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Biomedical subjects

J Walter

Publications and source records attributed to J Walter.

At least 91 records · Page 5Linked to original sources

Potyvirus helper component-proteinase self-interaction in the yeast two-hybrid system and delineation of the interaction domain involved.

Using the yeast two-hybrid system, a screen was performed for possible interactions between the proteins encoded by the 5' region of potyviral genomes [P1, helper component-proteinase (HC-Pro), and P3]. A positive self-interaction involving HC-Pro was detected with lettuce mosaic virus (LMV) and potato virus Y (PVY). The possibility of heterologous interaction between the HC-Pro of LMV and of PVY was also demonstrated. No interaction involving either the P1 or the P3 proteins was detected. A series of ordered deletions from either the N- or C-terminal end of the LMV HC-Pro was used to map the domain involved in interaction to the 72 N-terminal amino acids of the protein, a region known to be dispensable for virus viability but necessary for aphid transmission. A similar but less detailed analysis mapped the interacting domain to the N-terminal half of the PVY HC-Pro.

Binding Sites↗

Increased generation of CD8+ T cell clones in p53 mutant mice.

Very few cultured CD8+ T cell clones can normally be obtained from a single mouse and maintained in long-term culture. To improve the yield, we immunized p53 mutant mice with peptides of Sendai virus (FAPGNYPAL) and influenza virus (ASNENMETM) origin. Substantially more clones could be derived from p53-/- mice than from similarly treated wild-type mice (p53+/+); an intermediate yield was obtained from heterozygous mice (p53+/-). CTL lines or clones from p53-/- mice exhibited greater proliferative activity and resistance to gamma-irradiation than those from p53+/+ mice, and were cytolytically potent.

Animals↗

Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis.

Mutations within the Presenilin-2 (PS-2) gene are associated with early onset familial Alzheimer's disease. The gene encodes a polytopic transmembrane protein that undergoes endoproteolytic processing resulting in the generation of N-terminal and C-terminal fragments (CTFs). PS-2 is also cleaved by proteases of the caspase family during apoptotic cell death. CTFs of PS-2 were shown to inhibit apoptosis, suggesting an important role in the regulation of programmed cell death. Recently, we found that the CTF of PS-2 is phosphorylated in vivo. We mapped the in vivo phosphorylation sites of PS-2 to serine residues 327 and 330, which are localized immediately adjacent to the cleavage sites of caspases after aspartate residues 326 and 329. Phosphorylation of PS-2 inhibits its cleavage by caspase-3. This effect can be mimicked by substitutions of serines 327 and 330 by aspartate or glutamate. In addition, the uncleavable form of PS-2 CTF was found to enhance its antiapoptotic properties, leading to a slower progression of apoptosis. These results demonstrate that PS-2 cleavage as well as its function in apoptosis can be regulated by protein phosphorylation. Alterations in the phosphorylation of PS-2 may therefore promote the pathogenesis of AD by affecting the susceptibility of neurons to apoptotic stimuli.

Amino Acid Sequence↗

Oncocytic myoepithelioma and pleomorphic adenoma of the salivary glands.

Twenty oncocytic myoepitheliomas (MEs) and pleomorphic adenomas (PAs) were composed of interlacing fascicles of swollen spindle-shaped or/and epithelioid oncocytic myoepithelial cells showing intense finely granular immunoreactivity with anti-mitochondrial antibody. Focal vacuolation of the cytoplasm of oncocytic myoepithelial cells and their gradual transition into sebaceous metaplasia were observed in 3 cases. Another unusual feature found in 5 cases was the presence of slit-like adenomatoid spaces lined with double-layered oncocytic myoepithelium closely resembling Warthin's tumour. The nuclei of oncocytic cells were characterized by enlargement, hyperchromasia and polymorphism, which should not be confused with malignancy. Oncocytic change in myoepithelial cells in MEs and PAs can cause pitfalls in the differential diagnosis of salivary gland tumours. We describe some unusual histological features associated with onococytic metaplasia in benign myoepithelial cell-derived salivary gland tumours, hoping to help to avoid the overdiagnosis of malignancy.

Adenoma, Pleomorphic↗

Older patients' health-related quality of life around an episode of emergency illness.

STUDY OBJECTIVES: We sought to describe older patients' health-related quality of life during a 4-month period surrounding a visit to the emergency department and to identify factors associated with less recovery. METHODS: We prospectively studied 983 patients 65 years or older who presented to an urban academic ED in 1995 and 1996. Eighty percent of the patients were African American, and 63% were women. The primary outcome measures were the Katz Index of Activities of Daily Living and revised validated questions from the Medical Outcomes Study Health Survey at 1 month before the ED visit, the time of the ED visit, and 2-week and 3-month follow-up periods. RESULTS: In general, patients worsened markedly during the illness and then improved, although not to baseline levels. After adjustment for demographic and social factors, the most consistently powerful predictors of poor recovery were more deficiencies in activities of daily living at baseline, reports of needing more help with everyday tasks, increasing Charlson Comorbidity Index scores, and requiring a proxy for the initial survey. CONCLUSION: Emergency physicians and primary care physicians should consider inquiring about functional status and the adequacy of help at home in addition to comorbid conditions for their acutely ill older patients to target those at greatest risk for poor recovery. Future work needs to test interventions that may improve the health-related quality of life of these vulnerable patients.

Activities of Daily Living↗

The effect of alcohol abuse on the health status of older adults seen in the emergency department.

OBJECTIVE: To examine the effect of alcohol abuse on the subsequent health status of elderly patients seen in an emergency department (ED). PATIENTS AND METHODS: A sample of 966 patients aged 65 or older who presented to one urban academic ED between the hours of 8 A.M. and 12 midnight was followed for 1 year. A personal interview was administered during the ED visit. Current problem drinkers had a score of 1 or greater on the CAGE questionnaire at ED presentation and drank within the prior 6 months; former problem drinkers had a score of 1 or greater on the CAGE questionnaire at ED presentation and a last drink more than 6 months previously. We used 13 items from the Medical Outcomes Study short form adapted to the ED setting and 6 items from the Index of Activities of Daily Living (ADL) to measure health status. RESULTS: In multivariate models for repeated-measures controlling for potential confounding factors, current problem drinkers had worse overall health (parameter estimate beta -3.6; 95% CI -7.1 to -0.04), and former problem drinkers had worse mental health (beta -3.6; CI -6.9 to -0.24) on follow-up. We could find no effect of problem drinking on physical health or social function. CONCLUSIONS: Current problem drinking is associated with worse self-perceived health among elderly patients in the year following presentation to an ED. The magnitude of decline in health perception may approximate the effect of having back pain, sciatica, or other musculoskeletal complaints. Elderly former problem drinkers suffer from more severe mental health problems over that same period.

Activities of Daily Living↗

Panel of microsatellite markers for whole-genome scans and radiation hybrid mapping and a mouse family tree.

To facilitate whole-genome scan experiments, we selected a panel of 128 microsatellite markers on the basis of spacing and polymorphism in the strains DBA/2, BALB/c, AKR, C57BL/6, C57BL/10, A/J, C3H, 129/J, SJL/J, JF1, and PWB. Many of the primer pairs were redesigned for better performance. The last four strains were not characterized previously using these markers. JF1 and PWB are particularly interesting for intersubspecific crosses offering high polymorphism. We provide allele size data for the markers on these strains and add them to the emerging radiation hybrid framework map, which is not continuous except for chromosome 17 and 13. Information on the interrelationships of strains is useful both because of the importance of polymorphism in designing crosses and the background in assessing phenotypes. Microsatellites offer a widely dispersed, selectively neutral set of characters that lends itself conceptually to parsimony methods of analysis. The microsatellite allele size data were recoded as binary discrete characters in such a way that adjacent sizes differ by one step. Trees were generated using a Wagner parsimony method. As expected, the non-Mus domesticus strains, PWB (musculus) and JF1 (molossinus), are excluded from the domesticus strains. Among the domesticus strains, C57BL/6 and C57BL/10 (derived from the same founding pair) form a strongly supported group, as do C3H, A/J, and BALB/c (derived from the Bagg albino stock). No unique branching order for SJL/J, AKR, and DBA/2 is strongly supported, which may reflect a complicated history. Strain 129/J is clearly placed as the most deeply diverged of the domesticus strains represented.

Alleles↗

Appropriateness of medication selection for older persons in an urban academic emergency department.

OBJECTIVES: To determine the frequency of potentially inappropriate medication selection for older persons presenting to the ED, the most common problematic drugs, risk factors for suboptimal medication selection, and whether use of these medications is associated with worse outcomes. METHODS: The authors performed a prospective cohort study of 898 patients 65 years or older who presented to an urban academic ED in 1995 and 1996. Seventy-nine percent of the patients were African-American and 43% did not graduate from high school. Potentially inappropriate medications and adverse drug-disease interactions were identified using the 1997 Beers explicit criteria for elders. During the three months after the initial visit, revisits to the ED or hospital, death, and changes in health-related quality of life were analyzed as measured by validated questions adapted from the Medical Outcomes Study. RESULTS: Upon presentation, 10.6% of the patients were taking a potentially inappropriate medication, 3.6% were given one in the ED, and 5.6% were prescribed one upon discharge from the ED. The most frequently prescribed potentially inappropriate medications in the ED were diphenhydramine, indomethacin, meperidine, and cyclobenzaprine. Emergency physicians added potentially inappropriate medications most often to patients with discharge diagnoses of musculoskeletal disorder, back pain, gout, and allergy or urticaria. Potentially adverse drug-disease interactions were relatively uncommon at presentation (5.2%), in the ED (0.6%), and on discharge from the ED (1.2%). Potentially inappropriate medications and adverse drug-disease interactions prescribed in the ED were not associated with higher rates of revisit to the ED, hospitalization, or death, but were correlated with worse physical function and pain. However, confidence intervals were wide for analyses of revisits and death. CONCLUSIONS: Suboptimal medication selection was fairly common and was associated with worse patient-reported health-related quality of life.

Accidental Falls↗

Immunization outreach in an inner-city housing development: reminder-recall on foot.

OBJECTIVE: To determine rates of immunization coverage among children 3 to 72 months of age in a large public housing development, to develop a community-based outreach program to increase coverage, and to evaluate the effect of the program. DESIGN: A door-to-door canvass of the development by specially trained emergency medical technicians to enroll families, to determine immunization status from written records, and to follow-up to encourage immunizations and well-child care. The program was evaluated, comparing rates of immunization by age with an expectation based on the immunization histories before enrollment. SETTING: A Chicago public housing development, October 1993 through December 1996. OUTCOME VARIABLES: Antigen-specific and series-specific coverage based on written records. RESULTS: Of the caregivers, 92% were able to identify a primary care provider. At the time of enrollment, 37% of 1075 children were up-to-date, but that proportion varied by age with 27% of children 19 to 35 months of age being up-to-date. The program increased rates of immunization compared with the expectation from the preenrollment rates. At their final assessment, 50% of the children were up-to-date. For individual vaccines, there was a positive program effect. For example, before enrollment, 22% of children 15 months of age had received measles, mumps, and rubella vaccine. However, 39% of children who were enrolled in the program before they were 12 months of age had received their first immunizations by 15 months of age. CONCLUSIONS: Children in the housing development had very low rates of immunization before enrollment. An in-person intervention was effective in reaching families and determining immunization status. In the 3-year enrollment and observation period, rates of immunization increased.

Chicago↗

[Elephant herpes virus--a problem for breeding and housing of elephants].

Herpesvirus infections which take a fatal turn on African elephants as well as on Asian elephants seem to occur increasingly not only in the USA but also in European stocks. The endotheliotropic herpesvirus causes a rapidly progressing and severe disease which makes any therapeutical effort unsuccessful and finally results in death of the animal, especially in young Asian elephants. As all attempts to culture the virus failed up to now, molecular biological procedures have to be used more often for diagnostical purpose together with the common methods of pathology, virology, and electronmicroscopical evaluation. This is a report on the case of 'KIBA', an eleven year old male elephant at the Zoological Garden Berlin, infected with the endotheliotropic elephants herpesvirus. 'KIBA' was born at the Zoo in Houston, Texas, and raised within his herd. Upon arriving in Berlin in November 1997 he adapted to the new premises and climate and new social circumstances without any problems. In June 1998 he already serviced three females of his new herd several times. In August 1998 he died after passing a peracute progression of the disease after residenting in Berlin for only 9 months. The dissection of the animal revealed some evidence on an agent damaging the endothelium. Major signs indicating this agent were bleedings in several serous membranes, mucosa and on the the right atrium, as well as other parts of the myocardium. Furthermore there have been ulcerations at various localisations of the whole digestive tract. Slightly basophilic intranuclear inclusion bodies have been found histologically in endothelial cells of different organ samples. An examination of altered organ-material by electronmicroscopy made some herpesvirus-like particles visible. A virological investigation first revealed evidence of giant cell formations with solitary basophilic intranuclear inclusion bodies in different cell cultures, however, without any distinct cytopathogenic effect. Supported by molecular biological procedures the infection of 'KIBA' could be verified as the elephants herpesvirus. By means of PCR and subsequent sequence analysis a DNA-sequence typical for the elephants herpesvirus could be obtained which showed an identity of 97% with the terminase sequence of the elephant herpesvirus described by American authors. The deduced amino acid-sequences were 100% identical. To the terminase of the human cytomegalovirus, the elephant sequence had an identity of 53% (similarity: 74%). Based on the cooperation of ILAT, Institute of Veterinary-Pathology/Free University Berlin, Robert-Koch-Institut Berlin, and Zoological Garden Berlin, the cause of 'KIBA's' death could be discovered immediately. Possible implications of this case especially on breeding and keeping elephants are discussed briefly.

Amino Acid Sequence↗

Elastofibroma dorsi. Study of two cases and magnetic resonance imaging findings.

Two cases of elastofibroma dorsi (one bilateral, one unilateral) in the periscapular and infrascapular region of two male patients are described. Magnetic resonance imaging revealed a tumorous mass of typical low signal intensity with interspersed areas of high signal intensity on T1 and T2 weighted spin echo sequences. In contrast to previous studies that reported mild enhancement within elastofibromas after administration of intravenous contrast agent, marked enhancement in one of two elastofibromas was found. This is considered to be atypical for benign lesions. After biopsy and histopathologic examination, an intended marginal resection was performed in both cases. Laboratory values, radiographs, and computed tomography may not be helpful in differentiating elastofibroma from malignant tumors. In addition to careful clinical investigation, magnetic resonance imaging is the method of choice leading to a presumptive diagnosis. Because marked enhancement on contrast agent images was observed, which is characteristic for malignant tumors, one should be aware that this feature does not exclude the presence of elastofibroma. Accurate diagnosis should be made preferably by biopsy and histopathologic evaluation before additional treatment is administered. Marginal resection is curative in patients with symptoms. Despite its low incidence, this pseudotumoral lesion should be known generally to differentiate it from malignant tumors and to avoid unnecessary wide or radical surgery.

Back↗

Laser therapies in dermatology.

BACKGROUND: Early lasers used in dermatology were continuous wave, with high energy focused in a small area, and did not utilise target specific wavelengths. They caused significant thermal injury to the skin surrounding the target. Over the past 8 years the safety of dermatological lasers has been enhanced by addressing these problems. OBJECTIVE: To discuss the advances in laser technology and the clinical uses of these new devices. DISCUSSION: Modern lasers are designed with a wavelength specific for thermally destroying a particular target without significantly damaging surrounding tissues (selective thermolysis). Electronic systems have been developed which deliver short pulse duration energy sufficient to damage target tissue but limiting thermal conduction to surrounding tissues. These advances have made treatment of vascular and pigmented lesions and resurfacing techniques safer.

Humans↗

Cell/adsorbent interactions in expanded bed adsorption of proteins.

Expanded bed adsorption (EBA) is an integrated technology for the primary recovery of proteins from unclarified feedstock. A method is presented which allows a qualitative and quantitative understanding of the main mechanisms governing the interaction of biomass with fluidized resins. A pulse response technique was used to determine the adsorption of various cell types (yeast, Gram positive and Gram negative bacteria, mammalian cells and yeast homogenate) to a range of commercially available matrices for EBA. Cells and cell debris were found to interact with the ligands of agarose based resins mainly by electrostatic forces. From the adsorbents investigated the anion exchange matrix showed the most severe interactions, while cation exchange and affinity adsorbents appeared to be less affected. Within the range of biologic systems under study E. coli cells had the lowest tendency of binding to all matrices while hybridoma cells attached to all the adsorbents except the protein A affinity matrix. The method presented may be employed for screening of suitable biomass/adsorbent combinations, which yield a robust and reliable initial capture step by expanded bed adsorption from unclarified feedstock.

Adsorption↗