Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)] fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but to delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.     

Microdissection and microcloning of chromosomal alterations in human breast cancer

Summary The recognition of recurring sites of chromosome changes in malignancies has greatly facilitated the identification of genes implicated in the pathogenesis of human cancers. Based especially upon recent studies [1–4], it appears increasingly likely that a subset of recurring chromosome alterations will be recognized in human breast cancer. Currently recognized chromosome changes characterizing breast carcinoma include the recognition of cytologic features of gene amplification (e.g. double minutes [dmins] and homogeneously staining regions [HSRs]) [5–8]. As these and other chromosome regions are implicated in recurring abnormalities in breast cancer, it will become increasingly important to have band-or region-specific genomic libraries and probes in order to facilitate high resolution physical mapping and ultimately to clone breast cancer related genes [9]. Toward this end an important recent development in physical mapping has been the establishment of chromosome microdissection as a rapid and reproducible approach to rapidly isolate and characterize chromosome region-specific DNA, greatly facilitating the initial steps in positional cloning of disease-related genes [10–13]. In this brief report, we will highlight the application of chromosome microdissection to the generation of region-specific probes for both fluorescent in situ hybridization (FISH) and the generation of genomic microclone libraries. Additionally, efforts using this methodology to generate a microclone library encompassing the early onset breast/ovarian cancer (BRCA1) gene will be presented.Presented by Jeffrey M. Trent at the 16th Annual San Antonio Breast Cancer Symposium, San Antonio TX, USA, November 4, 1993; Minisymposium on Molecular Genetics in Breast Cancer.     

TTAGG Telomeric Repeats in Chromosomes of Some Insects and Other Arthropods

We studied the occurrence of the TTAGG telomere repeats by fluorescence in-situ hybridization (FISH) and Southern hybridization in ten insect species and two other arthropods. (TTAGG)_n-containing telomeres were found in three Lepidoptera species, the silkworm Bombyx mori (in which the telomeric sequence was recently discovered), the flour moth Ephestia kuehniella, and the wax moth Galleria mellonella, in one species of Hymenoptera, the honey bee Apis mellifera, in one species of Coleoptera, the bark beetle Ips typographus, in one species of Orthoptera, the locust Locusta migratoria, and in a crustacean, the amphipod Gammarus pulex. They were absent in another species of Coleoptera, the mealworm Tenebrio molitor, two representatives of Diptera, Drosophila melanogaster and Megaselia scalaris, a species of Heteroptera, the bug Pyrrhocoris apterus and a spider, Tegenaria ferruginea. Our results, which confirm and extend earlier observations, suggest that (TTAGG)_n was a phylogenetically ancestral telomere motif in the insect lineage but was lost independently in different groups, being replaced probably by other telomere motifs. In the Coleoptera this must have happened rather recently as even members of the same family, Curculionidae, differ with respect to the telomeric DNA.     

Assessment of borderzone ischemia with a combined MR imaging-MR angiography-MR spectroscopy protocol

We attempted to assess whether magnetic resonance imaging (MRI)-MR angiography (MRA)-MR spectroscopy (MRS) measurements can be used in the differentiation of patients in whom severe carotid lesions result in chronically hypoperfused regions and in whom the collateral capacity is sufficient to maintain a normal cerebral blood flow. Sixty-six patients with severe stenosis of the internal carotid artery (ICA) and 19 control subjects underwent MRI, 1H MRS, and MRA. Anaerobic metabolic changes in the middle cerebral artery (MCA) territory were studied by assessing N-acetyl-L-aspartate (NAA)/choline and lactate/ NAA ratios. Quantitative flow was measured in the ICA, in the basilar artery, and in the MCA. Thirty-four patients had borderzone infarcts, 16 patients had territory infarcts, and 16 patients had no infarcts on MRI. Patients with border-zone infarcts had significantly reduced flow in the ICA (P < 0.001) and in the MCA (P < 0.05) and decreased NAA/ choline ratios (P < 0.001) in non-infarcted regions compared with control subjects (P < 0.001) but also compared with patients with territory infarcts (P < 0.05) and patients without infarcts (P < 0.05). Flow measurements in the ICA and MCA and metabolic measurements in the MCA territory can be applied to select patients in whom cerebral perfusion pressure is insufficient to maintain normal cellular integrity.     

Informal caregiving for frail older people at home and in long-term care institutions: who are the key supporters?

This paper describes the extent of the informal caregiving unit for older people who are physically or mentally frail living in private households or resident in long-term care institutions using cross-sectional analysis of survey data. A total of 1444 people aged 65 years or more registered with a general practitioner (GP) in four areas in England and, consenting to the study, were screened for mental or physical frailty. Of 1127 older subjects living at home 7% reported receiving no informal support, 15% had a paid supporter only and 78% nominated a key informal supporter who helped with defined activities of daily living of whom 650 (74%) were interviewed. Only 13% nominated more than one informal supporter. Key supporters were spouses (38%), daughters (30%), sons (9%), daughters-in-law (4%), other relatives (11%) and friends and neighbours (8%). Of 317 frail older people resident in long-term care institutions 175 (55%) received a main visitor at least once a week of whom 132 (75%) were interviewed. Main visitors were spouses (11%), daughters (36%), sons (23%), daughters-in-law (2%), other relatives (24%) and friends (4%). Qureshi & Walker's (1989) hierarchical, decision-making model for selecting informal caregivers was applied to the data and correctly identified 85% of key informal supporters and 79% of main visitors interviewed. This large-scale comprehensive survey of informal care for frail older people supports earlier small-scale localized studies highlighting the key role of spouses and daughters in the provision of informal support. Families of frail older people provide the support to maintain people at home.     

Improvement of brain single photon emission tomography (SPET) using transmission data acquisition in a four-head SPET scanner

Attenuation coefficient maps (-maps) are a useful way to compensate for non-uniform attenuation when performing single photon emission tomography (SPET). A new method was developed to record single photon transmission data and a-map for the brain was produced using a four-head SPET scanner. Transmission data were acquired by a gamma camera opposite to a flood radioactive source attached to one of four gamma cameras in the four-head SPET scanner. Attenuation correction was performed using the iterative expectation maximization algorithm and the-map. Phantom studies demonstrated that this method could reconstruct the distribution of radioactivity more accurately than conventional methods, even for a severely non-uniform-map, and could improve the quality of SPET images. Clinical application to technetium-99m hexamethylpropylene amine oxime (HMPAO) brain SPET also demonstrated the usefulness of this method. Thus, this method appears to be promising for improvement in the image quality and quantitative accuracy of brain SPET.This work was presented in part at the World Congress on Medical Physics and Biomedical Engineering, 7–12 July 1991, Kyoto, Japan     

Differential motion hyperacuity under conditions of common image motion

Sensitivity to horizontal shearing motion in random dots was measured as a function of common image motion amplitude. Without common image motion, thresholds for differential motion are comparable or better than vernier acuity. Above about 2 arc min of common image motion there is a proportionate increase in motion parallax thresholds such that for 20 arc min of common image motion, differential motion thresholds have risen by an order of magnitude. This differs from a comparable lack of threshold elevation for vernier acuity targets under similar conditions of movement (Westheimer and McKee, 1975). By varying movement duration, it can be shown that common image motion amplitude rather than common image velocity is the primary determinant of the effect. Furthermore this degradation of performance is not affected by changes in random dot size. Under favorable circumstances the phenomenon can also be seen with differentially moving vernier lines. The effect shows directional selectivity such that common motion directions closest to the horizontal leads to the greatest interference. The results add weight to the view that differential motion hyperacuity is mediated by a separate mechanism than differential position hyperacuity.     

Oxidative damage on DNA induced by asbestos and man-made fibers in vitro

Summary We compared the potential of asbestos and man-made fibers to attack DNA by the determination of the yield of 8-hydroxy-2-deoxyguanosine (8-OH-dGuo) under several in vitro conditions. Asbestos induced 6.6–99.8 of 8-OH-dGuo per 10⁵ dGuo in calf thymus DNA after 20 h of incubation, while the levels of 8-OH-dGuo in man-made fibers were low (3.6–9.4). The amounts of 8-OH-dGuo were strongly stimulated by the addition of H₂O₂ in asbestos, but not in man-made fibers. However, the yield of 8-OH-dGuo was induced more than that with asbestos by the further addition of FeSO₄ in attapulgite, fiberglass, potassium titanate whisker, and metaphosphate polymer. The addition of ethylene diamine tetraacetic acid (EDTA) promoted the induction of 8-OH-dGuo with asbestos and H₂O₂. The effects of mannitol (known as a hydroxy radical scavenger) were not dramatic on 8-OH-dGuo induction by all fibers except fiberglass and basic magnesium sulfate whisker, which induced higher amounts after mannitol addition than in these fibers and H₂O₂. Therefore, it was suggested that asbestos could damage DNA, resulting in 8-OH-dGuo as a cause of point mutation, and also several types of manmade fibers had similar effects to asbestos under certain conditions.     

New strategies in immunosuppression

This article reviews recent papers relating to immunosuppressives and attempts to categorise the bewildering number of new reagents according to their effects on the immune response. It is apparent that the majority of groups are concentrating on reagents which, like cyclosporin A, are predominantly directed at T cells (42% of the last 200 papers inTransplantation, Transplant International andTransplantation Proceedings). The major change in strategy which is occurring relates to the rapidly increasing use of reagents directed against T cell subsets, especially those directed against the interleukin-2 receptor and CD4-positive T cells. This groups's share of the market has risen from 2% to over 12% within 5 years. New successful monoclonal antibodies include reagents directed against antigen-presenting cells and against molecules directly involved in cell adherence. The use of donor bone marrow or subsets of cells from donor bone marrow as inducers of non-reactivity, especially to solid organ grafts, is certainly one of the most exciting of the non-antibody protocols. It is encouraging that relatively specific immunosuppression can be induced in animals by combinations of specific and non-specific reagents as well as by specific reagents alone. This will facilitate the introduction of specific protocols into the human situation, and this strategy holds out great hope for the future. Unfortunately, one of the most effective ingredients of such combination therapies in animal models (anti-CD4) appears to have its tolerogenic potential abrogated by cyclosporin A and FK-506. One area of immunosuppression which is receiving scant interest relates to antibody (especially non human leucocyte antigen antibody) production, but as the interest in xenotransplantation increases it is anticipated that major new interest will emerge in this area.