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Biomedical subjects

E Fisher

Publications and source records attributed to E Fisher.

At least 55 records · Page 3Linked to original sources
PubMed1998

Apolipoprotein E2 (Arg136 --> Cys) mutation in the receptor binding domain of apoE is not associated with dominant type III hyperlipoproteinemia.

Using apoE phenotyping by immunoblotting and apoE genotyping we identified four heterozygous carriers of a rare apolipoprotein (apo) E2 variant, apoE2 (Arg136 --> Cys). ApoE2 (Arg136 --> Cys) was not distinct from apoE2 (Arg158 --> Cys) by phenotyping, but produced a unique pattern of bands on CfoI restriction typing of a 244 bp apoE gene fragment. Two of the four apoE2 (Arg136 --> Cys)/3 heterozygotes had elevated triglycerides, two were normolipidemic. The composition of very low density lipoproteins (VLDL) was normal in each of the four apoE2 (Arg136 --> Cys) carriers, regardless of the triglyceride concentrations. None of the apoE2 (Arg136 --> Cys) carriers displayed a broad beta-band and none revealed beta-migrating particles in the VLDL. The two hypertriglyceridemic carriers of apoE2 (Arg136 --> Cys) were, therefore, classified as having type IV rather than type III hyperlipoproteinemia. LDL receptor binding activities were studied using recombinant apoE loaded to dimyristoylphosphatidylcholine (DMPC) vesicles and to VLDL and from an apoE-deficient individual. LDL receptor binding of apoE2 (Arg136 --> Cys) was 14% of apoE3 and was thus higher than that of apoE2 (Arg158 --> Cys). Both apoE2 (Arg136 --> Cys) and apoE2 (Arg158 --> Cys) displayed substantial heparin binding (61 and 53% of apoE3, respectively). As the dominant apoE variants known so far are characterized by more pronounced reductions of heparin binding, we suggest that apoE2 (Arg136 --> Cys) is not associated with dominant expression of type III hyperlipoproteinemia. These findings lend support to the concept that apoE variants predisposing to dominant type III hyperlipoproteinemia differ from recessive mutations by a more severe defect in heparin binding.

Adult↗
PubMed1997

A survey of women with HIV about their expectations for care.

As an increasing number of women become infected with the human immunodeficiency virus (HIV), it is important to understand their expectations regarding the health care services they receive. In 1995 a new centre was opened at an academic centre in St Louis, Missouri, to provide comprehensive care to women with HIV. To assist in the Centre's development, we interviewed 50 of 119 enrolled clients (42%) using a survey instrument focusing on what they consider important in their care. In response to open-ended questions, clients most often mentioned wanting a sense of personalized caring and respect by medical staff (n = 28, [56%]), having someone to talk to about problems (n = 28, [56%]), honest answers about their condition (n = 23, [46%]), medical follow-up (n = 21, [42%]), reduced barriers to care (n = 20, [40%]), and education about their condition (n = 15, [30%]). The highest-ranked aspects of care were seeing the doctor, learning about their condition, and being seen in a pleasant environment (92% [n = 46%]). Significant differences were found in some responses when analysed according to race, educational level, and severity of disease. It is important that programmes delivering health care services to women with HIV provide services that take into account their individualized needs. Ideally, this requires incorporation of a multidisciplinary team to provide psychological and social support, patient education, and medical management.

Adult↗
PubMed1997

Identification of an oligodeoxynucleotide sequence motif that specifically inhibits phosphorylation by protein tyrosine kinases.

Protein tyrosine kinases (PTKs) have central roles in cellular signal transduction. We have identified a sequence motif (CGT[C]GA) in phosphorothioate-modified oligodeoxynucleotides (ODNs) that specifically inhibits the enzymatic activity of recombinant or immunoprecipitated PTK in vitro. Hexamer ODNs containing this motif block both substrate and autophosphorylation of at least four different PTKs but have no apparent effect on the enzymatic activity of a serine/threonine protein kinase. These data suggest possible new applications for ODNs and have implications for the design and interpretation of experiments using antisense or triplex ODNs.

Cell Line↗
PubMed1997

The case of Powhatan Correctional Center/Virginia Department of Corrections and Virginia Commonwealth University/Medical College of Virginia.

OBJECTIVE: To implement a cost/benefit analysis of telemedicine subspecialty care provided between the Powhatan Correctional Center (PCC) of the Virginia Department of Corrections (Corrections) and the Medical College of Virginia campus of Virginia Commonwealth University (MCV/VCU). METHODS: We evaluated the costs and benefits of the implementation of telemedicine for HIV-positive inmates. Benefits included dollar savings in transportation and medical reimbursement. Costs included those of operating the telemedicine system and of medical care. Non-dollar benefits included implementing more consistent and timely treatment of inmates and reducing security risk. RESULTS: Over the 7-month study period, the total number of HIV consults by telemedicine was 165. The Department of Corrections was able to achieve transportation and medical savings of $35,640 and $21,123, respectively. The operating costs for the telemedicine services totaled $42,277. The net benefit, which is the difference between cost savings and total operating costs, was $14,486. CONCLUSION: Telemedicine increased access to care for HIV-positive inmates and generated cost savings in transportation and care delivery.

Cost Savings↗
PubMed1997

Histopathologic and biochemical changes in the muscles affected by distraction osteogenesis of the mandible.

Lengthening of the canine mandible using an intraoral distraction device was performed in order to study the effects of distraction on the associated muscles of mastication. Biopsies of the masseter and digastric muscles were taken after lengthening at four different time intervals to assess the temporal changes in the masticatory muscles of 10 dogs. Biopsies of the muscles on the contralateral side also were taken from 6 of these dogs before lengthening to establish a control group. Each biopsy was analyzed histologically and spectophotomerically for RNA, DNA and protein content. The digastric muscle underwent transient atrophy with initiation of distraction but regenerated completely after 48 days of fixation. The masseter muscle was unchanged initially but showed evidence of atrophy only after 20 mm of distraction it continued to exhibit evidence of atrophy during fixation. Protein synthesis was decreased significantly during periods of atrophy in the masseter; no such change was noted in the digastric. Unlike the masseter, the digastric fibers lie in a plane parallel to the vector of distraction. These findings suggest that any muscle affected by skeletal distraction in the same plane or vector (e.g., digastric) adapts with compensatory regeneration and hypertrophy. Moreover, those muscles lying in a different plane (e.g., masseter) show persistent evidence of atrophy with decreased protein synthesis.

Animals↗
PubMed1997

The distance to community medical care and the likelihood of hospitalization: is closer always better?

OBJECTIVES: This study examined the influence that distance from residence to the nearest hospital had on the likelihood of hospitalization and mortality. METHODS: Hospitalizations were studied for Maine. New Hampshire, and Vermont during 1989 (adults) and for 1985 through 1989 (children) and for mortality (1989) in Medicare enrollees. RESULTS: After other known predictors of hospitalization (age, sex, bed supply, median household income, rural residence, academic medical center, and presence of nursing home patients) were controlled for, the adjusted rate ratio of medical hospitalization for residents living more than 30 minutes away was 0.85 (95% confidence interval [CI] = 0.82, 0.88) for adults and 0.78 (95% CI = 0.74, 0.81) for children, compared with those living in a zip code with a hospital. Similar effects were seen for the four most common diagnosis-related groups for both adults and children. The likelihood of hospitalization for conditions usually requiring hospitalization and for mortality in the elderly did not differ by distance. CONCLUSIONS: Distance to the hospital exerts an important influence on hospitalization rates that is unlikely to be explained by illness rates.

Adolescent↗
PubMed1996

Health of the public: The private-sector challenge.

The rapid growth of managed care poses challenges and opportunities for the health of the public. The fundamental risk is that both mission and accountability will be defined too narrowly; the opportunity lies in broadening both. What would a socially responsible managed care system look like? Such a system would provide excellent individual care to its enrollees, yet it would also include programs and activities that address broader populations and policies. We propose 8 attributes of such a system that can be used as a guide by managed care systems and to judge whether a managed care system is a responsible, accountable, and responsive contributor to the health of its community. As the role of the public sector shrinks, the private sector must expand its responsibility. It is both prudent and reasonable for managed care systems to seize their unique opportunity to improve the health of the public.

Delivery of Health Care↗
PubMed1996

Oligonucleotide uptake in human hematopoietic cells is increased in leukemia and is related to cellular activation.

The use of antisense oligonucleotides as tools for modulating gene expression represents a novel strategy for designing drugs to treat a variety of diseases. Several factors, including cellular uptake and internalization of the oligonucleotides, are important parameters in determining the effectiveness of antisense agents such as therapeutic drugs. We have studied oligonucleotides uptake in normal and leukemic human hematopoietic cells, such as peripheral blood, bone marrow (BM), and HL-60 cell line; and have found that, in normal human blood and BM, myeloid cells and B cells preferably took up more oligonucleotides than T cells. There was no marked difference in oligonucleotide uptake between CD4+ helper T cells and CD8+ cytolytic T cells. Leukemic cells had greater oligonucleotide uptake than their normal counterparts. Furthermore, oligonucleotide uptake was closely related to cell activation status and can be modulated by growth factors or inhibitors. These studies provide a basis for using oligonucleotides as therapeutic drugs both in vitro and in vivo.

Base Sequence↗
PubMed1996

Evidence that a locus for familial psoriasis maps to chromosome 4q.

Psoriasis is an inflammatory skin disease that affects 2% of the population. It is characterised by red, scaly skin patches which are usually found on the scalp, elbows and knees, and may be associated with severe arthropathy. The lesions are caused by abnormal keratinocyte proliferation, and infiltration of inflammatory cells into the dermis and epidermis. The usual age of onset of psoriasis is between 15 and 30 years, although it can present at any age. Psoriasis is recognised to have a large genetic component. Twin studies show the concordance in monozygotic twins to be between 65-70%, compared to between 15-20% in dizygotic twins. Family studies estimate the risk to first degree relatives at between 8-23%. However, there are also several environmental factors, including streptococcal infection and stress, that affect the onset and presentation of the disease. The mode of inheritance of psoriasis is unclear. We conducted a genome-wide scan to search for psoriasis susceptibility loci in a single large multiplex family. Parametric linkage analysis indicated that a susceptibility locus for familial psoriasis was located on chromosome 4q. Investigation of this locus in five further multiplex families using both parametric and non-parametric methods gave significant localisation to chromosome 4q. The maximum total pairwise lod score obtained was 3.03 with the microsatellite marker D4S1535 at theta = 0.08. Non-parametric multipoint analysis with GENEHUNTER- demonstrated significant excess allele sharing, with a P value of 0.0026, at the same locus.

Chromosome Mapping↗
PubMed1996

Oligodeoxynucleotide modifications determine the magnitude of B cell stimulation by CpG motifs.

We have recently reported that oligodeoxynucleotides (ODN) that contain a CpG dinucleotide flanked by two purines on the 5'-side and two pyrimidines on the 3'-side induce potent B cell proliferation and differentiation. The present study investigates the role of the ODN backbone in determining the magnitude of the lymphocyte stimulation. Phosphorothioate ODN were approximately 2 logs more potent than the same sequence with a phosphodiester backbone. Chimeric ODN in which the 5'- and 3'-ends were modified with nuclease-resistant internucleotide linkages induced widely varying degrees of immune activation depending on the modification. Phosphorodithioate linkages were by far the most potent and induced B cell activation at nanomolar concentrations, approximately 1 log lower than required for the next most potent modification, phosphorothioate. Methylphosphorothioate terminal linkages were slightly more potent than phosphodiester, which were in turn slightly more potent than terminal methylphosphonate-modified ODN.

Animals↗
PubMed1996

Differential regulation of the leukotoxin operon in highly leukotoxic and minimally leukotoxic strains of Actinobacillus actinomycetemcomitans.

The expression of the leukotoxin (ltx) operon varies significantly among Actinobacillus actinomycetemcomitans strains. The dual promoters driving ltx expression in the highly toxic strain JP2 have been previously characterized (J. M. Brogan, E. T. Lally, K. Poulsen, M. Kilian, and D. R. Demuth, Infect. Immun. 62:501-508, 1994), and genetic analyses of A. actinomycetemcomitans suggest that highly toxic strains like JP2 arose from minimally toxic strains, presumably by deletion of a 530-bp domain within the ltx promoter region (K. Poulsen, E. Theilade, E.T. Lally, D. R. Demuth, and M. Kilian, Microbiology 140:2049-2060, 1994). However, the ltx promoter of minimally toxic A. actinomycetemcomitans strains has not been well characterized. In this study, deletion and primer extension analyses showed that the ltx promoter of A. actinomycetemcomitans 652 is situated approximately 150 bp upstream of the ltxC gene and initiates transcription 138 nucleotides upstream of ltxC. In contrast to strain JP2, only a single promoter appears to drive ltx expression in 652. The 652 promoter resides within the 530-bp region that is absent from the JP2 promoter sequence, suggesting that the specific sequences controlling ltx expression differ in highly toxic and minimally toxic A. actinomycetemcomitans strains. In addition, ltx expression in strain 652 was shown to be induced three- to fourfold when cells were grown under anaerobic conditions. The induction of whole cell leukotoxicity, was accompanied by increases in the levels of Ltx polypeptide and the steady-state levels of ltx mRNA, suggesting that regulation occurred at the level of transcription. In contrast, the levels of leukotoxicity, Ltx polypeptide, and fix mRNA in strain JP2 were unaffected by anaerobic growth. These results suggest that the ltx operon is differentially regulated in highly toxic and minimally toxic A. actinomycetemcomitans strains and that the sequences controlling the oxygen-dependent regulation of ltx expression may reside within the 530-bp domain that is not present in highly toxic A. actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans↗
PubMed1995

Chloride transport activation by plasma osmolarity during rapid adaptation to high salinity of Fundulus heteroclitus.

Transition from low salt water to sea water of the euryhaline fish, Fundulus heteroclitus, involves a rapid signal that induces salt secretion by the gill chloride cells. An increase of 65 mOsm in plasma osmolarity was found during the transition. The isolated, chloride-cell-rich opercular epithelium of sea-water-adapted Fundulus exposed to 50 mOsm mannitol on the basolateral side showed a 100% increase in chloride secretion, which was inhibited by bumetanide 10(-4) M and 10(-4) M DPC (N-Phenylanthranilic acid). No effect of these drugs was found on apical side exposure. A Na+/H+ exchanger, demonstrated by NH4Cl exposure, was inhibited by amiloride and its analogues and stimulated by IBMX, phorbol esters, and epithelial growth factor (EGF). Inhibition of the Na+/H+ exchanger blocks the chloride secretion increase due to basolateral hypertonicity. A Cl-/HCO3- exchanger was also found in the chloride cells, inhibited by 10(-4) M DIDS but not involved in the hyperosmotic response. Ca2+ concentration in the medium was critical for the stimulation of Cl- secretion to occur. Chloride cell volume shrinks in response to hypertonicity of the basolateral side in sea-water-adapted operculi; no effect was found on the apical side. Fresh-water-adapted fish chloride cells show increased water permeability of the apical side. It is concluded that the rapid signal for adaptation to higher salinities is an increased tonicity of the plasma that induces chloride cell shrinkage, increased chloride secretion with activation of the Na+K+2Cl- cotransporter, the Na+/H+ exchanger and opening of Cl- channels.

Adaptation, Physiological↗
PubMed1995

The Perception of Teasing Scale (POTS): a revision and extension of the Physical Appearance Related Teasing Scale (PARTS).

This article describes the development and validation of a revised measure for the assessment of history of being teased about physical appearance. Study 1 involved the preliminary psychometric evaluation of the questionnaire on a sample of 227 college women, Two factors emerged: Weight-Related Teasing (WT) and Teasing About Abilities/Competencies (Competency Teasing; CT). The integrity of the factor structure of these two scales was established in Study 2 with a sample of 87 college women. Internal consistency ratios in this sample were also found to be acceptable. In Study 3, 92 college women were administered measures of body image, eating disturbance, and self-esteem to test for convergence with the Perception of Teasing Scale. Subjects also rated teasing items for frequency and effect (e.g., how upset they were by the teasing). Two-week test-retest reliabilities for these measures were acceptable. Weight-Related Teasing correlated to a greater degree with other measures than Competency Teasing. Regression analyses revealed the importance of a frequency versus effect dimension. Findings are discussed in light of recent research on developmental factors in body image and eating disturbance.

Journal Article↗
PubMed1995

The effect of independent film and object rotation on projective geometric standardization of dental radiographs.

Digital alignment of dental X-ray images using projective invariants has been shown to be a feasible method for detecting changes through digital subtraction radiography. Previous research on the validity of the standardization procedure has considered the effects of motion of the X-ray source alone. Here the effects of independent motion of the film and the object on the standardization are investigated. This is accomplished by fitting a wire grid to the X-ray source, which allows for correction of film motion separately. The usefulness of separating the motion corrections is discussed, as well as some possible sources of error in the overall standardization procedure. The results of the standardization were found not to differ significantly whether the motions were corrected for separately or simultaneously.

Algorithms↗