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Biomedical subjects

D Whitaker

Publications and source records attributed to D Whitaker.

At least 109 records · Page 6Linked to original sources

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↗

Spatial summation determines the contrast response of displacement threshold hyperacuity.

The effect of line length on displacement threshold hyperacuity at various levels of contrast was investigated. At high contrasts there was no significant effect of line length, but as contrast was reduced thresholds for shorter line lengths increased rapidly. Thresholds at longer line lengths demonstrated a form of contrast saturation which differed from vernier acuity whose thresholds increased consistently with a reduction in contrast. As line length in the displacement threshold task was reduced, the amount of contrast saturation became less and displacement thresholds therefore resembled the contrast response of vernier acuity. Results are explained in terms of spatial summation along the length of the lines, the effects of which depend upon the spatial configuration of the hyperacuity stimulus under consideration.

Contrast Sensitivity↗

Time trends in the prevalence of human papillomavirus infections in archival Papanicolaou smears: analysis by cytology, DNA hybridization, and polymerase chain reaction.

A retrospective study was undertaken to determine the prevalence of human papillomavirus (HPV) infections in routine Papanicolaou (Pap) smears collected by general practitioners from Western Australian women in each of the years 1972, 1982, and 1987. HPV infection was detected by cytology, dot-blot hybridization, or polymerase chain reaction (PCR). It was found that the prevalence of HPV infection remained unchanged over the 15 year study period, was independent of age, and was associated with normal cytology at a rate far greater than previously recognized. Indeed, the prevalence of cervical intraepithelial neoplasia (CIN) lesions, as detected by cytology, was 3.0% in 1972 and 3.8% in 1982 and 1987. The prevalence of HPV infection, detected as koilocytosis or parakeratosis, was 6.5%, 6.8%, and 5.3% in smears collected in 1972, 1982, and 1987, respectively, from 1,800 women. In 237 cytologically normal smears reprocessed for HPV-DNA studies, the prevalence of HPV 16 was determined to be 15.6%, 11.2%, and 17.8% in 1972, 1982, and 1987, respectively, as determined by dot-blot hybridization. However, the PCR detected HPV 16 in an additional 55.5%, 62.9%, and 57.0% of cytologically normal and dot-blot negative smears. The prevalence of HPV 16 infection in cytologically normal smears was estimated to be 71.0%, 74.1%, and 74.8% in 1972, 1982, and 1987, respectively, by combining the HPV 16 dot-blot and PCR-positive results. The high prevalence of HPV 16 in cytologically normal Pap smears suggests that infection with HPV 16, as detected by PCR amplification, does not place women in a high-risk category for cervical cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Displacement thresholds for various types of movement: effect of spatial and temporal reference proximity.

Displacement thresholds for unidirectional stop-go-stop and continuous types of movement were measured as a function of duration of movement. A circular stationary reference of varying radius surrounding the stimulus was either present throughout the whole duration of movement, disappeared just before movement began, or was totally absent. In the absence of the reference, thresholds increased with duration according to a constant velocity prediction. When present continuously, thresholds for all durations of movement were reduced. For references of close proximity, displacement thresholds became independent of movement duration. Results are discussed in terms of direct mechanisms of movement detection and also spatio-temporal hyperacuity analysis mediating the detection of relative positional change.

Humans↗

Neural contribution to spatiotemporal contrast sensitivity decline in healthy ageing eyes.

Contrast sensitivity thresholds were measured over a range of spatial and temporal frequencies in both a group of young and older observers. Results demonstrate a significant reduction in contrast sensitivity of the older age group at all but the lowest combinations of spatial and temporal frequencies investigated. The senile miosis and reduced optical transmission of the older eye was then mimicked using the younger observers as subjects. This combined effect of reducing retinal illumination produced no significant change in sensitivity. These findings are discussed in terms of neural loss within the visual pathways with increasing age.

Adult↗

Differences in the legibility of letters at contrast threshold using the Pelli-Robson chart.

One disadvantage of using high-contrast letters as test objects when measuring visual acuity is the fact that they are not of equal legibility. A number of charts are now commercially available that assess contrast sensitivity using letter targets. This study attempted to assess the legibility of letters at contrast threshold on the Pelli-Robson letter contrast sensitivity chart by determining the percentage of correct responses for each of the ten Sloan letters at contrast threshold. Results of 493 contrast sensitivity measurements taken in optometric practice indicated that there is a definite difference in legibility between letters at contrast threshold as for letters at acuity threshold. The data suggest that the probability of correctly identifying two out of a group of three letters at threshold on the Pelli-Robson chart varies between 67% and 97% due to letter type alone. Because of the very regular and pronounced miscalling of the letter C as an O, we suggest that this should be accepted as a correct call during threshold measurements on the Pelli-Robson chart. This helps to balance the legibility of different groups of letters.

Contrast Sensitivity↗

An unusual presentation of a congenital benign apocrine hamartoma.

A case of an unusual benign apocrine hamartoma was studied by light microscopic, immunohistochemical, and electron microscopic methods. This tumor clinically showed a linear configuration and was located on the midline chest of a pubescent male. Microscopic studies revealed features of both a tubular apocrine adenoma and a syringocystadenoma papilliferum.

Biopsy↗

Phenotypes and interactions of human melanocytes and keratinocytes in an epidermal reconstruction model.

The morphologic and antigenic phenotype of normal human melanocytes and keratinocytes was investigated in monolayer and 3-dimensional cultures in an effort to develop an epidermal model that resembles the normal human epidermis. When cultured for several passages in optimal growth medium, pure cultures of either cell type could be established as demonstrated by light and electron microscopy and with monoclonal antibodies defining melanocyte- and keratinocyte-associated antigens. Three-dimensional growth of keratinocytes on polycarbonate filters was induced by increasing calcium concentrations in the culture medium and exposing cultures to air. After 30 to 35 days incubation, the 3-dimensional keratinocyte cultures reached a total of 12 to 25 layers and keratinocytes of various stages of differentiation formed three morphologically and antigenically different strata. The basal layer of these constructs consisted of ovoid cells with desmosomes and hemidesmosome-like structures. These cells expressed low molecular weight cytokeratins similar to basal cells in situ. The intermediate layer, representing the stratum spinosum in situ, contained flat cells with keratohyaline granules and many desmosomes. These cells expressed gp 80 kilodaltons, gp 40 to 50 kilodaltons, involucrin, and filaggrin. The upper layer, the stratum corneum equivalent, contained large, flattened cells with keratohyaline granules. The majority of these cells were anucleate. When melanocytes were cocultured with keratinocytes in monolayer or in epidermal reconstructs, they assumed a multidendritic morphology and donated pigment to surrounding keratinocytes. The majority of pigmented cells localized singly within the basal layer of the reconstructs and their dendrites were intimately associated with keratinocyte plasma membranes. Pigment donation to keratinocytes appeared to occur through the uptake of melanosome-containing dendrite fragments and phagocytosis of individual melanosomes by keratinocytes. It is hypothesized that keratinocytes produce unique microenvironmental factors that regulate the melanocytic phenotype.

Cell Communication↗

Nine-year survival in a case of untreated peritoneal mesothelioma.

A patient with malignant mesothelioma of the peritoneum, which has been untreated except for regular paracentesis for effusions, has remained alive and generally-well for nine years. The poor prognosis that usually is ascribed to this disease may not be applicable universally.

Aged↗

The systemic administration of gamma interferon inhibits collagen synthesis and acute inflammation in a murine skin wounding model.

The ability of gamma interferon (IFN-gamma) to affect cutaneous collagen synthesis in vivo was examined in a murine wounding model. Reproducible areas of full-thickness skin necrosis were produced by argon laser radiation. Mice received recombinant murine IFN-gamma (rMuIFN-gamma) (8.7 X 10(3) units/hr) over 14 d via osmotic pumps implanted subcutaneously or intraperitoneally. At 14 and 21 d after wounding, there was less fibrous tissue in healing scars of treated animals as determined by light and transmission electron microscopy. Associated with the decrease in connective tissue was an increase in the acid mucopolysaccharide content of healing scars, which was largely hyaluronate. Quantitative image analysis of electron micrographs confirmed that less collagen was present in healing scars of animals receiving rMuIFN-gamma. The mean cross-sectional area of collagen fibers was smaller in specimens from treated mice, but no difference was seen in the size of collagen fibrils. The time required to obtain full skin closure was also delayed 23%-27% in treated animals. Using this injury model, we also found that rMuIFN-gamma significantly reduced the degree of perilesional erythema surrounding the laser injury sites and, in the first 6 d after wounding, the degree of polymorphonuclear infiltrate present histologically at lesional sites. Indeed, rMuIFN-gamma also decreased the cutaneous accumulation of neutrophils induced by known proinflammatory mediators, such as interleukin 1 and activated serum. Thus, systemically administered IFN-gamma not only down-regulates collagen synthesis in the skin but also modulates in a previously unrecognized manner: neutrophil accumulation at sites of tissue injury in vivo.

Acute Disease↗

Intercellular adhesion molecule expression in the evolving human cutaneous delayed hypersensitivity reaction.

Intercellular adhesion molecule-1 (ICAM-1), putatively expressed by antigen-presenting or target skin cells, is a ligand for the lymphocyte function-associated antigen (LFA-1) present on circulating lymphocytes. Immunohistochemistry of normal adult human skin using monoclonal antiserum to ICAM-1 demonstrated focal reactivity restricted to endothelium lining the dermal microvasculature. Delayed hypersensitivity responses elicited with dinitrochlorobenzene in the skin of the same subject were evaluated sequentially over a 96 h period using immunohistochemical and ultrastructural techniques. The first alteration observed consisted of mast cell degranulation within perivenular foci in the superficial dermis at 4 h after antigen challenge. Sparse superficial perivascular T-cell infiltrates were present by 24 h. Progressive staining for ICAM-1 was observed in microvascular endothelium and in dermal dendritic cells between 24 and 48 h. ICAM-1 expression was documented focally within the lower epidermis at 48 h and diffusely within the lower and upper epidermal layers at 96 h. ICAM-1 expression by keratinocytes was consistently associated with T-cell migration into the epidermis, whereas migration was never observed in the absence of ICAM-1 reactivity. Immunoelectron microscopy confirmed ICAM-1 to be exclusively present on endothelial cells, dermal dendritic cells, mononuclear cells, and keratinocytes, and permitted characterization of the patterns of membrane reactivity. ICAM-1 expression by epidermal cells appears to be closely linked to the progressive migration of T cells from the dermis into the epidermis that characterizes cutaneous delayed hypersensitivity.

CD4-Positive T-Lymphocytes↗

Ultrastructural changes in red blood cells following pulsed irradiation in vitro.

The careful choice of a combination of laser parameters such as wavelength, pulse duration, and dose has provided a means for confining laser energy to specific targets within tissue such as oxyhemoglobin within the cutaneous microvasculature. In the process of achieving such vascular selectivity, certain ultrastructural changes in red blood cell (RBC) cytoplasm have been observed, such as the generation of intracytoplasmic electron-lucent spherical structures. These structures, ranging in size from 80 to 1000A, were seen in RBCs exposed to laser doses at and above threshold, and appeared to represent a morphologically novel form of highly-specific tissue injury. This in vitro study using RBC in phosphate buffered saline (PBS) was undertaken to better understand the mechanism(s) that could have been responsible for these unique morphologic changes. We conclude that the intracytoplasmic electron-lucent spherical structures seen within RBCs were heat-fixed molds formed around vaporized water bubbles and were not produced by the release of oxygen from the oxyhemoglobin moiety during 577-nm laser irradiation.

Erythrocytes↗

The subjective assessment of cataract.

The medical treatment of cataract now appears to be a distinct possibility. A number of anti-cataract formulations are being clinically tested, and more clinical trials are being planned. To obtain a true assessment of a drug's efficacy, a battery of tests are needed which can accurately assess cataract progress. A clinical trial of the proposed anti-cataract drug Bendalina is being conducted. The six subjective methods used to assess cataract progression in the trial are presented. These are refractive error, LogMAR visual acuity, contrast sensitivity, glare sensitivity, retinal visual acuity and displacement threshold hyperacuity. The reasons for using each technique and their method of measurement is explained.

Aged↗

Prediction of visual function behind cataract using displacement threshold hyperacuity.

Visual acuity and displacement threshold hyperacuity were measured in a group of patients awaiting cataract extraction, and this was repeated several weeks subsequent to surgery. In addition, measurements were made on a group of patients with various ocular pathologies but without the presence of cataract. Displacement thresholds in the cataract group increased only slightly with the severity of the opacity. On the other hand, displacement thresholds for the pathology group showed a marked dependence upon visual acuity--the worse the acuity, the higher the threshold. This results in a clear distinction between vision loss due to optical factors (cataract) and retinal/neural factors. There was a good correlation between pre- and post-operative displacement thresholds in the cataract group, with post-operative thresholds being slightly better than pre-operative thresholds. The results suggest that this technique may offer patients a good indication of the likely quality of vision achieved following cataract extraction.

Aged↗

Contrast sensitivity and glare sensitivity changes with three types of cataract morphology: are these techniques necessary in a clinical evaluation of cataract?

LogMAR visual acuity, contrast sensitivity and glare sensitivity measurements were made on 39 eyes of 18 cataractous subjects and compared against normative data. Only cataracts of one of the main three morphological cataract types were used--cortical, nuclear and posterior subcapsular. Results indicate that contrast sensitivity decline with cataract is an intermediate and high spatial frequency loss. For nuclear and cortical cataracts with a LogMAR visual acuity of less than 0.5 (Snellen equivalent better than 6/18), there was no loss of contrast sensitivity at the lowest spatial frequency (1 c/deg). For posterior subcapsular cataracts, low spatial frequency contrast sensitivity loss did occur but was unrelated to visual acuity. Glare sensitivity increased for all cataract types. This was related to visual acuity for both cortical and nuclear cataracts but was not for the posterior subcapsular type. It was concluded that contrast and glare sensitivity measurements are a useful part of the assessment of visual function in patients with posterior subcapsular cataract.

Aged↗

Centroid evaluation in the vernier alignment of random dot clusters.

Clusters of random dots have an advantage over the line elements of a typical vernier acuity task in that their internal light distributions may be easily manipulated without affecting the location of their boundaries. The ability of observers to detect the vertical misalignment of two clusters of random dots was measured over a range of cluster sizes and number of constituent dots. Provided the resultant dot density is high enough to allow interpolation to occur, results demonstrate that the task is performed by analysing the centroid (centre of gravity) of the clusters along the direction of their offset.

Form Perception↗

Pulsed dye laser (577 nm) treatment of portwine stains: ultrastructural evidence of neovascularization and mast cell degranulation in healed lesions.

Portwine stains were examined before, immediately after, and 1 yr after successful clearance by a pulsed dye laser (577 nm) using ultrastructural techniques. Dilated vascular channels and mast cell hypoplasia characterized lesional skin before treatment. Immediately after treatment, widespread selective vessel necrosis, similar to changes previously described, was observed. One year after laser irradiation, the abnormally ectatic portwine stain vessels had been replaced by small venules and arterioles, similar in number and diameter to blood vessels in normal skin; the only difference noted was that these new vessels were surrounded by easily identifiable mast cells. Many of these mast cells exhibited evidence of activation and degranulation. We conclude that mast cells may play an important role in the neovascularization of portwine stains treated by 577-nm dye laser irradiation.

Adolescent↗