Mononucleotide repeat polymorphism in the APP gene.
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Biomedical subjects
Publications and source records attributed to M Owen.
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Accurate and consistent enumeration of B-cell subpopulations in lymphoid tissue was achieved through multiparameter three-color immunofluorescence and flow cytometric analysis (FCM). Phycoerythrin (PE)-anti-CD19 (Leu12) and biotinylated anti-HLADr/streptavidin-Duochrome (PE/Texas Red), used in conjunction with polyclonal fluorescein isothiocyanate (FITC) conjugated anti-surface immunoglobulin (SIg) antibodies, effectively separated non-specific binding and background fluorescence from true B-cell surface FITC immunofluorescence, while concomitantly analyzing for HLADr and CD19 phenotypic expression/deletion. Autofluorescence was measured to establish a fluorescence threshold. A second control measured non-specific binding of isotypic control mouse Ig and non-immune rabbit IgG. Cell suspensions from 128 samples of various lymphoid proliferations were studied. In 116 of the 128 samples, kappa/lambda ratios determined by flow cytometry correlated well with immunocytology results obtained using cytospins from the same cell suspension and with histopathologically established diagnosis. Clonality and lineage as defined immunotypically by flow cytometry was concordant with genotypic results in 64 of the 67 cases evaluated. SIg, HLADr, and CD19 deletions were demonstrated by flow cytometry in 8, 4, and 1 case(s), respectively. Discordance was usually attributable to selective loss of large neoplastic cells in flow cytometry specimens or absent expression of SIg by some cytoplasmic Ig (CIg+) lymphomas.
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1. Transcranial magnetic stimulation was performed using a figure-of-eight-shaped coil over the right motor cortex with the aim of identifying those areas involved with activation of the diaphragm. 2. The response of the right and left hemi-diaphragms was recorded using surface electrodes in either the 7th or 8th intercostal spaces 3 cm lateral to the anterior costal margin on either side. 3. The compound muscle action potentials recorded over the left diaphragm in response to transcranial magnetic stimulation were maximal when the centre of the figure-of-eight coil was placed approximately 3 cm to the right of the mid-line and 2-3 cm anterior to the auricular plane. 4. The amplitude of the response recorded from the diaphragm depended upon the angulation of the figure-of-eight coil and hence the direction of the stimulating current. 5. The response of the inspiratory muscles to magnetic stimulation of one side of the brain was predominantly contralateral but a small response was seen on the ipsilateral side. Ultrasonic techniques confirmed that the diaphragm was responding contralaterally and not ipsilaterally.
Close linkage of a hypervariable DNA probe on chromosome 4q (pH30, locus D4S139) has been found with the locus for facioscapulohumeral disease. Three recombinants were identified in a total of 140 meioses, giving a maximum lod score of 36.77 at a recombination fraction of 0.02. All but two of the families studied proved informative with this probe; all informative families showed evidence of linkage (except one family with a single scorable meiosis), making genetic heterogeneity unlikely from our data. The close linkage and highly informative nature of the probe will make it suitable for clinical application in presymptomatic and prenatal diagnosis. We have also confirmed loose linkage with the marker (Mfd22, locus D4S171) used to establish the initial assignment of the disorder to chromosome 4.
Pre-morbid schizoid and schizotypal traits and social adjustment were assessed blind to diagnosis by interviewing the mothers of 73 consecutively admitted patients with DSM-III schizophrenia or affective psychosis. Analysis of factors associated with pre-morbid deficits showed a highly significant interaction of diagnosis with sex, such that schizophrenic men showed much greater pre-morbid impairment than either schizophrenic women or men with affective disorder. Poor pre-morbid adjustment predicted an early age at first admission. The results can be explained by a neurodevelopmental disorder in some schizophrenic males.
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Three adult male patas monkeys (11-15 kg) were heat acclimated by continuous exposure to an ambient temperature of 33 +/- 1 degree C at 13% relative humidity for 9 mo. During the last month, they were also exposed to 45 degrees C at 10% relative humidity for 4 h/day and 5 days/wk. Before and after 3 wk of acclimation, the animals were given a heat-tolerance test in which rectal (Tre) and mean skin (Tsk) temperatures, heart rate, and sweat rate (msw) were monitored during a 90-min exposure to 45 degrees C heat with 24% relative humidity under lenperone (1.0-1.4 mg/kg im) tranquilization. Maximal in vivo msw was also determined in response to subcutaneous injections (1 and 10% solutions) of methacholine (MCh). Before and after 9 wk and 9 mo of acclimation, sweat glands were dissected from biopsy specimens of the lateral calf, cannulated, and stimulated in vitro with MCh. Morphological measurements of isolated tubules were compared with maximal secretory rates produced by MCh stimulation. Three weeks of acclimation 1) reduced Tre and Tsk and increased msw during the heat tolerance test and 2) significantly increased maximal msw in response to MCh stimulation. Acclimation also increased (P less than 0.05) sweat gland size, as measured by tubular length and tubular volume. Maximal in vitro msw produced by MCh stimulation and msw per unit length of secretory coil also increased significantly. We conclude that heat acclimation increases the size of eccrine sweat glands and that these larger glands produce more sweat. They are also more efficient because they produce more sweat per unit length of secretory coil.
"A considerable proportion of the variance in the liability to develop schizophrenia may be genetic, but segregation analysis, to establish a mode of transmission, has not produced a consistent result. One of these studies was carried out in Iceland and made use of the large family size and extensive genealogical information present in that country. Here we demonstrate genetic linkage of two DNA polymorphisms on the long arm of human chromosome 5 to schizophrenia in seven British and Icelandic families with multiple affected members. The results indicate the existence of a gene locus with a dominant schizophrenia-susceptibility allele. Inheritance of the allele in the families studied suggests that it may also predispose to psychiatric conditions such as schizophrenia spectrum disorders and a variety of other disorders. This report provides the first strong evidence for the involvement of a single gene in the causation of schizophrenia."
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We investigated whether monoclonal antibodies (MoAbs) reactive against both acidic and basic cytokeratins alone were sufficient to detect minimal numbers of contaminating epithelial tumor cells in the bone marrow of breast cancer patients. Monoclonal anti-cytokeratin antibodies (AE1 and AE3) were used to stain 14 breast carcinomas by the avidin-biotin-peroxidase technique. Nine tumors (64.3%) showed high reactivity and five (35.7%) showed low or moderate reactivity. Nine MoAbs that proved to be unreactive to light density bone marrow cells by immunoalkaline phosphatase histochemistry were screened for reactivity to breast carcinomas having only low or moderate positivity to cytokeratin antibodies. Three of nine MoAbs showed high percentages of positivity and were selected to supplement the anti-cytokeratin antibodies for immunohistochemical detection of minimal marrow disease in breast cancer patients. A MoAb cocktail was prepared, further tested for reactivity to another five breast carcinomas, and compared with cytokeratin staining alone. The cocktail labeled 100% of carcinoma cells in all the examined specimens. To determine the sensitivity of this panel for detecting minimal numbers of contaminating tumor cells in bone marrow, in vitro mixing experiments were performed. T47D breast carcinoma cells were mixed with bone marrow mononuclear cells at ratios from one tumor cell per 10 bone marrow cells up to one tumor cell per 1 x 10(6) marrow cells, and cytospin preparations were subsequently stained with the MoAb cocktail by the immunoalkaline phosphatase method. Our approach could detect one tumor cell in 1 x 10(5) hematopoietic cells.
Evidence is discussed for the hypothesis that there are stromal stem cells present in the soft connective tissues associated with marrow and bone surfaces that are able to give rise to a number of different cell lines including the osteogenic line. Fibroblastic colonies, each derived from a single colony-forming unit fibroblastic (CFU-F), are formed when marrow cells are cultured in vitro. In vivo assays of CFU-F have demonstrated that some CFU-F have a high ability for self renewal and multipotentiality whereas some have more limited potential. In vitro studies also support the hypothesis and have shown that CFU-F are a heterogeneous population of stem and progenitor cells and that their differentiation in vitro can be modified at the colony level. Factors added to the medium can activate osteogenesis in a range of multipotential and more committed precursors. Different stromal cell lines can be promoted under different culture conditions. The number and hierarchy of cell lines belonging to the stromal fibroblastic system are not yet fully elucidated and more specific markers for the different lines are required before a better understanding can be achieved.
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Evidence for the hypothesis that there are stromal stem cells present in the soft connective tissues associated with marrow and bone surfaces that are able to give rise to a number of different cell lines is reviewed. The lines are currently designated fibroblastic, reticular, adipocytic and osteogenic. Fibroblastic colonies, each derived from a single colony-forming unit fibroblastic (CFU-F), are formed when marrow cells are cultured in vitro. In vivo assays of tissue formed by CFU-F in open transplant or in diffusion chambers, have demonstrated that some CFU-F have a high ability for self renewal and multipotentiality whereas some have more limited potential. Preliminary investigations in vitro also support the hypothesis and have shown that CFU-F are a heterogeneous population of stem and progenitor cells and that their differentiation in vitro can be modified at the colony level. The stromal cells which survive and proliferate in vitro are highly dependent on culture conditions. The number and hierarchy of cell lines belonging to the stromal fibroblastic system are not yet fully elucidated and more specific markers and better assays for the different phenotypes are required before a greater understanding can be achieved. The possibility that the marrow stromal system is part of a wider stromal cell system of the body is proposed.
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Twenty-nine samples of food-aid biscuits were collected during a survey of feeding programmes in Ethiopia and Sudan. A further seven brands were included in the study but were not found in Ethiopia or Sudan. All but two brands were produced in Europe. Only 20 brands were recommended for use as emergency rations or as nutritious supplements; eight brands were similar to traditional baked biscuits and four were infant rusks. The compared biscuit characteristics included ingredients, energy density, unit size, protein content, fortification with vitamins and minerals and costs. A wide range in all characteristics was found. Biscuits high in protein tended to have a low energy density. Energy density and unit size influenced the volume eaten and ease of transport, storage and also distribution to recipients. The cost of energy (per 500 kcal) ranged between 14.0 p for baked biscuits and 47.5 p for the unbaked compressed products.
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