Scrapie in immunodeficient mice.
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Animals↗
Biomedical subjects
K Stewart
Publications and source records attributed to K Stewart.
Transvaginal ultrasound measurement of endometrial thickness and endometrial pipelle sampling as an alternative diagnostic procedure to hysteroscopy and dilatation and curettage in the management of post-menopausal bleeding.
In order to evaluate pipelle endometrial sampling combined with ultrasound measurement of endometrial thickness as an initial diagnostic procedure in the assessment of endometrial pathology in patients presenting with postmenopausal bleeding, 50 consecutive patients were studied prospectively. In each patient measurement of endometrial thickness and pipelle endometrial biopsy were performed as an out-patient procedure before hysteroscopy and dilatation and curettage (D&C). The diagnostic sensitivity with pipelle endometrial sampling alone in detecting endometrial pathology was 25% with a specificity of 100%. The measurement of endometrial thickness had a sensitivity of 62% with a specificity of 87.8%. Pipelle sampling combined with endometrial thickness increased the sensitivity to 87.5% with a specificity of 87.8%. Therefore, we suggest that pipelle sampling combined with sonographic measurement of endometrial thickness is an acceptable, less invasive alternative to hysteroscopy and D&C as a first-line investigation in the management of post-menopausal bleeding.
Journal Article↗
Severely combined immunodeficient (SCID) mice resist infection with bovine spongiform encephalopathy.
Following combined intraperitoneal and intracerebral injection with bovine spongiform encephalopathy (BSE) cow brain homogenate, SCID mice show a resistance to infection in comparison with immunocompetent CB20 mice. BSE occurred in only five out of 22 challenged SCID mice, with a mean incubation period of 573 days, whereas all the CB20 mice developed the disease with a mean incubation period of 456 days. In contrast, previous studies have shown that intracerebral infection of SCID mice with a mouse-passaged scrapie strain, ME7, produces 100% incidence of disease but no replication of infectivity in spleen. The results with BSE suggest that there is little or no direct infection of the CNS in interspecies transmissions, but that processing or replication of infectivity in peripheral lymphoid tissues may facilitate subsequent spread of infection to the CNS.
Animals↗
Cell type-specific expression in brain cell cultures from a short human cytomegalovirus major immediate early promoter depends on whether it is inserted into herpesvirus or adenovirus vectors.
Expression from a short human cytomegalovirus (HCMV) major immediate early (IE) promoter-enhancer was tested in three different virus vectors: recombinant adenovirus (Ad), recombinant herpes simplex virus type 1 (HSV-1) and HSV-1-derived amplicon vectors. The HCMV major IE promoter-enhancer within a replication-deficient recombinant Ad vector was shown to produce cell-specific expression in rat nervous system cell cultures. Recombinant Ad entered all cell types examined but the HCMV major IE promoter was silent in primary cultures of neocortical neurons and Schwann cells, although it drove transgene expression in astrocytes and fibroblasts. Moreover, in neurons and Schwann cells, expression from the HCMV major IE promoter-enhancer in the replication-deficient Ad vector was activated by superinfection with HSV-1, replication-competent Ad and HCMV. The HCMV major IE promoter-enhancer was active in neurons when inserted into HSV-1 recombinant vectors. Further experiments with HSV-1-derived amplicons strongly suggested that an IE protein was responsible for the activation of HCMV major IE-induced expression in neurons. This demonstrates that the activity of the HCMV major IE promoter-enhancer element can depend on the expression of other genes encoded in the virus vector backbone within which it is inserted, and that it can function in a neuronal cell type-specific manner when inserted into a replication-deficient Ad vector.
Adenoviridae↗
Integrin expression and function on human osteoblast-like cells.
The integrin family of cell adhesion molecules are a series of cell surface glycoproteins that recognize a range of cell surface and extracellular matrix (ECM)-associated ligands. To date, the precise role of individual integrin molecules in bone cell-ECM interactions remains unclear. Cell binding assays were performed to examine the ability of normal human bone cells (NHBCs) to adhere to different ECM proteins in vitro. NHBCs displayed preferential adhesion to fibronectin over collagen types I, IV, and vitronectin and showed low affinity binding to laminin and collagen type V. No binding was observed to collagen type III. The integrin heterodimers alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, alpha 5 beta 1, alpha v beta 3, and alpha v beta 5 were found to be constitutively expressed on the cell surface of NHBCs by flow cytometric analysis. The integrins alpha 4 beta 1 and alpha 6 beta 1 were not expressed by NHBCs. Subsequent binding studies showed that NHBC adhesion to collagen and laminin was mediated by multiple integrins where cell attachment was almost completely inhibited in the presence of a combination of function-blocking monoclonal antibodies (Mabs) to alpha 1 beta 1, alpha 2 beta 1, alpha 3 beta 1, and beta 1. In contrast, the adhesion of NHBCs to fibronectin was only partially inhibited (50%) in the presence of blocking Mabs to alpha 3 beta 1, alpha 5 beta 1, and beta 1. The attachment of NHBCs to collagen, laminin, fibronectin, and vitronectin was also found to be unaffected in the presence of a function-blocking Mab to alpha v beta 3. The results of this study indicate that beta 1 integrins appear to be the predominant adhesion receptor subfamily utilized by human osteoblast-like cells to adhere to collagen and laminin and in part to fibronectin.
Adult↗
Structure of a secreted aspartic protease from C. albicans complexed with a potent inhibitor: implications for the design of antifungal agents.
The three-dimensional structure of a secreted aspartic protease from Candida albicans complexed with a potent inhibitor reveals variations on the classical aspartic protease theme that dramatically alter the specificity of this class of enzymes. The structure presents: (1) an 8-residue insertion near the first disulfide (Cys 45-Cys 50, pepsin numbering) that results in a broad flap extending toward the active site; (2) a 7-residue deletion replacing helix hN2 (Ser 110-Tyr 114), which enlarges the S3 pocket; (3) a short polar connection between the two rigid body domains that alters their relative orientation and provides certain specificity; and (4) an ordered 11-residue addition at the carboxy terminus. The inhibitor binds in an extended conformation and presents a branched structure at the P3 position. The implications of these findings for the design of potent antifungal agents are discussed.
Amino Acid Sequence↗
Replication of scrapie in spleens of SCID mice follows reconstitution with wild-type mouse bone marrow.
SCID mice are resistant to intraperitoneal infection with 10(3) and 10(4) intracerebral ID50 units of ME7 scrapie agent whereas they develop disease after intracerebral challenge. However, higher doses introduced, by intraperitoneal or subcutaneous routes, produce disease. Immunocompetent mice of the same strain (CB20) developed scrapie following either intracerebral or intraperitoneal infection. Bioassay of spleens from SCID mice infected with 10(-1) dilutions of ME7 scrapie by intraperitoneal, intracerebral or abdominal subcutaneous injection showed traces or low levels of infectivity in spleen. However, subcutaneous injection beneath the skin of the neck failed to infect the spleen. CB20 bone marrow reconstitution of SCID mice resulted in the regeneration of a normal lymphoid architecture in the spleen. Spleens from these reconstituted mice, infected intracerebrally with a 10(-1) dilution of ME7 contained high levels of infectivity. These results suggest that the ability to replicate scrapie agent in spleen or lymphoid tissue depends on the restoration of normal lymphoid structure and in particular the presence of differentiated follicular dendritic cells. The possibility that SCID mice can select minor strains of scrapie which are normally unrecognized in cloned ME7 is discussed.
Animals↗
Advice about management of skin conditions in the community: who are the providers?
A survey was undertaken in the central Victorian city of Maryborough to investigate the use of pharmacies and general practitioners as sources of advice about skin problems. In a 2 week period consumers purchasing either prescription or over the counter (OTC) products for skin, hair and nails in pharmacies were approached for interview. Simultaneously, each of the city's general practitioners (GP) completed questionnaires on all patients presenting with conditions of skin, hair and nails. Seventy per cent of the 315 consumers interviewed were purchasing OTC products and 50% prescription items. Of the OTC products, 42% were originally recommended by pharmacy staff and 18% by doctors. Over one-third of consumers buying OTC products described symptoms to pharmacy staff and in about half of the cases it was to the pharmacy assistant. One-third of people describing symptoms had already seen a doctor. Problems most frequently reported were dermatitis, skin dryness, acne and tinea. General practitioners recorded 265 conditions (of which 54% were new) in patients. The most common condition treated was solar keratosis, and GP wrote a prescription for 45% and recommended OTC products for 7% of conditions. People in Maryborough are seeking advice for their skin conditions from a variety of sources including GP, pharmacies and others.
Australia↗
Role of Borrelia burgdorferi in the pathogenesis of morphea/scleroderma and lichen sclerosus et atrophicus: a PCR study of thirty-five cases.
Morphea (localized scleroderma), and lichen sclerosus et atrophicus (LSA) share common features with acrodermatitis chronica atrophicans (ACA), a known chronic form of borreliosis. These include similar histologic findings such as diffuse dermal fibrosis. These observations have led several investigators to consider the possibility of Borrelia burgdorferi (Bb) as a common etiologic factor among all of these diseases. The aim of this study is to investigate the role of Bb in the pathogenesis of morphea and LSA, by assaying for its presence in lesional skin biopsies from patients with these diseases. We utilized the nested polymerase chain reaction (PCR) technique to selectively amplify a longer segment of a Bb-specific somatic gene, on DNA from paraffin-embedded, formalin-fixed tissues. The results revealed no Bb-specific DNA sequence in 28 specimens of morphea/scleroderma and 7 of LSA with varying stages of disease. Furthermore, confirmatory Southern blot of the PCR product, resulted in similar findings. These data seriously question the role played by this spirochete in the pathogenesis of morphea and LSA, at least in the southeastern part of the USA.
Adult↗
Cardiopulmonary resuscitation in the elderly.
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Aged↗
Ethics and economics of health care. British medicine has lessons for North American medicine.
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Decision Making↗
A middle stone age worked bone industry from Katanda, Upper Semliki Valley, Zaire.
Three archaeological sites at Katanda on the Upper Semliki River in the Western Rift Valley of Zaire have provided evidence for a well-developed bone industry in a Middle Stone Age context. Artifacts include both barbed and unbarbed points as well as a daggerlike object. Dating by both direct and indirect means indicate an age of approximately 90,000 years or older. Together with abundant fish (primarily catfish) remains, the bone technology indicates that a complex subsistence specialization had developed in Africa by this time. The level of behavioral competence required is consistent with that of upper Paleolithic Homo sapiens sapiens. These data support an African origin of behaviorally as well as biologically modern humans.
Animals↗
Parvovirus B19 outbreak in a developmental center.
Of 49 employees serving developmentally disabled persons, 13 (27%) were found to have parvovirus B19 infection on the basis of serum positivity for parvovirus B19 IgM by enzyme-linked immunosorbent assay. Two employees had severe peripheral symmetric polyarthropathy lasting longer than 6 months. Infection control measures are described.
Adult↗
From research to practice: the effects of the jointly sponsored dissemination of an arthritis self-care nursing intervention.
Various educational programs have been developed and found to be effective in the self-management of arthritis. This study reexamined the effectiveness of one such program, "Bone Up On Arthritis" (BUOA), when the program was delivered by a community-based service organization to a sample of persons (N = 154) who differed widely in disease type and demographic characteristics. Arthritis Foundation staff implemented BUOA at four national sites; data were collected and analyzed by University of Michigan nurse researchers. Investigators found improved scores on all outcome measures (self-care behavior, helplessness, pain, dysfunction, and depression). These findings suggest that "Bone Up" is an effective nursing intervention in multiple organizational and community environments and for diverse patient populations.
Aged↗
Discussing cardiopulmonary resuscitation with patients and relatives.
This paper aims to give clear guidance for doctors working in the UK about their responsibilities when discussing cardiopulmonary resuscitation with patients and their relatives. The ethical and legal framework for making decisions is outlined and the commonly encountered dilemmas are discussed.
Aged↗
VLA integrin expression in normal and diseased human kidney: how should we interpret immunohistochemical data?
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Antibodies, Monoclonal↗
Criteria-based antimicrobial i.v. to oral conversion program.
Collaborative efforts among several departments and the P & T Committee resulted in an IV to oral conversion program for select antimicrobials in our 580-bed county teaching hospital. This criteria-based program was designed to monitor and educate physicians on the appropriateness of parenteral antimicrobial prescribing, ensure rapid transition from IV to oral therapy, and contain costs. In the first 2 months of the program, 78 patients were converted from IV to oral administration with an estimated savings of $12,935. Of the ordering physicians, 66 (84.6%) accepted the interventions. All patients who switched administration routes were successfully treated with an oral agent. This program also has had a positive effect on patient outcomes and physician prescribing habits.
Administration, Oral↗