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D Whitaker

Publications and source records attributed to D Whitaker.

At least 73 records · Page 4Linked to original sources
PubMed1992

Sequential mapping of weighting functions for visual location.

The effect upon perceived location of adding an extra dot offset from the centre of a cluster of pseudorandom dots was investigated using a vernier acuity task. With this technique, weighting functions showing the extent to which the added dot pulls the apparent location of the entire cluster can be defined as a function of distance from the centre of the cluster. When dot density within the cluster is high, the weighting functions approximate to what would be expected on the basis of centroid alignment. With low dot densities, it appears that performance is determined by aligning the outermost dots within each cluster. The peak amplitudes of these weighting functions are proportional to the square root of dot density within the clusters. The results are consistent with the view that each vernier element is localised in an orthoaxial direction prior to discrimination of the vernier offset.

Humans↗
PubMed1992

Clinical contrast sensitivity chart evaluation.

Three different types of contrast sensitivity chart were used on normal patients by six optometrists in clinical practice. The charts were the Vistech, the Pelli-Robson and the Cambridge low-contrast gratings test. We examine the data in terms of the differences between optometrists and the variation of contrast sensitivity with the age of the patient. There was a highly significant difference between the scores from different optometrists for all three charts. We attribute this to variability in measurement technique. There was also a highly significant effect of age for all three charts, with older observers tending to exhibit lower contrast sensitivity. On the Vistech chart, this sensitivity deficit was most pronounced at higher spatial frequencies. The level of redundant information in the tests is discussed.

Adolescent↗
PubMed1992

Variations in hyperacuity performance with age.

The term hyperacuity has been applied to a group of stimuli which produce spatial thresholds smaller than those expected given the relatively large receptor spacing and the retinal image quality of the human eye. It is not yet firmly established whether hyperacuity performance declines with increasing age in the same way as most other measures of visual ability. This is perhaps due to the use of varying task configurations and criterion-dependent psychophysical techniques. The present study examines age-related performance in three different hyperacuity tasks using a criterion independent forced-choice method. Both displacement and bisection thresholds were found to increase with age, but there was no significant change in vernier acuity. This indicates that age has a differential effect on thresholds for various hyperacuities depending upon the task requirements. No significant age-related trend was observed in hyperacuity bias, which represents the difference between subjective and true physical alignment.

Adolescent↗
PubMed1992

The concept of mesothelioma in situ: implications for diagnosis and histogenesis.

The concept of mesothelioma in situ is explored by a detailed examination of seven patients, subsequently proven to have pleural malignant mesothelioma, who initially had no evidence of gross tumor and for whom biopsy material was available at this early presentation. The tissue was assessed by routine microscopy, the immunoperoxidase technique for epithelial membrane antigen and silver staining for nucleolar organizer regions. Tiny lesions of the pleura that merged with or were adjacent to microscopically flat monolayered or folded mesothelium with cytological atypia were observed. The atypical cells reacted positively to epithelial membrane antigen, and the nucleolar organizer region counts were elevated. These observations are considered to support the possibility of the presence of mesothelioma in situ. These findings are discussed in the light of the proposed concept of mesothelioma in situ, its histogenesis, and its possible clinical relevance.

Adult↗
PubMed1991

Induction of local inflammation by recombinant human platelet factor 4 in the mouse.

Platelet factor 4 (PF-4) has been shown to be chemotactic for neutrophils and monocytes in vitro. To assess whether these observations have in vivo relevance, we tested the ability of recombinant human PF-4 (rPF-4) to induce acute and chronic dermal inflammation in the mouse. When injected as a single dose intradermally, rPF-4 induced an acute inflammatory response that peaked at 6 to 12 hr and which resolved by 36 hr. Injection of an equivalent amount of cytochrome c, buffer alone, or an amino-terminal PF-4 peptide failed to elicit a significant inflammatory response; however, the carboxy-terminal PF-4 peptide retained proinflammatory properties. The inflammatory infiltrate induced by a single injection of either rPF-4 or the 41 amino acid carboxy-terminal peptide was composed of neutrophils and smaller numbers of mononuclear cells. Repeated injection of rPF-4 resulted in nearly equal numbers of neutrophils and mononuclear cells. Moreover, marked dermal fibrosis developed after only 5 days of daily injection of rPF-4. Although relatively high concentrations of rPF-4 were required to elicit an inflammatory response, these concentrations may be locally attainable during platelet aggregation. Our findings thus support the hypothesis that PF-4 may contribute to the development of inflammatory responses at sites of platelet aggregation.

Animals↗
PubMed1991

Interaction between dactinomycin and tumor necrosis factor in mesothelioma. Cachexia without oncolysis.

There is no effective therapy for human malignant mesothelioma, and its susceptibility to recombinant cytokines has not been studied extensively. Recombinant human tumor necrosis factor alpha (rHuTNF alpha) was evaluated for its in vitro and in vivo antitumor activity using a human malignant mesothelioma cell line [DeH128(m)], both in culture and heterotransplanted in nude mice. In vitro, rHuTNF alone had no direct antimesothelioma activity assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide assay, but in combination with the transcription inhibitor, dactinomycin (AD), mesothelioma cell metabolic activity was inhibited (80% of control). The effects of this combination of agents were studied on DeH128(m) cells heterotransplanted as subcutaneous tumors in nude mice. In vivo there was no significant inhibition of tumor growth by combined rHuTNF alpha and AD therapy, but the combination produced marked cachexia in doses at which each component (rHuTNF alone or AD alone) was well tolerated. The authors conclude that the well-described in vitro interaction between AD and rHuTNF also operates in vivo to produce cachexia and that the combination of these two agents is likely to have a low therapeutic index in malignant mesothelioma.

Animals↗
PubMed1991

Human dermal mast cells contain and release tumor necrosis factor alpha, which induces endothelial leukocyte adhesion molecule 1.

Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine that mediates endothelial leukocyte interactions by inducing expression of adhesion molecules. In this report, we demonstrate that human dermal mast cells contain sizeable stores of immunoreactive and biologically active TNF-alpha within granules, which can be released rapidly into the extracellular space upon degranulation. Among normal human dermal cells, mast cells are the predominant cell type that expresses both TNF-alpha protein and TNF-alpha mRNA. Moreover, induction of endothelial leukocyte adhesion molecule 1 expression is a direct consequence of release of mast cell-derived TNF-alpha. These findings establish a role for human mast cells as "gatekeepers" of the dermal microvasculature and indicate that mast cell products other than vasoactive amines influence endothelium in a proinflammatory fashion.

Cell Adhesion↗
PubMed1991

Origins of BSE.

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Animal Feed↗
PubMed1991

Establishment and characterization of five human malignant mesothelioma cell lines derived from pleural effusions.

Malignant mesothelioma (MM) is an aggressive tumour of the serosal cavities which is associated with exposure to asbestos. Studies of this tumour have been limited by a paucity of well-characterized human MM cell lines. In this study, 5 human MM cell lines were established from pleural effusions of patients with this malignancy. All 5 patients were males with known crocidolite asbestos exposure, who had received no treatment for their disease and in whom the diagnosis was confirmed by cytology, histology and electron microscopy (EM). These lines have been in culture from 11 to 25 months, and all of them for more than 18 passages. The appearance of the cells in culture was extremely varied; in 3 of the lines they were spindle-shaped with few vacuoles (JU77, LO68 and ONE58); in 1 line they had a thick, stellate shape with vacuoles (NO36) and in 1 they were very pleomorphic in both shape and size with irregular membranes and numerous vacuoles [DeH128 (M)]. Upon reaching confluence, cells in 3 of the 5 lines assumed the cobblestone-like pattern characteristic of epithelial-type cells, whereas in the other 2 (LO68 and ONE58) they remained spindle-shaped. All 5 lines demonstrated a loss of contact inhibition (i.e., piling) at confluence. Minimum doubling times varied significantly from 18 hr (JU77) to more than 30 hr [DeH128 (M)]. Cytological examination showed characteristic mesothelial/mesothelioma morphology, and epithelial membrane antigen (EMA) and cytokeratin were demonstrated in cells from all 5 lines. These cells lacked CEA and epithelial mucin. The presence of cell junctions, glycogen and numerous long, thin, branching microvilli was readily demonstrable by EM. All lines had abnormal karyotypes, with the modal chromosome number varying from 40 to 80. Variable chromosome numbers, numerous structural rearrangements and unrecognizable marker chromosomes were readily observed; however, the only consistent change seen was del 6q21 in 4 of the 5 lines. The establishment of these 5 cultured human MM cell lines now provides an opportunity for comparative study of several aspects of the biology of MM in vitro as well as screening new treatment modalities.

Adult↗
PubMed1991

Interaction of spatial frequency and separation in vernier acuity.

There are two general theories which attempt to explain the ability to judge the relative positions of objects in the visual field. The first is the "local-sign" model which assigns location to individual features of the stimulus. The other is the "channel" model involving pooling of responses of overlapping filters having different spatial frequency and orientation tuning. We set out to investigate these using vernier stimuli whose frequency content could be controlled. The stimuli consisted of vertically orientated sinusoidal gratings placed one above the other with a variable separation between them. Thresholds for high frequency gratings increased rapidly with separation while low frequencies were little affected. In addition the cycle width of gratings which could just be distinguished as being in or out of phase and of gratings which gave optimum vernier acuity both increased linearly with separation. Results are discussed in terms of a model based on spatial frequency filters and we suggest that our findings place significant constraints upon a local-sign model.

Contrast Sensitivity↗
PubMed1991

The use of monoclonal antibody 44-3A6 in cell blocks in the diagnosis of lung carcinoma, carcinomas metastatic to lung and pleura, and pleural malignant mesothelioma.

Monoclonal antibody (MoAb) 44-3A6 recognizes a glandular differentiation-associated antigen and has been used to identify exocrine differentiation in pulmonary carcinomas. The authors assessed its value in the diagnosis of lung carcinomas metastatic to lung/pleura and pleural malignant mesothelioma (MM), using cell blocks derived from cytologic specimens. Sixty-three primary lung carcinomas, 31 metastatic adenocarcinomas (ACs) (from breast, gastrointestinal tract, or genitourinary tract), and 36 MMs were immunostained with 44-3A6, Leu-M1, and anti-carcinoembryonic antigen (CEA). The results confirm the value of 44-3A6 in identifying ACs but do not allow distinction between those of pulmonary, breast, GIT, or ovarian mucinous derivation. Endometrial, ovarian serous, and renal ACs are essentially nonreactive, as are almost all MMs. The occurrence of one positive MM predicates caution in interpreting 44-3A6 positivity in isolation, but, judiciously used with other discriminating antibodies such as Leu-M1 and anti-CEA, 44-3A6 is of value in the differential diagnosis of ACs and MMs. Further, its applicability to cytologic specimens may obviate the need for more invasive diagnostic procedures and lead to rapid, accurate diagnosis.

Antibodies, Monoclonal↗
PubMed1991

Factors affecting light scatter in contact lens wearers.

We measured forward light scatter at 3.5, 10, and 28 degrees using a portable stray light meter. Subjects included 66 normal subjects (age range 19 to 79 years), 17 established hydrophilic contact lens wearers, and 15 rigid gas permeable (RGP) contact lens wearers. Contact lens deposits were measured using a modified Rudko procedure and a Leitz/Wild Makroscope M240. Corneal health was assessed using slitlamp biomicroscopy. Results showed a significant increase in light scatter with age, particularly after the age of 40 years. Stray light scores were significantly lower in pigmented non-Caucasian subjects, particularly at larger angles. The stray light scores were significantly greater in contact lens wearers than in age-matched normals, but were not found to correlate with the amount of lens deposits. Scores from hydrophilic lens wearers after removal of their lenses were significantly higher than results from RGP wearers after removal of their lenses and from age-matched normals. This suggests the presence of subclinical corneal edema in some of these subjects.

Adult↗
PubMed1991

Extracellular localization of human connective tissue mast cell granule contents.

In early phases of cutaneous inflammation, connective tissue mast cell degranulation is associated with apparent secretion and externalization of immunoreactive chymotryptic serine proteinase. To determine whether this event is associated with structural evidence of granule externalization, we studied the sequential evolution of IgE-mediated hypersensitivity in vivo, as well as mast cell degranulation provoked by a variety of stimuli in cultured explants of human skin. By 1 min after intradermal antigen challenge with ragweed extract, mast cell degranulation was associated with apparent extrusion of intragranule constituents into the pericellular connective tissue. Similar features typified cultured skin explants exposed for 45 min to anti-IgE and other mast cell secretagogues (morphine sulfate, calcium ionophore A23187, compound 48/80, and substance P). Once externalized, granule constituents could be identified within the dermal matrix by their rounded contour and structural similarity to solubilized granule matrices remaining within actively secreting cells. These data indicate that externalization of connective tissue mast cell granule contents occurs early after secretagogue exposure, potentially accounting for infrequent documentation of this event in naturally occurring dermatoses. The ability to recognize externalized granule products at a morphologic level should facilitate the understanding of interactions between mast cell-derived mediators and target structures of the dermal microvasculature.

Adult↗
PubMed1991

Miliary spread of malignant pleural mesothelioma without a clinically identifiable pleural tumour.

A 44-year-old man with past minor exposure to blue asbestos presented with supraclavicular lymphadenopathy and miliary shadowing on his chest radiograph. Cytology and electronmicroscopy on material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. Malignant mesothelioma cells were also present in bronchoalveolar lavage fluid and on transbronchial lung biopsy. At autopsy the right pleural cavity was studded with small tumour nodules. This case demonstrates that malignant mesothelioma may present as metastatic disease and without evidence on conventional investigations of a primary pleural tumour.

Adult↗
PubMed1991

Cytotoxic folliculitis in GvHD. Evidence of follicular stem cell injury and recovery.

Recent observations indicate that stem cells of the murine hair follicle exist exclusively as a subpopulation of relatively undifferentiated outer root sheath cells located in the bulge region at the mid-portion of the follicle. Because it has been hypothesized that stem cells of interfollicular epidermis may represent targets of cytotoxic responses in acute graft-versus-host disease (AGVHD), we studied murine AGVHD and observed sequential skin biopsies for the presence and evolutionary pattern of follicular injury. Highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence in skin of AGVHD, which peaked three weeks post-transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease, which peaked during the fourth week post-transplant. Analysis of skin from both strain/effector cell combinations revealed follicular infiltrates preferentially involving follicular stem cell (FSC) regions (bulge) of anagen follicles between the second and third weeks post-transplant. These infiltrates often preceded infiltration of adjacent interfollicular epidermis and were associated with follicular involution to telogen (resting) phase. By the fourth week post-transplant, greater than 50% of follicles were in telogen phase and residual inflammation was minimal. This provided a unique opportunity to observe follicular recovery from telogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Skin cancer: diagnosis and management.

Patients should be encouraged to adopt sun protective habits and have new or changing skin lesions evaluated promptly. Physicians should thoroughly examine all of the skin and be prepared to assess individual risks for skin cancer. When the issue is in doubt, skin biopsy or a more detailed examination by a skin specialist is recommended. Educational campaigns directed toward prevention and early detection of skin cancer can greatly reduce the morbidity and mortality of this very common disease.

Biopsy↗
PubMed1991

Characterization of target injury of murine acute graft-versus-host disease directed to multiple minor histocompatibility antigens elicited by either CD4+ or CD8+ effector cells.

The precise identity of effector mononuclear cells capable of eliciting acute graft-versus-host disease (AGVHD) is controversial. In this study, highly purified subsets of donor T cells were used to produce AGVHD to multiple minor histocompatibility (H) antigens in two strain combinations of mice matched for the major histocompatibility complex (MHC). In the C3H.SW- greater than B6 strain combination, only CD8+ effector cells produced histologic evidence of AGVHD in skin and liver, which peaked 3 weeks after transplant. In the B10.D2- greater than DBA/2 strain combination, CD4+ effector cells, and to a lesser extent, CD8+ cells, mediated disease in skin, liver, and intestine, which peaked during the fourth week after transplant. Analysis of skin and liver from both combinations showed target cell injury that was phenotypically similar and resembled that previously described in human disease in other studies. In addition, prominent epithelial injury also was detected in oropharyngeal mucosa, esophagus, hepatobiliary ducts, and seminal vesicle in both transplant settings. These findings indicate that functionally different subsets of donor T cells may be capable of initiating common pathways of cellular injury in selected target sites in AGVHD, and have potential implications for strategies that seek to ablate disease development by manipulation of donor marrow before transplantation.

Acute Disease↗