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Genetic heterogeneity of factor XIII deficiency: first description of unstable A subunits.

In previously reported cases, congenital deficiency of coagulation factor XIII has been found to result from the absence of the enzymatically active A subunits. In the family reported here two members were found to be heterozygous for an unstable A subunit which, in the homozygous state, or in the heterozygous state with the previously described null allele, would be expected to result in factor XIII deficiency. The implications that this new variant has on heterozygote screening are discussed.

Alleles↗

Renal cysts and diabetes syndrome linked to mutations of the hepatocyte nuclear factor-1 beta gene: description of a new family with associated liver involvement.

BACKGROUND: Mutations in the hepatocyte nuclear factor (HNF)-1beta gene (TCF2) are responsible for a syndrome characterized by maturity-onset diabetes of the young, a nondiabetic renal disease, genital malformations, and liver dysfunction. METHODS: The HNF-1beta gene was screened for mutations in four members of an Italian family with early-onset, nonketotic diabetes or a familiar, nondiabetic renal disease and nonprogressive liver disorder. RESULTS: The genetic analysis revealed an already described nonsense mutation in codon 177 of HNF-1beta gene (R177X) in the four related subjects. Clinical features included diabetes in three of four patients, monolateral renal hypoplasia with cysts in the controlateral kidney in two patients, and bilaterally small hyperechoic kidneys without cysts in the other two patients. Renal function impairment was severe in one patient, requiring dialysis treatment, and mild in three. Three patients had nonprogressive liver dysfunction, with long-lasting enzyme alterations but no liver insufficiency or jaundice. CONCLUSION: HNF-1beta gene mutations are associated with a wide variability in severity and pattern of clinical symptoms within the same kindred regarding diabetes and renal impairment. Moderate liver dysfunction may be a so far overlooked component of the syndrome.

Adult↗

Chemotherapy medication errors: descriptions, severity, and contributing factors.

PURPOSE/OBJECTIVES: To expand the limited body of knowledge of medication errors involving chemotherapy. DESIGN: Exploratory, descriptive. SAMPLE: 160 (26%) of 620 randomly selected Oncology Nursing Society members employed in direct patient-care positions and 26 nonmembers with chemotherapy administration responsibilities employed in different settings. METHODS: Mailed investigator-developed questionnaire containing 24 demographic and open-ended questions. MAIN RESEARCH VARIABLES: Nurses' descriptions of the nature and severity of chemotherapy medication errors. FINDINGS: Chemotherapy medication errors were reported to have occurred in the workplace of 63% of the respondents, and 140 errors were described. Errors included under- and overdosing, schedule and timing errors, wrong drugs, infusion-rate errors, omission of drugs or hydration, improper preparation of drugs, and chemotherapy given to the wrong patients. Stress, understaffing, lack of experience, and unclear orders were cited as factors believed to contribute to the occurrence of the errors. Most of the errors were reported internally, but only 3% were known to be reported to national reporting databases or drug manufacturers. CONCLUSIONS: Chemotherapy medication errors are not uncommon and infrequently are reported externally to databases or manufacturers. IMPLICATIONS FOR NURSING PRACTICE: Risk management strategies to promote safe chemotherapy administration include comprehensive chemotherapy administration training, adherence to basic principles of medication administration, and adequate staffing. Oncology nurses need to know how and when to report chemotherapy medication errors to national databases and drug manufacturers.

Antineoplastic Agents↗

Polymorphism of properdin factor B in Japanese. Description of a rare variant and data of association with HLA and C2.

Polymorphism of the properdin factor B (BF) was investigated using an agarose gel immunofixation electrophoresis in 487 unrelated healthy adult Japanese who were already typed for HLA-A, -B, -C and C2. Besides the previously reported phenotypes in Japanese (S, FS, and F), a rare heterozygous phenotype (tentatively maned FTS) was observed once. The estimated allele frequencies for BS*S, BF*F, and FB*FT (F Tokyo) were 0.801, 0.198, and 0,001 respectively. The relative electrophoretic mobility of the variant band of type FTS was measured by Dr. G Mauff to be F 0.75. The conversion fragment Bb of the type showed a double-banded pattern. BF hemolytic activity of the FTS individual was at the same level as other phenotypes. Statistical tests for the phenotypic data of BF with HLA-A, -B, -C, and C2 indicated the presence of the following significant associations in Japanese: Aw33-BF*F, A11-BF*S, Aw24-BF*S, B15-BF*F, B17-BF*F, Bw44-BF*F, B7-BF*S, Bw52;-BF*S, BW54-BF*S, BW59-BF*S, Cw3-BF*F, C2*AT-BF*F, and C2*A'-BF*F.

Adult↗

[Valve of detection of the Du blood group factor in hospital transfusion practice].

Following a description of factor Du, a variant of factor D, a personal series of about 3% is described and the technique using indirect Coombs test is indicated. Identification of factor Du takes on importance in the prophylaxis of post-transfusional isoimmunization as donors of Rh negative blood with Du positive must be considered Rh positive donors.

Blood Group Incompatibility↗

Modeling transcription factor binding sites with Gibbs Sampling and Minimum Description Length encoding.

Transcription factors, proteins required for the regulation of gene expression, recognize and bind short stretches of DNA on the order of 4 to 10 bases in length. In general, each factor recognizes a family of "similar" sequences rather than a single unique sequence. Ultimately, the transcriptional state of a gene is determined by the cooperative interaction of several bound factors. We have developed a method using Gibbs Sampling and the Minimum Description Length principle for automatically and reliably creating weight matrix models of binding sites from a database (TRANSFAC) of known binding site sequences. Determining the relationship between sequence and binding affinity for a particular factor is an important first step in predicting whether a given uncharacterized sequence is part of a promoter site or other control region. Here we describe the foundation for the methods we will use to develop weight matrix models for transcription factor binding sites.

Algorithms↗

[E3N, a cohort study on cancer risk factors in MGEN women. Description of protocol, main characteristics and population].

This paper describes the design of E3N, a prospective cohort study on risk factors for female cancers, conducted in France. The cohort includes 100,000 women, aged 40 to 65 years at baseline in 1990. Participants were asked to complete questionnaires every 18 months. The main hypotheses studied concern the relationships between diet and cancer and between hormonal treatments and cancer. All cancer sites are registered together with other diseases (cardiovascular diseases, diabetes, osteoporosis). The follow-up procedure and the study population are described.

Adult↗

[Risk factors of allergopathy].

This review contains a detailed description of factors which determine the allergic danger in a region, the sources of allergens entering the environment, and classification of allergens according to their origin and ecological significance. The authors draw attention to the existing criteria of allergopathic conditions, which may serve as an important diagnostic index when establishing sensitization and performing specific diagnostics of allergic diseases. The article covers a complex of laboratory diagnostic methods, directed towards timely detection of allergopathology and its prevention.

Environmental Pollutants↗

Same patients, same critical events--different systems of care, different outcomes: description of a human factors approach aimed at improving the efficacy and safety of sedation/analgesia care.

The practice of sedating pediatric patients undergoing diagnostic and therapeutic procedures represents an ideal model for evaluating systems of health care delivery. We present detailed evidence of how different systems acting on the same patient under similar conditions result in very different outcomes. In contrast to epidemiological methods, our research follows a Human Factors approach of observing a small number of representative cases in great detail to characterize the critical components and processes of ideal sedation care. In this descriptive article we present a framework by which this work domain can be codified and evaluated. We conclude with a demonstration of how a patient simulator can be used to quantify responses to sedation emergencies. These data constitute the basis for innovating novel sedation care systems and strategies that will optimize safety and efficacy.

Analgesics↗

Heterogeneity of serum peptides with immunoactivity detected by a radioimmunoassay for proinsulin-like growth factor-II E domain: description of a free E domain peptide in serum.

We have reported that normal human sera contain immunoactivity (IA) detected by a RIA directed against the first 21 amino acids of the E domain of proinsulin-like growth factor-II (pro-IGF-II). Marked elevations of E-21 IA were found in the serum of patients with nonislet cell hypoglycemia (NICTH) and patients with renal failure receiving chronic hemodialysis. In this paper we describe some of the properties of the E-21 IA of normal and abnormal sera. The E-21 IA eluted from a calibrated acid Sephadex G-50 column as two major peaks. In normal serum the first major peak had a mol wt (Mr) between 14,000-15,000, and the second peak had a Mr between 5,000-6,000. When E-21 IA from serum of a patient with NICTH was similarly studied, most of the IA was present as a Mr 11,000 peak and only a small amount was present as a 5,000-6,000 Mr peak. In contrast, most of the E-21 IA present in the sera of patients on hemodialysis was present in the smaller molecular form, which eluted from a reverse phase column as a single component. This small Mr peak lacked determinants for the IGF-II monoclonal antibody (Amano), for pooled serum IGF-binding proteins, and for the IGF-I receptors on human placental membranes. We suggest that the 15- and 11-kilodalton peaks represent the glycated and unglycated forms of pro-IGF-II (E-21) reported by others. The glycated form appears to predominate in normal serum, whereas the nonglycated form predominates in the serum of patients with NICTH and renal failure. The 5,000-6,000 Mr E-21 IA probably represents a fragment of the free E domain of pro-IGF-II. Its size is consistent with cleavage of the free E domain between Arg46 and Arg47. The accumulation of this E-21 IA in renal failure is evidence that the kidney has a major role in the clearance of this fragment, which is not accomplished by the membranes used in hemodialysis.

Aged↗

Quality factor concept in piezoceramic transformer performance description.

A new general approach based on the quality factor concept to piezoceramic transformer (PT) performance description is proposed. The system's quality factor, material elastic anisotropy, and coupling factors of the input and output sections of an electrically excited and electrically loaded PT fully characterize its resonance and near-resonance behavior. The PT efficiency, transformation ratio, and input and output power were analytically analyzed and simulated as functions of the load and frequency for the simplest classical Langevin-type and Rosen-type PT designs. A new formulation of the electrical input impedance allows one to separate the power consumed by PT from the power transferred into the load. The system's PT quality factor takes into account losses in each PT "input-output-load" functional components. The loading process is changing PT input electrical impedance on the way that under loading the minimum series impedance is increasing and the maximum parallel impedance is decreasing coincidentally. The quality-factors ratio, between the states of fully loaded and nonloaded PT, is one of the best measures of PTs dynamic performance--practically, the lower the ratio is, the better PT efficiency. A simple and effective method for the loaded PT quality factor determination is proposed. As was found, a piezoceramic with low piezoelectric anisotropy is required to provide maximum PT efficiency and higher corresponding voltage gain. Limitations on the PT output voltage and power, caused by nonlinear effects in piezoceramics, were established.

Ceramics↗

Internalization of nerve growth factor by PC12 cells. A description of cellular pools.

Binding and internalization of nerve growth factor (NGF) by responsive cells is a complex process. We have incubated rat pheochromocytoma cells (PC12) with 125I-NGF at 37 degrees C and measured the association of ligand after removal of subsets of bound ligand by different methods. Chase with unlabeled NGF at either 4 or 37 degrees C, acid stripping, nonionic detergent stability, and combinations of these protocols were utilized. These variations of the binding assay were able to distinguish ligand bound to fast versus slow cell surface receptors, NGF bound to slow receptors at the cell surface versus cell interior, and soluble ligand versus cytoskeletally attached NGF. Quantitative and temporal relations among five cellular pools were defined. Experiments with the inhibitors chloroquine, cytochalasin B, and colchicine defined pools of NGF in terms of the route through the cell from the plasma membrane to the lysosome. Chloroquine caused accumulation of NGF only in the pool that was not associated with the cytoskeleton, implicating the involvement of this pool in supplying ligand to the lysosome. Results with cytochalasin B and colchicine suggest that both microfilaments and microtubules are involved in pathways leading to NGF degradation. A semiquantitative model for the movement of NGF through the cell is presented based on these observations.

Adrenal Gland Neoplasms↗

[Comparative analysis via data mining on the clinical features of Western medicine and Chinese medicine in diagnosing rheumatoid arthritis].

OBJECTIVE: To compare the clinical characteristics of traditional Chinese medicine (TCM) and Western medicine (WM) in diagnosing rheumatoid arthritis (RA). METHODS: A total of 85 clinical RA related messages were enacted and classified into 5 sets as pathological locations, quantitative diagnosis, symptomatic descriptions, general status and environment factors. The respective frequency of their presence in the TCM or WM data sets for RA diagnosis collected from MEDLINE and China National Knowledge Infrastructure (CNKI) were analyzed statistically by Chi-square test, and the relationship of some TCM diagnostic factors/conditions with the RA related biological factors was analyzed by co-occurrence-based literature approach of mining. RESULTS: There was significant difference between the diagnostic pattern of WM and TCM (P < 0.01). Compared with that of WM, TCM diagnosis on RA paid more attention to environmental factors and symptomatic descriptions, which showed definite association with the cytokines and neuro-endocrine factors in RA. CONCLUSION: Examination of environmental factors and symptomatic descriptions for RA diagnosis is one of the important characteristics of TCM treatment in accordance to syndrome differentiation, it has its potential biologic basis. A novel approach is proposed for exploring the characteristics of TCM in diagnosis and observation.

Arthritis, Rheumatoid↗

Factors determining the reliable description of global tumbling parameters in solution NMR.

An accurate description of global tumbling of a protein is essential for correct analysis and interpretation of internal dynamics and thermodynamics. The accurate fitting of global tumbling parameters is affected by the number of experimental relaxation data points available for analysis, the distribution of data points over the domain of the function describing the tumbling, the measurement error associated with the data, the error associated with use of an approximate functional form, and errors in the protein structure. We present an analysis of the influence of these factors on the error in global tumbling parameters and the corresponding error in the calculated T(1)/T(2) values. We find that reduction of experimental and approximation error can compensate for a less-than-ideal quantity or distribution of data points, and that accurate parameters can be obtained for proteins with highly anisotropic distributions of bond vectors, as illustrated using the helical bundle protein G-CSF. This indicates that proteins with anisotropic distributions, such as the helical bundle class of proteins, should not summarily be excluded when selecting proteins for dynamic and thermodynamic analyses of (15)N backbone relaxation measurements.

Anisotropy↗