Biomedical subjects

D Whitaker

Publications and source records attributed to D Whitaker.

At least 73 records · Page 4Linked to original sources

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1989

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↗

PubMed1988

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↗

PubMed1988

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↗

PubMed1988

Ultrastructure and dynamics of selective mitochondrial injury in carcinoma cells after doxycycline photosensitization in vitro.

Mechanisms and intracellular sites of photosensitized damage were investigated in cultured MGH-U1 cells treated with doxycycline (DOTC). Cells were examined by phase-contrast, fluorescence, and electron microscopy at various times (15 minutes to 24 hours) after ultraviolet irradiation (320-400 nm). DOTC localized selectively within the mitochondria, as shown by colocalized fluorescence with rhodamine 123 (R123). Photosensitization at 1 J/sq cm caused striking swelling of the mitochondrial matrix and disruption of the cristae, accompanied by loss of the ability of mitochondria to concentrate R123. These changes progressed during the first hour after irradiation, and then were followed by partial recovery of mitochondrial ultrastructure and function. At no time were other organelles seen to be affected. It appears that this selective, photosensitized alteration was a consequence of localized and partially reversible damage to the mitochondrial inner membrane. In contrast, exposure to 2-6 J/sq cm caused irreversible injury and necrosis.

Doxycycline↗

PubMed1987

Epidermal cells in activation of suppressor lymphocytes: further characterization.

Intravenous administration of hapten-coupled, high-density (density greater than 1.077) epidermal cells (HD-EC) to mice results in the appearance of transferable splenic T suppressor (Ts) cells as assayed in adoptive transfer experiments. Depletion of I-A bearing cells from the HD-EC population before hapten coupling prevents these cells from inducing Ts cell formation, whereas depletion of Thy-1-bearing cells from the HD-EC cell preparation has no effect. When HD-EC are adhered to glass for 2 hr, the ability to induce Ts cell formation resides in the adherent population. Exposure of HD-EC to a dose of ultraviolet radiation (UVR) that largely abrogates the ability of hapten-coupled EC to immunize mice for a DTH response does not affect the ability of these cells to activate Ts cells. Treatment of mice with i.p. administration of 20 mg/kg of cyclophosphamide 2 days before EC harvesting abrogates the ability of HD-EC from these mice to induce Ts cell formation. HD-EC from B10.A(3R) (I-Jb) but not B10.A(5R) (I-Jk) mice induce Ts cell formation in B10.A(3R) mice, demonstrating that the ability to do so is restricted by the I-J locus. Transmission electron microscopy of adherent HD-EC populations demonstrated that two cell types were present. One type had the characteristics of keratinocytes; the other was monocyte-like and resembled Langerhans cells or indeterminate cells in many aspects. Immunoelectron microscopy revealed this second cell type to bear I-A/I-E antigen. These cells were T-200 positive and Mac-1 negative by immunoperoxidase staining. Extensive examination by light and electron microscopy failed to reveal any dermal components in the EC populations; however, a very small degree of dermal contamination cannot be excluded. Thus, EC that activate afferent-acting Ts cells are high-density, I-A+, Thy-1-, I-J restricted, glass adherent, and functionally UVR resistant and cyclophosphamide sensitive.

Animals↗

PubMed1987

Detection of anticentromere antibodies using cloned autoantigen CENP-B.

A solid-phase enzyme-linked immunosorbent assay has been established using a cloned fusion protein, CtermCENP-B [beta-gal], as antigen. The fusion protein carries the major epitope of CENP-B, the major centromeric autoantigen. The enzyme-linked immunosorbent assay was more sensitive than immunofluorescence techniques in detecting anticentromere antibodies in patients with scleroderma or Raynaud's disease, and was weakly positive in 3% of normal controls and in 3% of 70 patients with other connective tissue diseases.

Adult↗

PubMed1987

Role of macrophages in mesothelial healing.

The role of macrophages in rat mesothelial healing was evaluated in vivo and in vitro. In animals whose circulating monocytes were severely depressed, the healing rate was retarded; however, this effect was partly reversed by the introduction of macrophages into the injured site, suggesting that macrophages are of fundamental importance in the healing of mesothelial wounds. Furthermore, it was found that wound exudates stimulated DNA synthesis in normal quiescent mesothelial cells and the component principally responsible for this activity was the macrophage. Cultured macrophage-conditioned media also induced an increase in mesothelial replication. Moreover, the mitogenic activity present in both wound exudates and macrophage-conditioned media was increased by dialysis and diminished by heating at 80 degrees C for 1 h. The putative mesothelial mitogenic factor in the supernatant of wound exudates and macrophage cell cultures has a molecular size greater than 7000 dalton and is stable after mild heating (60 degrees C, 1 h). It is postulated that exudate macrophages secrete mitogenic factor(s) which stimulate mesothelial proliferation, and initiate healing.

Animals↗

PubMed1987

Melanosomes are a primary target of Q-switched ruby laser irradiation in guinea pig skin.

The specific targeting of melanosomes may allow for laser therapy of pigmented cutaneous lesions. The mechanism of selective destruction of pigmented cells by various lasers, however, has not been fully clarified. Black, brown, and albino guinea pigs were exposed to optical pulses at various radiant exposure doses from a Q-switched, 40 nsec, 694 nm ruby laser. Biopsies were analyzed by light and electron microscopy (EM). Albino animals failed to develop clinical or microscopic evidence of cutaneous injury after irradiation. In both black and brown animals, the clinical threshold for gross change was 0.4 J/cm2, which produced an ash-white spot. By light microscopy, alterations appeared at 0.3 J/cm2 and included separation at the dermoepidermal junction, and the formation of vacuolated epidermal cells with a peripheral cytoplasmic condensation of pigment. By EM, enlarged melanosomes with a central lucent zone were observed within affected epidermal cells at 0.3 J/cm2. At 0.8 and 1.2 J/cm2, individual melanosomes were more intensely damaged and disruption of melanosomes deep in the hair papillae was observed. Dermal-epidermal blisters were formed precisely at the lamina lucida, leaving basal cell membranes and hemidesmosomes intact. Possible mechanisms for melanosomal injury are discussed. These observations show that the effects of the Q-switched ruby laser are melanin-specific and melanin-dependent, and may be useful in the selective destruction of pigmented as well as superficial cutaneous lesions.

Animals↗

PubMed1987

Oscillatory movement displacement thresholds: resistance to optical image degradation.

Vernier acuity, under optimal conditions, appears remarkably resistant to image degradation. This characteristic has been used to assess neural function in cataract patients who exhibit poor spatial resolution. Conventional resolution tests fail to differentiate between neural and optical causes of visual loss. The oscillatory movement displacement threshold--the smallest amplitude of oscillation which gives rise to the perception of movement--provides an alternative hyperacuity test. This may offer advantages over vernier acuity. The effect of image defocus upon displacement thresholds for a sinusoidal contrast grating of spatial frequency 2 c deg-1 was investigated for high (15 Hz) and low (2 Hz) oscillation frequencies. With visible stationary references, subjects were more sensitive to oscillation frequencies of 2 Hz than to 15 Hz (F 1,9 = 33.34, p less than 0.005) whilst blur of up to 2 dioptres had no significant effect (F3,27 = 1.73, p greater than 0.1). Simulating media opacities by spatial degradation affected both grating acuity and contrast sensitivity functions, whilst displacement thresholds remained largely unaffected. Results suggest that oscillatory movement displacement thresholds may be of value in assessing ocular neural dysfunction in the presence of media opacities.

Cataract↗

PubMed1987

Movement in decline? Oscillatory movement displacement thresholds increase with ageing.

Displacement thresholds for continuous oscillatory movement were determined for ten subjects in each of three age groups--20-23, 40-55 and 60-80 years. Oscillation frequencies of 1, 2, 3, 5, 8, 13 and 20 Hz were used, all subjects having a corrected visual acuity of 6/5. A randomized block factorial design of analysis of variance revealed significant effects of both temporal frequency of oscillation (F6,189 = 4.10, p less than 0.001) and age (F2,189 = 46.98, p much less than 0.001). The deterioration in movement sensitivity occurs equally at both high and low temporal frequencies--no significant interaction effects being revealed (F12,189 = 0.45, p = not significant). The frequency effects are ascribed to underlying mechanisms mediating movement perception. Reasons for decreased movement sensitivity with increasing age are discussed.

Adult↗

PubMed1987

Theory and evidence for a clinical hyperacuity test.

An accurate assessment of the integrity of the visual system behind opaque ocular media is of vital clinical significance, especially with regard to surgical intervention. Several techniques which are currently available to assist in this task are considered with regard to their value. Theoretical considerations indicate that hyperacuities, by virtue of their resistance to optical image degradation, should constitute ideal candidates to perform the above evaluation. Hyperacuity studies involving cataract simulation support this view, as does the clinical data which is presently available. Further work should reveal an optimum hyperacuity configuration or a battery of hyperacuity tests and establish their clinical merit.

Humans↗

PubMed1986

Alveolitis of pulmonary asbestosis. Bronchoalveolar lavage studies in crocidolite- and chrysotile-exposed individuals.

Bronchoalveolar lavage (BAL) findings in 27 individuals with crocidolite- or chrysotile-induced asbestosis were compared to BAL findings in 29 unexposed control subjects. Alveolitis, defined as an increase in the proportions and/or absolute numbers of inflammatory cells present in BAL fluid compared to values in control subjects, was present in 26 (96 percent) subjects with asbestosis. Most exhibited a neutrophil-eosinophil alveolitis, with neutrophil proportions increased to 7.4 +/- 0.7 percent and eosinophil proportions increased to 2.2 +/- 0.4 percent, compared to 2 +/- 0.5 percent and 0.4 +/- 0.01 percent, respectively, in control subjects (p less than 0.01 for both neutrophils and eosinophils). An increase in the total number of neutrophils and eosinophils per ml of lavage fluid was also seen (neutrophils 23 +/- 5 and eosinophils 13 +/- 4 per ml; p less than 0.05 compared to control subjects). Severity of the alveolitis, defined by the neutrophil or eosinophil proportions, was independent of a history of exposure to cigarette smoke. The pattern and severity of alveolitis in crocidolite- and chrysotile-induced asbestosis were similar. There was a significant correlation between duration of exposure to asbestos and neutrophil proportions (p less than 0.01). No significant difference in the severity of the alveolitis was observed between individuals with radiologic and physiologic evidence of asbestosis compared to those with asbestos exposure and crackles alone, suggesting that, in asbestosis as in other chronic interstitial lung diseases, radiologic and physiologic parameters do not reflect the severity of the alveolitis. This study demonstrates that a neutrophil-eosinophil alveolitis is present in individuals with crocidolite- and chrysotile-induced asbestosis, that this alveolitis is independent of cigarette smoking, and that the severity of the BAL changes is not reflected in radiologic and physiologic changes.

Asbestos↗

PubMed1986

Pleural fluid CEA levels in the diagnosis of malignant mesothelioma.

A study was undertaken to investigate whether the levels of carcino-embryonic antigen (CEA) in serous effusions helped distinguish between primary mesothelioma and metastatic adenocarcinoma in a body cavity. The investigation was designed to assess the role of the assay only when cytological analysis of the fluid had already shown the presence of malignant cells. No case of mesothelioma studied had levels of CEA above 2.9 ng/ml, whereas 67% of the adenocarcinomas tested were above 15 ng/ml. The test is helpful, therefore, in differentiating between these two types of malignant effusions.

Adenocarcinoma↗

PubMed1986

Displacement thresholds for continuous oscillatory movement: the effect of oscillation waveform and temporal frequency.

Displacement thresholds for continuous oscillatory movement of a grating, subtending 2 cycle deg-1, were measured for square-, triangular- and sine-wave oscillation over the frequency range 1-20 Hz. Without reference lines, thresholds were highly dependent upon temporal frequency and oscillation waveform. With reference lines, thresholds were dependent upon oscillation waveform but not frequency. Greatest sensitivity was shown to square-wave oscillation and least to triangular-wave. Results are discussed in terms of velocity- and displacement-analysing systems. Increasing the spatial frequency of the sinusoidally oscillating grating had little effect on displacement thresholds.

Humans↗