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Biomedical subjects

D Whitaker

Publications and source records attributed to D Whitaker.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗