Synchronous vasomotion in the human cutaneous microvasculature provides evidence for central modulation.
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Adult↗
Biomedical subjects
I M Braverman
Publications and source records attributed to I M Braverman.
Topographic mapping of the cutaneous microcirculation using two outputs of laser-Doppler flowmetry: flux and the concentration of moving blood cells.
Using a "needle" probe in a template probe holder, we measured the flux and the concentration of moving red blood cell (CMBC) outputs from a Perimed (PF2B) laser-Doppler instrument at 1-mm2 contiguous sites in a 8 x 8-mm area on the flexor forearm of three subjects. Using the means of the flux and CMBC recorded at each spot, a topographic contour map was constructed for each of these parameters. Viewing the two maps together, sites with four different combinations of flux and CMBC could be identified. Trephine biopsies (2 mm) of three representative sites in each subject were performed and the upper plexus was reconstructed in 3 dimensions from serial sections. High flux/high-to-medium CMBC sites were found over the spot where the ascending arterioles entered the upper plexus. Medium flux/medium-to-low CMBC sites and low flux/medium CMBC sites were found in the peripheral part of the vascular unit that was fed by the ascending arteriole. The low flux/low CMBC sites were relatively avascular zones. Video imaging of the upper plexus in the forearm showed the same overall vascular pattern as the contour maps. The highest flux and CMBC signals were recorded when horizontally oriented vessels were present in the upper third of the plexus (400-650 microns below the stratum corneum). Topographic mapping will allow one to selectively identify different microvascular areas in the skin for physiological studies.
Adult↗
Human dermatosparaxis: a form of Ehlers-Danlos syndrome that results from failure to remove the amino-terminal propeptide of type I procollagen.
Dermatosparaxis is a recessively inherited connective-tissue disorder that results from lack of the activity of type I procollagen N-proteinase, the enzyme that removes the amino-terminal propeptides from type I procollagen. Initially identified in cattle more than 20 years ago, the disorder was subsequently characterized in sheep, cats, and dogs. Affected animals have fragile skin, lax joints, and often die prematurely because of sepsis following avulsion of portions of skin. We recently identified two children with soft, lax, and fragile skin, which, when examined by transmission electron microscopy, contained the twisted, ribbon-like collagen fibrils characteristic of dermatosparaxis. Skin extracts from one child contained collagen precursors with amino-terminal extensions. Cultured fibroblasts from both children failed to cleave the amino-terminal propeptides from the pro alpha 1(I) and pro alpha 2(I) chains in type I procollagen molecules. Extracts of normal cells cleaved to collagen, the type I procollagen synthesized by cells from both children, demonstrating that the enzyme, not the substrate, was defective. These findings distinguish dermatosparaxis from Ehlers-Danlos syndrome type VII, which results from substrate mutations that prevent proteolytic processing of type I procollagen molecules.
Amino Acids↗
Bowen's disease and internal cancer.
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Bowen's Disease↗
Contour mapping of the cutaneous microvasculature by computerized laser Doppler velocimetry.
A probe holder for laser Doppler velocimetry was designed to allow a narrow (1.24-mm) probe to be moved in increments of 1.04 mm, approximately the width of the probe window itself, so that four contiguous 1-mm2 spots in a 2.29 x 2.29 mm area could be sampled. An area as large as 2.48 x 2.48 cm can be measured with this device. The flux was fed into a computer by an analog/digital board, for visualization as a wave-form on the monitor, and for analysis by fast Fourier transforms and power spectrum analysis. Each spot sampled was given a unique x,y coordinate and the mean amplitude of the flux was designated as the z coordinate. With the aid of software, the values of these three coordinates were mathematically processed to produce contour graphs with shading that represented a map of the arteriolar circulation in the skin. This methodology allows for accurate movement and placement of the probe on the skin and the ability to relocate a spot within 1 mm of its original location after intervals of hours to days. Video images of the superficial plexus at the sites where the maps were made confirm the topographic appearance of these maps. Data generated by these maps raise the intriguing possibility that microcirculatory vessels may be engaged in a division of labor--some involved primarily with tissue perfusion, others with thermoregulation.
Computers↗
The use of immunohistologic analysis in differentiating cutaneous T-cell lymphoma from psoriasis and dermatitis.
BACKGROUND AND DESIGN: --Many investigators have applied immunohistologic analysis to skin biopsy specimens to distinguish cutaneous T-cell lymphoma (CTCL) from benign inflammatory diseases, such as psoriasis and dermatitis, which can clinically mimic early-stage CTCL. We studied the number and distribution of epidermal cells labeled with various monoclonal antibodies in normal skin and in psoriatic, dermatitic, and CTCL lesions by the immunoperoxidase technique. RESULTS: --Extensive staining of keratinocytes (KCs) with HLA-DR was seen in 27 of 41 patients with CTCL, but in only one of 14 patients with psoriasis and zero of 10 patients with dermatitis. CD2+ and CD3+ cells were present in the middle and upper epidermis of CTCL lesions in much greater numbers than in normal, dermatitic, and psoriatic skin. The percent epidermal area covered by CD1+ cells in psoriatic lesions (1.13%) and dermatitic lesions (1.65%) was significantly lower than that found in CTCL lesions (3.60%). CONCLUSION: --Epidermal immunohistologic patterns using anti-CD1, anti-CD2, anti-CD3, and anti-HLA-DR antibodies have the potential to distinguish CTCL from psoriasis and dermatitis in clinically ambiguous cases.
Adult↗
Ultrastructural analysis of the endothelial-pericyte relationship in diabetic cutaneous vessels.
The microvessels in the buttock skin of 15 patients with long-standing juvenile diabetes were studied both by electron microscopy and three-dimensional (3D) computer reconstruction of a prototypical diabetic postcapillary venule. Endothelial cell gaps were found in postcapillary venules and capillaries, but only in association with an increased deposition of basement membrane-like material in the vascular wall. In parallel with the increased amounts of deposited basement membrane-like material, the space between pericytes and endothelial cells was wider and the cytoplasmic processes that formed the contact points between them were longer and thinner than normal. Pericytes, devoid of any cytoplasmic contacts with the underlying endothelial cells, were observed as isolated cells within the outer third of the vascular wall in markedly thickened vessels. These observations offer an explanation for the known increased vascular permeability of diabetic vessels, and suggest a possible explanation for the development of diabetic retinopathy with aneurysm formation.
Adolescent↗
Correlation of laser Doppler wave patterns with underlying microvascular anatomy.
Laser Doppler velocimetry (LDV) was performed on the chest, back, and abdomen of four healthy volunteers. As the probe was moved over distances of 2-6 mm, the red-cell flux varied by 100%, but was associated with three distinctive wave patterns. Correlative skin biopsies showed that a high flux, pulsatile pattern superimposed on vasomotor activity was found when the probe was directly over an ascending elastic arteriole with its immediate branches; low flux, pulsatile flow with minimal or no vasomotor activity was found when the probe was off center relative to the ascending arteriole and its branches; and a low flux, non-pulsatile pattern occurred when the probe window was situated between ascending arterioles over an area in the upper horizontal plexus composed primarily of capillaries and post-capillary venules.
Humans↗
Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia.
We studied 10 cutaneous telangiectatic lesions of hereditary hemorrhagic telangiectasia (HHT), ranging in size from pinpoint to 2 mm, by light and electron microscopy. Four representative lesions were reconstructed by computer from serial 1- or 2-mm plastic embedded sections. The earliest clinically detectable lesion of HHT is a focal dilatation of postcapillary venules, which continue to enlarge and eventually connect with dilated arterioles through capillaries. As the vascular lesion increases in size, the capillary segments disappear and a direct arterio-venous communication is formed. This entire sequence of morphologic events is associated with a perivascular mononuclear cell infiltrate in which the majority of cells are lymphocytes and the minority are monocytes/macrophages by ultrastructure. Comparison of these findings with the telangiectatic mats of scleroderma and cherry angiomas revealed that the former, previously shown to be composed of dilated postcapillary venules, are also associated with perivascular infiltrates, but the latter, which are produced by capillary loop aneurysms, are not.
Adult↗
Ultrastructural and three-dimensional analysis of the contractile cells of the cutaneous microvasculature.
The three-dimensional relationships between smooth muscle cells and endothelial cells and between pericytes and endothelial cells in four segments of the microcirculation were analyzed by computer reconstructions from serial electron micrographs. In elastic-containing arterioles, the smooth muscle cells formed an inner longitudinal layer above and parallel to the elastica and an outer spiral layer. In the terminal arterioles the two layers of smooth muscle cells and elastica were replaced by a single smooth muscle cell that completely encircled the endothelial cell tube. The pericytes in the post-capillary venules completely encircled and gripped the endothelium through multiple contact points from their lateral processes. In the large venules the pericytes only partially encircled the endothelial cell tube and were more randomly placed.
Adult↗
Skin changes in menopause.
Skin signs and symptoms were examined in 46 menopausal women prior to estrogen replacement therapy. Several symptoms such as pruritus, bruising, dryness and thinning were seen more frequently in sun-exposed skin emphasizing the contribution of photoaging. At the end of a 6-mth treatment period, no significant difference was observed in the prevalence or severity of the cutaneous signs and symptoms when patients receiving transdermal 17 beta-estradiol (Estraderm) were compared with controls (the only exception was cutaneous flushing). Elastic fibers from sun-protected (buttock) skin of menopausal women were studied by light and electron microscopy. In 3 women (ages 30-37) with a history of premature menopause, the elastic fibers had several degenerative changes including coalescence of cystic spaces into lacunae, peripheral fragmentation, granular degeneration and splitting of the fibers into strands. Similar age-related ultrastructural changes are normally found in individuals that are at least 20 yrs older than these patients. These findings are suggestive of a relationship between premature aging of the dermal elastic fibers and estrogen deprivation.
Adult↗
Ultrastructure and organization of the cutaneous microvasculature in normal and pathologic states.
The cutaneous microvasculature is organized into upper and lower horizontal plexuses with the dermal capillary loops arising from the upper plexus. The arteriolar and venular sides of the microvasculature can be identified by the ultrastructure of the mural basement membrane material. Collecting venules present in the lower dermis contain valves. Periadventitial cells (veil cells) are present around all microvessels. Their size and number appear to correlate with the quantity of mural basement membrane material found in cutaneous vessels in diabetes, actinic damage, and chronological aging. The contractile cells of the vascular wall surround the endothelial cell tube in a manner suggesting specific functions. The smooth muscle cells in the arteriolar segment form a sleeve, whereas each pericyte in the postcapillary venular simultaneously makes many contacts with several underlying endothelial cells. The common telangiectases can be explained by abnormalities in this organization and ultrastructure rather than by neovascularization or random anastomoses. The macular telangiectases seen in scleroderma, generalized essential telangiectasia, and nevus flammeus are produced by dilatation of the postcapillary venules of the upper horizontal plexus. Cherry angiomas are produced by spherical and tubular dilatations of capillary loops in dermal papillae with tortuous cross-connections between individual loops. Angiokeratomas of Fabry and Fordyce have the ultrastructure of collecting venules that contain valves, and appear to represent the ectopic development or placement of small valve-containing collecting veins. The cutaneous lesions of hereditary hemorrhagic telangiectasia represent arteriovenous communications.
Animals↗
Angiogenic properties of normal and psoriatic skin associate with epidermis, not dermis.
Psoriasis is a chronic inflammatory and proliferative epidermal skin disease associated with prominent new vessels in the dermis. Heretofore, unresolved was the question which skin element causes stimulation of vessel formation in this lesion: the epidermis, the dermis, vessels themselves, inflammatory cells, and so forth. It has been argued that the dermis by means of its vessels is responsible for the rapid and prominent epidermal growth and that psoriasis is simply a dermal-induced epidermal disease. Recognizing that vascular proliferations do not occur in the absence of an angiogenic stimulus we asked where in psoriatic skin is that angiogenic element found. By using the rabbit cornea angiogenic assay, the vessel-stimulating properties of epidermis and dermis (separated after cold trypsinization overnight), collected from psoriatic-plaque skin and normal skin both nonpsoriatic and psoriatic patients, were measured. The corneas were examined on days 2, 4, 8, 10, and 12 and graded from 1 to 5+ for vessel growth. Psoriatic plaque epidermis revealed a 4 to 5+ stimulus (8 of 12 corneas). Epidermis from normal subjects or from nonlesional psoriatic patient skin also revealed a 4 to 5+ stimulus (3 of 5 and 5 of 8, respectively). In no case was the dermal implant from normal (7 implants) or psoriatic patients (3 implants of lesional skin) angiogenic. The angiogenic activity of epidermis is stable to freezing and boiling. This study indicates that the vessel-stimulating properties of psoriatic and nonpsoriatic skin are associated with the epidermis and that the developing psoriatic lesion may involve complex epidermal to dermal as well as dermal to epidermal signals.
Adult↗
Elastic fiber and microvascular abnormalities in aging skin.
In summary, the aging process in skin has at least two major manifestations: elastic fiber abnormalities involving degradation and assembly, and microvascular wall alterations of widening and atrophy depending on the functional state of the veil cell. The abnormalities of the elastic fiber network most likely correlate with the increasing cutaneous laxity associated with aging. The microvascular abnormalities are not easily related to any specific clinical feature of aging skin. The finding of identical abnormalities in the skin of juvenile diabetes strengthens this hypothesis, as well as suggesting that these alterations are accelerated in diabetic patients. Diabetic skin might be another model system for studying cutaneous aging.
Aged↗
A hypothetical explanation for the aging of skin. Chronologic alteration of the three-dimensional arrangement of collagen and elastic fibers in connective tissue.
To provide a morphologic basis for a better understanding of the "aging" of human skin, the authors studied the three-dimensional arrangement and chronological alterations of the fibrous components of the connective tissue using rats aged 2 weeks to 24 months with a new technique for scanning electron microscopy. These studies showed that with postnatal growth there was a dynamic rearrangement of the collagen and elastic fibers: an ordered arrangement of mature collagen bundles was attained by producing a distortion of the elastic fiber meshwork of relatively straight fibers. During adulthood, there was a subsequent tortuosity of the distorted elastic fibers coupled with an incomplete rebuilding of the elastic fiber network, laid down in a form to interlock with the collagen bundles. These changes provide a model for explaining manifestations of aged skin, such as laxity, sagging, and wrinkling. The tortuously fixed elastic fibers imply that they have been stretched and have lost their original elasticity and ability to restitute short and straight. Interlocking of both collagen and elastic fibers should disturb the two independent fibrous systems, as would normally be the case, and thus decrease tissue compliance.
Aging↗
Scanning electron microscope study of elastic fibers of the loose connective tissue (superficial fascia) in the rat.
A combination of intravascular resin injection and formic acid incubation was utilized to study the three-dimensional arrangement of the elastic fibers in the loose connective tissue (superficial fascia) of the rat limb by scanning electron microscopy (SEM). The cast of the microvasculature served as a scaffolding for the otherwise collapsible connective tissue. SEM study demonstrated that the elastic fibers did not form an anastomosing network but were arranged in multiple layers. The fibers in each layer lay parallel to each other but were oriented differently from the fibers in the layers on either side, thereby producing a meshwork. Each individual fiber was composed of a small bundle of discrete fibrils. Some of these component fibrils separated from the parent fiber and united with other fibers, thus producing branching. The elastic fiber either decreased or grew in size by the respective sharing or joining of these component fibrils with neighboring fibers in their respective layers. Interconnections between elastic fibers of different layers were rare. These findings may provide a morphological explanation for the characteristic function of the superficial fascia, which allows the skin and underlying muscles to have a rapid and extensive alteration in their relative positions.
Animals↗
Progression of pigmented purpura-like eruptions to mycosis fungoides: report of three cases.
The cases of three relatively young male patients with pigmented purpura-like eruptions evolving to mycosis fungoides are described. Initially, the eruptions, both clinically and histologically, very closely resembled pigmented purpuric dermatitis. After a follow-up period averaging 8.4 years, diagnostic histologic changes of mycosis fungoides were observed. Although uncommon, mycosis fungoides should be considered in the differential diagnosis of pigmented purpuric eruptions.
Adolescent↗
Immunology and the skin. Current concepts.
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Animals↗