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PubMedDate not supplied

A naturalistic test of Peplau's theory in home visiting.

Nurse-client relationships have been considered the foundation of successful home-visiting programs for vulnerable families. Even though nurse-client relationships are important when working with multiproblem families, relationship theory has not been used to guide interventions in home visiting. Identification of a fitting theory could provide direction for tailoring interventions to families at a "dose" individualized to meet their needs. This article reports a small study that tested the applicability of Peplau's theory of interpersonal relations in nursing (Peplau, 1952/1991) in the context of home visiting. Five prenatal clients and public health nurses participated in the study. Home visits were observed and audio-recorded beginning with the first prenatal home visit and ending in the early postpartum period. Audiotapes were transcribed and analyzed using a start list of codes based on Peplau's theory. Changes in the percentage of interaction assigned to the relationship phases along with a rating from the Relationship Form were compared over time to determine whether relationships progressed as predicted by Peplau. Findings of this study supported Peplau's theory. Implications for nursing practice and research are discussed.

House Calls↗
PubMed1987

Colour-coded stereo images from the tandem scanning reflected light microscope (TSRLM).

A method is described for the production of stereo-pair images in the tandem scanning reflected light microscope in which depths within the field imaged are coded in colour. The two images are recorded photographically whilst focusing vertically through the layer which is to be imaged. A horizontal component of motion is applied at the same time, but in opposing senses for the two images. Colour coding for depth is obtained by changing colour filters so that reflective features lying within different depth bands are imaged in corresponding colours.

Animals↗
PubMed1992

A mutant of human insulin-like growth factor II (IGF II) with the processing sites of proinsulin. Expression and binding studies of processed IGF II.

A mutant of human insulin-like growth factor II (IGF II) was constructed by site-directed mutagenesis: the nucleotides coding for Ser33 and Ser39 were changed to yield Arg and Lys, respectively, thus creating two pairs of basic residues, Arg-Arg and Lys-Arg, as flanking sequences of the remaining C domain. [Arg33, Lys39]IGF II was expressed in NIH-3T3 cells as a processed two-chain peptide with a deletion of amino acid residues 37-40 and crosslinked by three disulfide bonds. This des(37-40)[Arg33]IGF II showed 3.6-fold and 7.4-fold reduced affinities to the type 1 and type 2 IGF receptor overexpressing cells, respectively, whereas the thymidine incorporation potency was the same as that of wild-type IGF II. We speculate that the discrepancy between the reduced binding to the type 1 IGF receptor and the full thymidine incorporation potency is due to the 6.1-fold reduced affinity of the expressed mutant to the co-expressed IGF binding protein 3 (IGFBP-3). The results suggest that des(37-40)[Arg33]IGF II assumes a conformation very similar to IGF II, and that the entire length of the C domain is not essential for biological activity.

3T3 Cells↗
PubMed2004

Distribution and inheritance of beta-amylase alleles in north European barley varieties.

Allelic diversity and inheritance of polymorphic sites of the intron III-exon IV region of the seed specific beta-amylase gene Bmy1 were studied in a set of 55 barley accessions composed mainly of old Latvian and Scandinavian commercial varieties and three Hordeum spontaneum lines from Israel. A CAPS-marker was used for genotyping the C698 --> T polymorphism encoding alleles of beta-amylase with different thermostability. The genotype C698 which is diagnostic for a more thermostable isoform of the beta-amylase was detected in 13 of the investigated accessions. In most cases the origin of the C698 genotype could be traced back to the old Danish variety Binder in the pedigree. However, this genotype was lost in later varieties originating from Binder. A 6+1 bp deletion event in intron III of the beta-amylase gene was in all cases linked to the presence of the C698 mutation, while the repeat number of a microsatellite in intron III had no correlation to the presence of the C698 mutation. Sequence analysis revealed a number of haplotypes within exon IV that did not result in amino acid changes due to the degenerated genetic code.

Alleles↗
PubMed1998

On compensator design for photon beam intensity-modulated conformal therapy.

Recently the compensator has been shown to be an in expensive and reliable dose delivery device for photon beam intensity-modulated radiation therapy (IMRT). The goal of IMRT compensator design is to produce an optimized primary fluence profile at the patient's surface obtained from the optimization procedure. In this paper some of the problems associated with IMRT compensator design, specifically the beam perturbations caused by the compensator, are discussed. A simple formula is derived to calculate the optimal compensator thickness profile from an optimized primary fluence profile. The change of characteristics of a 6 MV beam caused by the introduction of cerrobend compensators in the beam is investigated using OMEGA Monte Carlo codes. It is found that the compensator significantly changes the energy spectrum and the mean energy of the primary photons at the patient's surface. However, beam hardening does not have as significant an effect on the percent depth dose as it does on the energy spectrum. We conclude that in most situations the beam hardening effect can be ignored during compensator design and dose calculation. The influence of the compensator on the contaminant electron buildup dose is found to be small and independent of the compensator thickness of interest. Therefore, it can be ignored in the compensator design and included as a correction into the final dose distribution. The scattered photons from the compensator are found to have no effect on the surface dose. These photons produce a uniform low fluence distribution at the patient's surface, which is independent of compensator shape. This is also true for very large fields and extremely asymmetric and nonuniform compensator thickness profiles. Compared to the primary photons, the scattered photons have much larger angular spread and similar energy spectrum at the patient's surface. These characteristics allow the compensator thickness profile and the dose distribution to be calculated from the optimized fluence profile of primary photons, without considering the scattered photons.

Calibration↗
PubMed1985

Normal expression of polymorphic endogenous retroviral RNA containing segments identical to mink cell focus-forming virus.

In the absence of infectious virus, strains of mice express polyadenylated RNA transcripts homologous to the genome of murine leukemia virus. In addition to transcripts consistent with full-length and spliced env retroviral RNAs, several unique RNA species which lack the env sequence accumulate in a tissue-specific manner. These RNA species are presumed to be transcribed from endogenous retroviral sequences that constitute the bulk of the murine leukemia virus-related sequences in the murine genome. To determine the relationship of these RNA transcripts to infectious murine leukemia virus and the precise structural basis of the heterogeneity observed for the env-lacking transcripts, we isolated and sequenced cDNA recombinants representing the RNAs expressed in strain 129 GIX+ mice. Comparisons of the nucleotide sequences demonstrated that the endogenous retroviral transcripts differed in pol, p15E, and R-peptide regions by single nucleotide changes. In contrast, the gp70-coding regions of two cDNA clones derived from epididymis and liver were completely homologous over a 599-nucleotide overlapping sequence. The structures of env-lacking transcripts were examined in two independent cDNA clones, and each was found to contain a different deletion that was potentially mediated by seven-base pair direct repeats in the intact sequence. The extensive sequence homology between cDNAs allowed construction of a cumulative sequence map of the 3' end of an intact endogenous retroviral transcript. A comparison of this sequence with infectious ecotropic and mink cell focus-forming viruses revealed that the endogenous transcripts are highly homologous with the substituted portions of leukemogenic mink cell focus-forming viruses and therefore further define the boundaries of recombination required to generate these viruses.

Amino Acid Sequence↗
PubMed2005

Rearrangement of simian virus 40 regulatory region is not required for induction of progressive multifocal leukoencephalopathy in immunosuppressed rhesus monkeys.

Rearrangements of the JC virus (JCV) regulatory region (RR) are consistently found in the brains of patients with progressive multifocal leukoencephalopathy (PML), whereas the archetype RR is present in their kidneys. In addition, the C terminus of the large T antigen (T-Ag) shows greater variability in PML than does the rest of the coding region. To determine whether similar changes in simian virus 40 (SV40) are necessary for disease induction in monkeys, we sequenced the SV40 RR and the C terminus of the T-Ag from the brain of simian/human immunodeficiency virus (SHIV)-infected monkey 18429, which presented spontaneously with an SV40-associated PML-like disease, as well as from the peripheral blood mononuclear cells (PBMC), kidneys, and brains of SV40-seronegative, SHIV-infected monkeys 21289 and 21306, which were inoculated with the 18429 brain SV40 isolate. These animals developed both SV40-associated PML and meningoencephalitis. Thirteen types of SV40 RR were characterized. Compared to the SV40 archetype, we identified RRs with variable deletions in either the origin of replication, the 21-bp repeat elements, or the late promoter, as well as deletions or duplications of the 72-bp enhancer. The archetype was the most prominent RR in the brain of monkey 18429. Shortly after inoculation, a wide range of RRs could be found in the PBMC of monkeys 21289 and 21306. However, the archetype RR became the predominant type in their blood, kidneys, and brains at the time of sacrifice. On the contrary, the T-Ag C termini remained identical in all compartments of the three animals. These results indicate that unlike JCV in humans, rearrangements of SV40 RR are not required for brain disease induction in immunosuppressed monkeys.

Amino Acid Sequence↗
PubMed1980

Ischaemic heart disease in young hypertensive women.

The association between hypertension and ischaemic heart disease was explored in a retrospective analysis of 50 severely hypertensive premenopausal women (presenting diatolic pressure greater than or equal to 120 mmHg) under 45 years of age who were seen over a seven-year period. Twenty-two per cent of these patients had angina pectoris, and 38 per cent had Minnesota code 4-1 or 5-1 changes on the resting electrocardiogram. The contribution of other risk factors, including smoking habits, was assessed: 72 per cent of the patients smoked; significantly less smoking was found among two groups of age-matched women with less severe hypertension [diastolic pressures of 90 to 104 mmHg (n=50) and 105 to 119 mmHg (n=50)]. In these latter groups, only one patient had angina pectoris and none had 4-1 or 5-1 changes on the electrocardiogram.

Adult↗
PubMed1998

Novel TIGR/MYOC mutations in families with juvenile onset primary open angle glaucoma.

Mutations in the trabecular meshwork induced glucocorticoid response protein (TIGR) or myocilin (MYOC) has recently been shown to cause juvenile onset primary open angle glaucoma (JOAG). In this study, we identified two new mutations (Asp380Ala and Ser502Pro) in two British families and another (Pro370Leu) in a French-Canadian family. These mutations were not present in a total of 106 normal chromosomes. In another Turkish family with JOAG, we also detected a sequence variant that was proven to be an amino acid polymorphism (Arg76Lys). No other sequence changes were found in the entire coding region and splice junctions of the TIGR/MYOC gene in this family. However, it is still possible that mutations either in the TIGR promoter or in another neighbouring gene could cause glaucoma in this JOAG family. Our results confirm the role of the TIGR/MYOC gene in the aetiology of the JOAG phenotype.

Adolescent↗
PubMed2006

Predicting the effects of amino acid substitutions on protein function.

Nonsynonymous single nucleotide polymorphisms (nsSNPs) are coding variants that introduce amino acid changes in their corresponding proteins. Because nsSNPs can affect protein function, they are believed to have the largest impact on human health compared with SNPs in other regions of the genome. Therefore, it is important to distinguish those nsSNPs that affect protein function from those that are functionally neutral. Here we provide an overview of amino acid substitution (AAS) prediction methods, which use sequence and/or structure to predict the effect of an AAS on protein function. Most methods predict approximately 25-30% of human nsSNPs to negatively affect protein function, and such nsSNPs tend to be rare in the population. We discuss the utility of AAS prediction methods for Mendelian and complex diseases as well as their broader applications for understanding protein function.

Amino Acid Sequence↗
PubMed1992

Gonadotropin and cAMP modulation of IGE binding protein production in ovarian granulosa cells.

Porcine granulosa cells (GC) produce insulin-like growth factor (IGF) binding protein (BP)-3 and IGFBP-2 in culture. A gonadotropin, follicle-stimulating hormone (FSH), dramatically inhibited GC production of these IGFBPs in control cultures and in cultures stimulated by insulin plus epidermal growth factor (EGF) or IGF-I plus EGF. Stimulators of adenylate cyclase (forskolin, cholera toxin) and a derivative of adenosine 3',5'-cyclic monophosphate (cAMP), 8-bromoadenosine 3',5'-cyclic monophosphate, inhibited IGFBP synthesis in a manner similar to FSH. In contrast, the antagonist of cAMP action, (R)-p-adenosine 3',5'-cyclic phosphorothioate [(R)-p-cAMPS], significantly stimulated production of IGFBP-3 and IGFBP-2 compared with controls. This stimulatory effect of (R)-p-cAMPS was counteracted by cotreatment with FSH in a dose-dependent manner. Finally, treatment of GC cultures with FSH plus 3-isobutyl-1-methylxanthine resulted in a significant reduction in cellular content of mRNA coding for IGFBP-3 with no change in IGFBP-2 mRNA. In summary, agents that elevate intracellular cAMP were found to mimic the effects of FSH on IGFBP production.

Animals↗
PubMed2006

Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r).

Quantitative trait loci (QTL) for carbohydrate (Mnic1) and total energy (Kcal2) intake on proximal mouse chromosome 17 were identified previously from a C57BL/6J (B6) X CAST/Ei (CAST) intercross. Here we report that a new congenic strain developed in our laboratory has confirmed this complex locus by recapitulating the original linked phenotypes: B6.CAST-17 homozygous congenic mice consumed more carbohydrate (27%) and total energy (17%) compared with littermate wild-type mice. Positional gene candidates with relevance to carbohydrate metabolism, glyoxalase I (Glo1) and glucagon-like peptide-1 receptor (Glp1r), were evaluated. Glo1 expression was upregulated in liver and hypothalamus of congenic mice when compared with B6 mice. Analyses of Glp1r mRNA and protein expression revealed tissue-specific strain differences in pancreas (congenic>B6) and stomach (B6>congenic). These results suggest the possibility of separate mechanisms for enhanced insulin synthesis and gastric accommodation in the presence of high carbohydrate intake and larger food volume, respectively. Sequence analysis of Glp1r found a G insert at nt position 1349, which results in earlier termination of the open reading frame, thus revealing an error in the public sequence. Consequently, the predicted length of GLP-1R is 463 aa compared with 489 aa, as previously reported. Also, we found a polymorphism in Glp1r between parental strains that alters the amino acid sequence. Variation in Glp1r could influence nutrient intake in this model through changes in the regulatory or protein coding regions of the gene. These congenic mice offer a powerful tool for investigating gene interactions in the control of food intake.

Animals↗
PubMed2026

Oncogenic SF3B1 mutations alter the splicing of mRNA noncoding regions to induce a novel therapeutic vulnerability.

Oncogenic mutations of SF3B1 are common in myeloid cancers, chronic lymphocytic leukemia (CLL), and select solid tumors. Their mechanistic basis for promoting oncogenesis has been investigated in detail, with the stereotyped missplicing of messenger RNA (mRNA) protein coding sequences most intensively studied. These changes, in genes such as MAP3K7, BRD9, and ABCB7, typically lead to loss of function, thus contributing to cancer pathogenesis. Here, we systematically analyzed the impact of mutant SF3B1 on noncoding regions of mRNA transcripts across disease types, in both cell lines and primary patient specimens. This identified numerous novel and highly reproducible splicing alterations in such regions. Studies of a target gene, DCAF16, revealed multiple complex mutation-induced alterations in its 5' and 3' untranslated regions (UTRs). Remarkably, these were mechanistically associated with increased DCAF16 protein levels in SF3B1-mutant cells, representing, to our knowledge, the first time that oncogenic SF3B1 has been found to increase levels of a target protein in a gain-of-function manner. DCAF16 is a substrate recognition adapter for the DDB1/CUL4 E3 ubiquitin ligase complex. Novel protein degrader small molecules that coopt DCAF16 to degrade BRD4 as a neosubstrate demonstrated preferential selectivity for SF3B1-mutant cancers and CLL primary patient specimens due to increased DCAF16 protein levels. In turn, this reveals the therapeutic relevance of mutant SF3B1 dysregulation of transcript UTRs and uncovers a novel strategy for the treatment of these important neoplasms.

Humans↗
PubMed1999

A novel nonsense mutation in CACNA1A causes episodic ataxia and hemiplegia.

OBJECTIVE: To identify the disease-causing mutation and to characterize penetrance and phenotypic variability in a large pedigree with episodic ataxia type 2 (EA-2) previously linked to chromosome 19. BACKGROUND: Mutations in the CACNA1A gene on chromosome 19 encoding a calcium channel subunit cause EA-2, which is characterized by recurrent attacks of imbalance with interictal eye movement abnormalities. METHODS: The authors used single-strand conformation polymorphism (SSCP) analysis to screen for point mutations, and direct sequencing to identify mutations in CACNA1A. Allele-specific oligonucleotides were designed to detect the presence of the diseased allele in members of their pedigree as well as in normal control subjects. RESULTS: Reassessment of members of the pedigree revealed two notable clinical features. Diffuse weakness during attacks of ataxia was a prominent complaint. Two affected individuals had had episodic hemiplegia, one with typical migraine headaches. SSCP analysis revealed aberrant bands in exon 29 in affected members but not in normal control subjects. Direct sequencing of exon 29 identified a C-to-T change at position 4914 of the coding sequence of CACNA1A, predicting an early stop code at codon 1547. Two asymptomatic mutation carriers demonstrated the incomplete penetrance of this mutation. CONCLUSIONS: A nonsense mutation in CACNA1A causes episodic ataxia and complaint of weakness, and may be associated with hemiplegia.

Adolescent↗
PubMed1999

Pharmacy practice acts: a decade of progress.

OBJECTIVE: This 10-year follow-up study of previously published surveys of pharmacy practice acts examines 50 state and the District of Columbia pharmacy practice acts to assess the range of statutory definitions and determine the direction and magnitude of statutory changes since 1988. DATA SOURCES: State codes for 50 states and the District of Columbia, with attention focused on the pharmacy practice acts; Puerto Rico and the Virgin Islands were excluded. DATA EXTRACTION: The focus on each statute was the statutory definition of the "practice of pharmacy." DATA SYNTHESIS: Comparing 1998 with 1988, codification of interpreting and evaluating prescriptions increased 22% (1998; 39/47, four states contain no definition of the practice of pharmacy), compounding 8% (47/47), consultation 19% (41/47), dispensing 2.5% (47/47), drug administration threefold (24/47), drug product selection twofold (45/47), drug utilization review 70% (35/47), patient assessment 6.5-fold (6/47), pharmacokinetic services threefold (3/47), pharmacist prescribing 4.6-fold (15/47), and participation in drug research 10.5-fold (10/47). CONCLUSIONS: Since 1988, state pharmacy practice acts have increased the codification of pharmaceutical care services as integral pharmacy functions. Although substantial progress has been made over the past decade, a number of states have not incorporated definitions of pharmaceutical care functions into their state statutes. Enactment of the National Association Boards of Pharmacy Model State Pharmacy Act is one way for pharmacists' practice to expand with the evolution of the practice of pharmacy.

Humans↗
PubMed2005

Protein-mediated surface structuring in biomembranes.

The lipids and proteins of biomembranes exhibit highly dissimilar conformations, geometrical shapes, amphipathicity, and thermodynamic properties which constrain their two-dimensional molecular packing, electrostatics, and interaction preferences. This causes inevitable development of large local tensions that frequently relax into phase or compositional immiscibility along lateral and transverse planes of the membrane. On the other hand, these effects constitute the very codes that mediate molecular and structural changes determining and controlling the possibilities for enzymatic activity, apposition and recombination in biomembranes. The presence of proteins constitutes a major perturbing factor for the membrane sculpturing both in terms of its surface topography and dynamics. We will focus on some results from our group within this context and summarize some recent evidence for the active involvement of extrinsic (myelin basic protein), integral (Folch-Lees proteolipid protein) and amphitropic (c-Fos and c-Jun) proteins, as well as a membrane-active amphitropic phosphohydrolytic enzyme (neutral sphingomyelinase), in the process of lateral segregation and dynamics of phase domains, sculpturing of the surface topography, and the bi-directional modulation of the membrane biochemical reactivity.

Humans↗
PubMed1992

Establishing therapeutic alliance across cultural barriers.

1. The therapeutic alliance is a mutually defined helping relationship that encompasses mutual respect and acceptance of ethnocultural variance, predicated upon empathic rapport. 2. Sensitivity to two psycholinguistic phenomena may help establish a transcultural relationship: the detachment effect (limited expression of affect and reduced access to developmental events between languages) and code switching (a complete or partial change of language or dialect within a single utterance or conversation). 3. Issues related to differing sociocultural expectations of nurses and clients will be increasingly encountered as ease of travel combines with economic and political unrest to produce increasing numbers of displaced persons.

Attitude to Health↗
PubMed2004

Mammography screening in Switzerland: limited evidence from limited data.

QUESTIONS UNDER STUDY: In Switzerland controversy exists on how to summarise the evidence on the efficacy and effectiveness, as well as adverse effects, of mammography screening, and breast cancer mortality trends are often discussed in the context of the impact of mammography. PRINCIPLES/METHODS: Single-study publications, meta-analyses, and reports by international expert groups on mammography screening are reviewed. Breast cancer mortality trends from 1970-2000 are reported and discussed in the context of the Swiss screening situation. RESULTS: In Switzerland breast cancer mortality rates for female Swiss nationals aged 50-79 years fell between 1990 and 2000 by some 25% in all language regions. The data from randomised studies in large populations in several countries with well organised mammography programmes prompt the conclusion that participation in organised screening programmes with rigorous quality standards reduces breast cancer mortality. The achievable long-term reduction in breast cancer mortality ranges from 5-20% in the target population provided that appropriate diagnostic investigation and treatment are available. To achieve this in Switzerland 830 to 3300 women need to be invited to screening for ten years to prevent one death from breast cancer. The risk-benefit profile of mammography screening is likely to be less favourable if mammographies are performed outside the context of organised screening programmes. In Switzerland we are now confronted with growing regional disparities in access to screening mammography which is under systematic quality control. CONCLUSIONS: The decrease in breast cancer mortality in Switzerland is most probably due to treatment developments and changes in cause-of-death coding. Public health measures in Switzerland should aim at regulating quality control for screening mammography, monitoring mammography use and improving the information on mammography available to women. For an evidence-based decision regarding health insurance coverage of screening mammography in 2007, large gaps need to be filled. The current coexistence of systematic screening programmes and opportunistic screening, with distinct regional differences, provides a unique opportunity for research into the merits and drawbacks of the two approaches.

Aged↗