Biomedical subjects

D Whitaker

Publications and source records attributed to D Whitaker.

At least 127 records · Page 7Linked to original sources

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 One year after laser irradiation, the abnormally ectatic portwine stain vessels had been replaced by small venules and arterioles, similar in number and diameter to blood vessels in normal skin; the only difference noted was that these new vessels were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↗

PubMed1985

Mesothelial healing: morphological and kinetic investigations.

By using structural, kinetic and irradiation techniques it is possible to show that mesothelial healing is a local event. Initially, macrophages occupy the surface of a wound on the injured visceral layer, while mesothelial proliferation proceeds at the edge of the wound and the opposing parietal surface. Fibrin is formed on the wound surface within 24 h, even in the absence of much haemorrhage. Mesothelial ingrowth begins with isolated cells migrating from the wound edge as well as from the serosal surface apposing the wound where mesothelial cells are actively replicating. The cells presumably slide over a bridge of fibrin and macrophages, a process likely to be enhanced by the serosal fluid. Early colonization by macrophages results in the removal of debris and probably prevents the formation of adhesions during mesothelial restoration.

Animals↗

PubMed1985

The influence of luminance on displacement thresholds for continuous oscillatory movement.

Displacement thresholds were determined for a sinusoidally-modulated contrast grating, having a spatial frequency of 2 c/deg, whose mean luminance could be varied. The grating underwent continuous oscillatory simple harmonic motion. Displacement thresholds were determined for frequencies of 1, 3, 5, 7 and 10 Hz using the method of limits for each mean grating luminance of 3.8, 8.9, 26, 62 and 134 cd/m2. With low oscillation frequencies a marked reduction in sensitivity is produced by reducing the mean luminance of the grating. This is not the case with higher oscillation frequencies when mean luminance has little effect upon sensitivity.

Eye Movements↗

PubMed1985

Vulvar lymphangioma circumscriptum: a rare complication of therapy for squamous cell carcinoma of the cervix.

The clinical and pathological features of a case of multifocal lymphangioma circumscriptum of the vulva are reported in a patient with chronic lymphedema of a lower extremity. Ten years previously the patient had been treated for squamous cell carcinoma of the cervix. Although lymphangioma circumscriptum is an extremely rare complication of altered lymphatic drainage, the presence of multiple noninflammatory vesicular appearing lesions in this setting should suggest the correct diagnosis.

Carcinoma, Squamous Cell↗

PubMed1984

Diagnosis of pleural malignant mesothelioma in life--a practical approach.

This review documents a practical approach to the pathological diagnosis of pleural malignant mesothelioma based on the closed needle biopsy and effusion cytology, thus avoiding the need to resort to open surgery. Tissue diagnosis is often difficult, and the pathologist's opinion may be influenced by a consideration of three factors: the clinical setting; the adequacy and availability of specimens; and the criteria for assessment and interpretation of these. The level of confidence with which a tissue diagnosis of mesothelioma can be established using limited material depends on there being an appropriate clinical background including a history of asbestos exposure. Without this, the diagnosis should be a qualified or tentative one. For an adequate tissue sample to be obtained, the closed needle biopsy procedure is best performed by an experienced operator. All aspirated pleural effusions should be forwarded for cytological evaluation. In addition to conventional morphological studies, adequate samples permit ancillary tests to be carried out. A combined interpretive approach utilizing both histopathology and cytology is recommended in order to increase the accuracy of the diagnosis.

Adenocarcinoma↗

PubMed1983

The fine needle aspiration cytology of mediastinal lesions.

Fine needle aspiration cytology was performed in 19 mediastinal lesions. Of seven malignant neoplasms six were correctly diagnosed as malignant and in five of these accurate tumor classification was possible. Of the 12 benign lesions only four cases, all thymomas, could be diagnosed cytologically. No false-positive diagnoses of malignancy were made. The only complication of the procedure was minor pneumothorax in two patients. In five cases the use of the technique spared the patient from more invasive diagnostic procedures; in several others, valuable information was obtained prior to surgery.

Adolescent↗

PubMed1983

Failure to detect immunocytochemically reactive endogenous lectin on the cell surface of Dictyostelium discoideum.

The endogenous lectins of Dictyostelium discoideum, called discoidins I and II, have been implicated in cell cohesion during the associative phase of this organism. In an effort to repeat and extend the studies of these putative cell-surface proteins, we attempted a variety of immunocytochemical techniques. Antibodies to a mixture of the purified discoidins were raised in rabbit. Both living and fixed cells were examined by indirect immunoferritin labeling using whole antiserum and by direct immunolabeling using purified specific IgG adsorbed to colloidal gold. Cells, at the appropriate stage, of strains A3, NC-4, and WS-582 were tested. In no instance were cell surface antigens detected despite meticulous efforts to duplicate the published techniques and to extend and refine them. Specific localization was found only in the cytosol and on the cytoplasmic face of certain endomembrane vesicles, and much less so on outer nuclear and mitochondrial membranes, in inadvertently disrupted cells. In no case was specific label found on either side of the plasma membrane or on food vacuoles. Exogenously supplied discoidins, bound to cells, were successfully localized by our technique. We conclude that the discoidins are not present on the cell surface, or are there in undetectable quantities, during the associative phase. We suggest that previous demonstrations of these proteins at the cell surface were artifacts resulting from the way in which the cells were handled, which caused the binding of externalized discoidins, possibly those released from lysed cells. We believe that the current notion that the discoidins play a direct role in cell cohesion by virtue of their carbohydrate-binding capacity should be reexamined. We suggest that the true role of the discoidins is solely intracellular.

Cell Membrane↗