotetrahydrocortisol to tetrahydrocortisone (THF+alloTHF/THE)]. The principal site of "A" ring reduction is the liver, but AME arises from mutation in the gene encoding 11beta-OHSD2 in the kidney. We used a gas chromatographic/mass spectrometric method to measure the urinary free cortisol (UFF) and free cortisone (UFE) in 24 patients affected by the two variants of AME [19 with the classical form (type I) and 5 with the mild form called AME type II] in order to provide a more reproducible in vivo measure of the renal enzymatic activity. Type I patients were divided into two groups: children under 12 and adults. UFF levels (microg/24 h) did not differ between under-12 controls and AME type I children (mean+/-SD, 9+/-4 and 15+/-12, respectively), but was significantly higher in affected adults compared to controls: (62+/-32 vs 29+/-8, p<0.01). No differences were found between adult controls and AME type II patients (29+/-8 and 37.0+/-14, respectively). UFE was undetectable in 63% of AME type I and significantly lower in AME type II (p<0.05). As a consequence UFF/UFE ratio was significantly higher in AME type I patients both in children and adults compared to controls (AME children: 5.1+/-2.6; normal children: 0.43+/-0.2, p<0.01; AME type I adults: 17.7+/-19.6; normal adults: 0.54+/-0.3 p<0.01). For AME type II, where UFE was detectable in every case, the UFF/UFE ratio was significantly higher than adult controls (2.75+/-1.5 vs 0.54+/-0.3, p<0.01). In conclusion, our study indicates that UFE and UFF/UFE ratio are sensitive markers of 11beta-OHSD2, directly reflecting the activity of the renal isozyme and readily identifying patients with AME. The presence of an altered UFF/UFE ratio in both types of AME, although with different degree of severity, calls for re-evaluation and the classification of AME as a single disorder.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed2000

The effect of arcelin-1 on the structure of the midgut of bruchid larvae and immunolocalization of the arcelin protein.

Some wild accessions of the common bean (Phaseolus vulgaris) contain a family of proteins called arcelins, that are toxic to the larvae of certain bruchid species. Among the six allelic variants of arcelin tested so far, arcelin-5 and arcelin-1 confer the highest level of resistance against the Mexican bean weevil, Zabrotes subfasciatus. The same proteins are not toxic to the bean weevil, Acanthoscelides obtectus, which is also a serious pest of cultivated beans. Arcelins belong to the bean lectin family that includes phytohemaggutinins and alpha-amylase inhibitors. Although homologous to lectins, arcelins are themselves only very weak lectins, and their binding properties have not been clearly established. The toxic properties of arcelins may be related to their recognition of and interaction with the glycoproteins and other constituents of the membranes along the digestive tract of insects. Since arcelin-1 was shown to have growth inhibitory effects for the larvae of Z. subfasciatus but not of A. obtectus, we examined the effect of an arcelin-1 containing diet on the structure of the cells that line the intestinal tract of the larvae of these two bruchid species, and used antibodies against arcelin to examine the distribution of arcelin within the cells and tissues. Here we show that dietary arcelin-1 caused an alteration of the gut structure and the penetration of arcelin into the haemolymph in Z. subfasciatus but not in A. obtectus. These results lead us to suggest that arcelins exert their toxic effect by severely damaging the epithelial cells.

Journal Article↗
PubMed1996

New serotype of Bartonella henselae in endocarditis and cat-scratch disease.

BACKGROUND: The fastidious nature of Bartonella henselae is such that demonstration of clinical infection relies mainly on serological or molecular biological methods. Only five isolates have been obtained from patients with cat-scratch disease (CSD) and none from endocarditis. METHODS: We isolated B henselae from a CSD patient and, for the first time, from a patient with endocarditis. The isolates were characterised on the basis of morphology, biochemistry, cell-wall fatty-acid analysis, PCR-restriction fragment length polymorphism analysis of the 16-23S intragenic spacer region, and 16S rRNA gene sequences. Characterisation of these isolates indicated them to belong to a new serogroup, which we have called "Marseille", and to a new genotype based on the 16S rRNA gene sequence. The new variant was incorporated into an immuno-fluorescence antibody test (IFAT), which was used to reassess serum samples from 113 CSD patients who were seronegative with the conventional IFAT. FINDINGS: 18 (16%) of these apparently seronegative patients yielded significantly raised titres. 20 CSD patients who were seropositive as judged by the conventional IFAT remained seropositive with the new IFAT. INTERPRETATION: Antigenic variability within the species is one possible reason for inconsistent results in the serological diagnosis of CSD.

Adult↗
PubMed2004

Patterns of vocal sharing and social dynamics in a captive group of Campbell's monkeys (Cercopithecus campbelli campbelli).

Although vocal sharing is widespread at several phylogenetic levels, few descriptions concerned primates. The present study involved the dynamics of vocal structures and social organization in a captive group of Campbell's monkeys (Cercopithecus campbelli campbelli) at 3-year periods, using precise sound recording and comparison. The authors focused on combined harmonic 6 calls, often involved in vocal exchanges and associated with approaches. Each female produced 1 to 4 variants, shared, or not, between individuals. Changes appeared between years in the form of disappearance, appearance, or transformation of variants. There was a decrease in the global degree of sharing over the years. Greater changes were observed after social disturbance. Sharing would be more important in disturbed than stable groups to advertise bonds.

Animals↗
PubMedDate not supplied

[Diagnosis of mycobacterioses in the laboratory of the future].

Microscopy is, for various reasons, even today the most important diagnostic measure for pulmonary Tb. With other forms of Tb and with other mycobacterioses there is a considerable increase in importance of the radiometric culture techniques, particularly if these are combined with serologic (ELISA and its variants) or molecular-genetic assays for the presence of mycobacteria. The latter, especially the so called genetic probes combined with the polymerase chain reaction, represent probably the assay of the future for mycobacteria; however, a stern warning must be sounded against the use of such techniques without previous experience in the field of the "classic" mycobacteriology. Serology is, inspite of recent enormous advances, still not capable of producing unequivocal results.

Acquired Immunodeficiency Syndrome↗
PubMed1979

[Variants and developmental anomalies of the odontoid process of the axis].

Clinical and X-ray examination of 140 persons demonstrated a wide range of developmental disorders of the odontoid process, from neglible deviations from the average normal structure to total absence of the process. From the pathogenetic standpoints, some of the variants may be characterized as possessing normal structural features, others are developmental anomalies and defects which call for suboccipital decompression, laminectomy for freeing the compressed bulbarspinal parts of the brain or stabilization of the disturbed craniovertebral relationship.

Adolescent↗
PubMedDate not supplied

[Diagnostic endoscopy in pediatric rhinology].

The paper provides a description on indications to diagnostic endoscopy, its techniques, specific pediatric features, types of anesthesia. Typical complications are specified. Emphasis is placed on local developmental defects of the nasal cavity, lateral wall in particular, as they interfere with natural sinus drainage in many children with chronic and recurrent sinusitis, chronic rhinitis. The tables detail variants of the above deformities with specification of the likely site of stenosis in so-called osteomeatal zone. It is believed that minor surgical correction in the above zone is more preferable than extended radical operations. This seems important in pediatric practice.

Adolescent↗
PubMedDate not supplied

CREST syndrome: a variant of systemic sclerosis.

A variant of systemic sclerosis (scleroderma), CREST syndrome affects a relatively small number of patients. CREST (also called limited cutaneous scleroderma) has a more favorable prognosis than the diffuse form of scleroderma. However, as with most of the connective tissue diseases, the daily issues faced by patients are frequently difficult to manage and require diligent support from the health care team. This article summarizes the clinical manifestations and potential management plan to help the patient cope with this little-understood syndrome. The nursing care model follows a problem-oriented approach for nursing management.

Adaptation, Psychological↗
PubMed2002

Dimerization of the type 4 cAMP-specific phosphodiesterases is mediated by the upstream conserved regions (UCRs).

The cAMP-specific PDE4 family consists of four genes, each expressed as several splice variants. These variants are termed long and short forms depending on the presence or absence of two unique N-terminal domains called upstream conserved regions 1 and 2 (UCR1 and 2). UCR1 and UCR2 have been shown to form a module necessary for the activation of PDE4 upon phosphorylation by the cAMP-dependent kinase (PKA). Here we have uncovered PDE4 oligomerization as a novel function for the UCR1/UCR2 module. Using several different approaches including gel filtration, sucrose density gradient centrifugation, pull-down of differentially tagged PDE constructs, and yeast two-hybrid assay, we show that the long PDE4 splice variant PDE4D3 behaves as a dimer, whereas the short splice variant PDE4D2 is a monomer. Internal deletions of either the C-terminal portion of UCR1 or the N-terminal portion of UCR2 abolishes dimerization of PDE4D3 indicating that both domains are involved in this intermolecular interaction. The dimerization, however, is structurally distinguishable from a previously described intramolecular interaction involving the same domains. PKA phosphorylation and site-directed mutagenesis shown to ablate the latter do not interfere with dimerization. Therefore, dimerization of the long PDE4 forms may be an additional function of the UCR domains that further explains differences in the regulatory properties between the long and short PDE4 splice variants.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1983

Histological type and biological behavior of primary cutaneous malignant melanoma. 2. An analysis of 86 cases located on so-called acral regions as plantar, palmar, and sub-/parungual areas.

Primary cutaneous malignant melanomas are generally divided into 3 separate clinico-pathological variants, lentigo maligna melanoma (LMM), superficial spreading melanoma (SSM), and nodular melanoma (NM). Recently an additional variant, acral lentiginous melanoma (ALM), has been defined, occurring on acral regions, defined as plantar, palmar, and sub-/parungual areas. Histological examination of 86 primary melanomas on acral regions revealed 24 (28%) acral lentiginous melanomas (ALM), 23 (27%) superficial spreading melanomas (SSM), 18 (21%) nodular melanomas (NM), and 21 (24%) unclassifiable melanomas. No LMM was seen. The prognosis was found to be the same in patients with SSM and ALM. However, by correlating histological type with frequency of antecedent nevus, duration of melanoma and dominant invasive tumor cell, it was demonstrated that histologically typical ALM differed from histologically typical SSM by their infrequent origin from antecedent nevi, their lower local growth rate, and their more frequent content of spindle cells. These findings support ALM as a valid melanoma subtype only when clearly defined histologically.

Female↗
PubMed1990

Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy.

The lysosomal degradation of sulfatide requires the specific enzyme, arylsulfatase A, as well as a heat stable protein called sphingolipid activator protein-1 (SAP-1). While most patients with metachromatic leukodystrophy have defects in arylsulfatase A, some patients have defects in SAP-1. SAP-1 is coded for by a gene on human chromosome 10 that also codes for three other proposed SAP. Examination of the cDNA from two siblings with SAP-1 deficiency revealed a point mutation of nucleotide #650 (counting from the initiation ATG) which is in the SAP-1 coding domain. This C to T transition changed the codon from threonine (ACC) to one coding for isoleucine (ATC). This eliminated the only glycosylation site in mature SAP-1 and could explain the findings made at the protein level.

Base Sequence↗
PubMed1990

Molecular cloning and nucleotide sequence of another variant of the Escherichia coli Shiga-like toxin II family.

Escherichia coli strain H.I.8 (O128:B12) produces low levels of a Shiga-like toxin (SLT) which we have called SLTIIva because of its close relationship with SLTIIv. The Vero cell cytotoxicity of SLTIIva is neutralized by antisera against SLTII and SLTIIv but not by antisera against SLTI. These data indicate that the SLT of strain H.I.8 is a member of the SLTII family. Since SLTIIva shares with SLTIIv the property of having low cytotoxicity to HeLa cells compared with Vero cells, it is appropriate to consider both toxins as variants of SLTII. SLTIIva differs from SLTIIv in that it is more heat-stable. Further, SLTIIv-producing strains of E. coli have only been isolated from pigs while the SLTIIva-producing E. coli strain examined in this study was isolated from a human infant with diarrhoea. The genes for this SLT were cloned from a cosmid library of total cellular DNA by screening recombinants for Vero cell toxicity and with a DNA probe derived from SLTIIv structural genes. Nucleotide sequence analysis was performed on a 2.0 kb AvaII-HincII fragment which encodes the toxin gene. The nucleotide sequence data confirm the close relationship between SLTIIva and SLTIIv: they have 98% nucleotide sequence homology in the B subunit gene and 70.6% homology in the A subunit gene. Comparison of DNA sequences indicated that SLTIIva was most closely related to SLTIIv, closely related to SLTII and less closely related to SLTI.

Amino Acid Sequence↗
PubMed1981

A method of screening for growth hormone deficiency using anthropometrics.

Among children less than 3rd percentile in height, less than 1% are deficient in endogenous growth hormone, while 80% have no recognizable organic cause for short stature, and are termed normal variants. This study investigated whether anthropometric evaluation can distinguish growth hormone-deficient from normal variant children. Height, weight, midarm circumference and 10 skinfold thicknesses were measured in 24 growth hormone-deficient and 26 normal variant children; indices of linear growth, adiposity, and lean body mass were derived from these. All these variables were analyzed statistically by discriminant analysis. This led to a screening formula, here called a "Z-function," based only on height and five skinfolds (abdomen, back, chest, knee, and calf). The Z-function classified correctly all but two growth hormone-deficients and two normal variants. Because of the small and possibly inhomogeneous sample, the particular formula developed here is not recommended for general use, but these preliminary findings show that a simple anthropometric screening test is indeed feasible, and could be useful in pediatric practice.

Adipose Tissue↗
PubMed1984

Transferrin subtypes and variants in Germany; further evidence for a Tf null allele.

Isoelectric focusing (IEF) with carrier ampholytes was used for the determination of transferrin C subtypes and transferrin B and D variants in a sample of 1125 unrelated individuals from Southern Germany. The observed TfC allele frequencies were Tf*C1 = 0.7872, Tf*C2 = 0.1365, and Tf*C3 = 0.0675. The rare C subtype C6 was observed twice. A new C subtype, called C10, was observed and identified by IEF with immobilized pH gradients. The rare C subtypes C4 and C8 were also studied by this method. TfB and TfD variants were found with a heterozygous frequency of 1.53%. One new TfD was found which is located between D1 and D2 and therefore named D1-2. Evidence for a Tf null allele was obtained in a child and the putative father; they were considered to be heterozygous for an allele Tf0. The theoretical exclusion rate for paternity examinations was calculated for the Tf system and found to be 17.95%.

Alleles↗