Scanning electron microscopic study of the capillary loops in the dermal papillae. Skin of the hand of the Japanese monkey (Macaca fuscata)

The microvasculature of the skin of the hand of Japanese monkeys was examined by means of scanning electron microscopy of corrosion casts. The vasculature of all areas of the skin of the hand was examined and divided into three structures excluding the nail bed: (1) In the ball of the finger, the typical structure of the capillary loops was studied. Capillary loops were formed out of not just one capillary vessel, but two or three vessels. Each capillary vessel arose and divided into several branches at the papilla, and they became descending limbs. After the loop passed a hairpin turn, the descending limbs were 1.5 times larger than the ascending limbs in the intrapapillary portion, and they became extrapapillary venules. The descending limbs connected with the postcapillary venules in the postpapillary portion and with the horizontal network. The postcapillary venules fused with each other (1-5 loops) to form the primary and secondary venous arcades. (2) In the thenar eminence, the capillary loops were a little lower, and their grooves were wider than in the ball of the finger. The characteristic structure in this area was the interpapillar capillary network. (3) In the lateral side of the finger, the number of capillary loops formed by the arterial capillary network of the subepidermal layer was smaller. The capillary loops here had the lowest height and a simple structure.     

Alterations of islet microvasculature in mice treated with low-dose streptozocin.

Islet capillary area was followed daily in mice after treatment with low-dose streptozocin (LDS), in order to elucidate the exact period during which the insular vascular bed undergoes a significant reduction. Forty C57BL6/J mice were diabetized with 5 x 40 mg streptozocin (STZ)/kg body wt and killed 6, 8, 9, 10, 11, 12, 15 or 18 days after the first STZ injection. Pancreases were sectioned and processed by staining for alkaline phosphatases using a method devised by Gomori. The percentage of the islet parenchymal area occupied by intra-islet capillaries was measured using a Videoplan videoanalyzer. LDS treatment did not significantly alter the islet capillary area up to day 8; the first signs of reduction were seen on days 9 and 10 (islet capillary area at days 9 and 10 respectively was 2.68% and 2.60% of controls). At day 11 a dramatic decrease in islet capillary area was seen (1.38%), which was not accompanied by a similar reduction of the islet parenchymal area. The reduction in islet capillary area continued to progress up to day 15 by which time it had achieved the lowest level (0.72%). On day 18, values remained practically unchanged.     

Alterations of islet microvasculature in mice treated with low-dose streptozocin

Summary Islet capillary area was followed daily in mice after treatment with low-dose streptozocin (LDS), in order to elucidate the exact period during which the insular vascular bed undergoes a significant reduction. Forty C57BL6/J mice were diabetized with 5×40 mg streptozocin (STZ)/kg body wt and killed 6, 8, 9, 10, 11, 12, 15 or 18 days after the first STZ injection. Pancreases were sectioned and processed by staining for alkaline phosphatases using a method devised by Gomori. The percentage of the islet parenchymal area occupied by intra-islet capillaries was measured using a Videoplan videoanalyzer. LDS treatment did not significantly alter the islet capillary area up to day 8; the first signs of reduction were seen on days 9 and 10 (islet capillary area at days 9 and 10 respectively was 2.68% and 2.60% of controls). At day 11 a dramatic decrease in islet capillary area was seen (1.38%), which was not accompanied by a similar reduction of the islet parenchymal area. The reduction in islet capillary area continued to progress up to day 15 by which time it had achieved the lowest level (0.72%). On day 18, values remained practically unchanged.     

Integrated study of the structural and metabolic degeneration of skin during 4 degrees C storage in nutrient medium

Integrated studies of the structural and metabolic degradation of skin during 4 degrees C refrigerated storage in Eagle's minimal essential medium were undertaken. Skin degeneration occurred in three phases during the first 7 weeks of refrigeration. Phase I (Days 1-10) was characterized by the release of cellular debris and leakage of intracellular enzymes into the storage medium, shrinkage of the epithelium, and vacuolization and cell loss in the vascular bundles of the papillary dermis. The release of debris was accelerated by a 2-hr incubation of the skin at 25 and 37 degrees C prior to 4 degrees C storage. The ability of dermal cells to metabolize glucose, aspartic acid, glutamic acid, ornithine, and orotic acid to carbon dioxide dropped to low levels during Phase I. Phase II (Days 11-30) was characterized by a period of less intense physical decay, but with continued cellular and vascular degeneration. By the third week, there was nearly total loss of recognizable vascular bundles in the papillary dermis. Phase III (Days 31-58) was characterized by the exfoliation of large amounts of cellular debris and significant loss of structural integrity. By the fifth week, nearly all of the nuclei in the epidermis became pyknotic, and the vascular bundles of the reticular dermis were lost. Previous reports of the maximum allowable duration of skin storage at 0-8 degrees C have ranged from 0.3 to 185 days; however, our findings suggest that the useful limit of refrigerated skin storage in nutrient medium is 1 week if physiological function and structural integrity are desired for optimum postgraft performance.     

Regional differences in capillary density of the normal human dermis

Quantitative study of the capillary density of normal dermis of 113 biopsy specimens taken from 20 body sites from 6 cadavers was carried out. Histologic quantification of dermal capillaries using the alkaline phosphatase method to delineate vascular endothelium and automated image analysis demonstrates statistically significantly greater capillary density in the head-face/neck region both in the papillary and reticular dermis than in the lower parts of the body. The smallest numbers of the dermal capillary density were noted in the calf and shin areas. These data support the hypothesis that random-pattern skin flaps can be safely raised longer in the face and neck than in other parts of the body.     

Striae albae: a morphological study on the human skin

Specimens of abdomen skin, comprising alternate areas of striae albae and healthy skin, were removed during surgical lipectomy from multiparous and obese women between the ages of 24 and 53 years. A flattening and thinning of the striae albae surface and the almost complete disappearance of dermal papillae was observed in paraffin and thin sections. The papillary dermis was found to be almost completely replaced by straight bundles of collagen fibres running parallel to the skin surface. Immunofluorescence data revealed in these bundles high positivity for type I collagen. The underlying reticular dermis was also found to contain large densely packed bundles of collagen fibres running parallel to the skin surface. Both papillary and reticular dermis collagen fibres were mainly arranged orthogonally to the main axis of the stria. Furthermore, the density of the collagen fibre bundles and the diameter of the collagen fibrils was found to be greater than that of the clinically healthy skin. A larger number of elastic fibres, which presented an abnormal ultrastructural appearance, were visible in pathological papillary and reticular dermis.     

Changes in the parameters of skin capillaries during the adaptation of students from the countries of Asia, Africa and Latin America

Time-dependent changes in diameters of various parts of the capillaries, distances between loops of the skin papillary capillaries in the nail wall and number of functioning capillaries per 1 mm2 of the skin surface have been studied biomicroscopically in foreign students, arrived from hot countries, during the process of their adaptation. Reorganization of these skin capillary parameters, actively participating in processes of heat exchange, demonstrate a time-dependent character. Therefore, by means of regressive analysis it is possible to approximate dynamics of the initial data using suitable theoretical models. The dynamics of average meanings of the capillary diameters in the arterial part subordinates to the hyperbolic dependence, changes of other parameters approach the rectilinear regression.     

Collagen types I, III, and V in human embryonic and fetal skin

The dermis of human skin develops embryonically from lateral plate mesoderm and is established in an adult-like pattern by the end of the first trimester of gestation. In this study the structure, biochemistry, and immunocytochemistry of collagenous matrix in embryonic and fetal dermis during the period of 5 to 26 weeks of gestation was investigated. The dermis at five weeks contains fine, individual collagen fibrils draped over the surfaces of mesenchymal cells. With increasing age, collagen matrix increases in abundance in the extracellular space. The size of fibril diameters increases, and greater numbers of fibrils associate into fiber bundles. By 15 weeks, papillary and reticular regions are recognized. Larger-diameter fibrils, larger fibers, denser accumulations of collagen, and fewer cells distinguish the deeper reticular region from the finer, more cellular papillary region located beneath the epidermis. The distribution of collagen types I, III, and V were studied at the light microscope level by immunoperoxidase staining and at the ultrastructural level by transmission (TEM) and scanning electron microscopy (SEM) with immunogold labeling. By immunoperoxidase, types I and III were found to be evenly distributed, regardless of fetal age, throughout the dermal and subdermal connective tissue with an intensification of staining at the dermal-epidermal junction (DEJ). Staining for types III and V collagen was concentrated around blood vessels. Type V collagen was also localized in basal and periderm cells of the epidermis. By immuno-SEM, types I and III were found associated with collagen fibrils, and type V was localized to dermal cell surfaces and to a more limited extent with fibrils. The results of biochemical analyses for relative amounts of types I, III, and V collagen in fetal skin extracts were consistent with immunoperoxidase data. Type I collagen was 70-75%, type III collagen was 18-21%, and type V was 6-8% of the total of these collagens at all gestational ages tested, compared to 85-90% type I, 8-11% type III, and 2-4% type V in adult skin. The enrichment of both types III and V collagen in fetal skin may reflect in part the proportion of vessel- and nerve-associated collagen versus dermal fibrillar collagen. The accumulation of dermal fibrillar collagen with increasing age would enhance the estimated proportion of type I collagen, even though the ratios of type III to I in dermal collagen fibrils may be similar at all ages.     

Tumor markers and oncogene expression in thyroid cancer using biochemical and immunohistochemical studies.

In 111 thyroid cancer patients consisting of 89 papillary carcinomas, 17 follicular carcinomas, 2 medullary carcinomas, 1 squamous cell carcinoma and 2 malignant lymphomas, the levels of 12 tumor markers, including thyroglobulin (Tg), were measured in the serum by radioimmunoassay and radioimmunoassay related methods. Serum levels of Tg were elevated in 58.6%, those of CA-M26 in 15.7%, CA 19-9 in 5.3%, CT in 3.6%, NSE in 3.6%, CA 15-3 in 2.6%, CA 125 in 2.6%, CEA in 0.9%, CA-M 29 in 0%, ferritin in 0%, SCC in 0% and AFP in 0% of cases. Among the patients, there was a case of thyroid carcinoma secreting thyroglobulin and CA 19-9, both of whose titer decreased after surgery. Immunohistochemical studies were carried out on 57 of the above mentioned patients plus 6 anaplastic carcinomas, 15 adenomas, 5 adenomatous goiters, 6 Hashimoto's thyroiditis, 15 Graves' disease and 15 normal subjects. CA 19-9 was positive in 58% of the papillary carcinomas, EGF in 73% of papillary carcinomas, 67% of anaplastic carcinomas, and 33% of follicular carcinomas, while EGF-R was found in 73% of the papillary carcinomas, and 33% of the follicular carcinomas. Enhanced expression of ras p 21 oncogene and (c-myc oncogene) was demonstrated in 100% (100%) of anaplastic carcinomas, in 100% (67%) of follicular carcinomas and in 63% (90%) of papillary carcinomas. Our results indicate that a better tumor marker is required and more extensive molecular oncology research should be pursued.     

Normative intercapillary distance and vessel density data in the temporal retina assessed by wide-field spectral-domain optical coherence tomography angiography

A limitation of conventional optical coherence tomography angiography (OCTA) is the limited field of view normally used in data acquisition. As the technology improves, larger fields of view that capture information away from the macular are being explored in order to provide an enhanced ability to detect pathology. However, normative measurements for important OCTA metrics like vessel density and intercapillary distance are not currently well-characterized in the peripheral retina. In this prospective study, we measured vessel density and intercapillary distance of the superficial vascular complex, ganglion cell layer plexus, and deep capillary plexus in montaged macular/temporal scans from 53 (33 men) healthy volunteers. Vessel density and intercapillary distance were also compared across different regions of the retina, including along arcs at separate distance from the fovea. Compared to the central macular region, the temporal retina had significantly lower vessel density, decreased thickness, and greater intercapillary distance in the superficial vascular complex, GCLP ganglion cell layer plexus, and deep capillary plexus (Wilcoxon rank sum test P < 0.001), with each of the plexuses examined here showing a general decrease in vessel density and an increase in intercapillary distance towards the temporal region. No significant difference was noted comparing corresponding vessel density and intercapillary distance regions above and below the macula, and multiple linear regression showed that age and intraocular pressure were not associated with vessel density and intercapillary distance in most models. Repeatability analysis reported as intraclass correlation coefficients demonstrated moderate to excellent reliability of vessel density and intercapillary distance in all OCTA layers. These results should help provide an enhanced baseline to help identify vascular pathology in the peripheral retina.     

Changes in location of type I collagen synthesis in two stages of fetal calf skin as revealed by in situ hybridization

The distribution of sites of type I collagen gene expression was studied in frozen sections of skin of 4 and 9 month-old calf fetuses by in situ hybridization using a human pro-alpha 1 type I collagen cDNA. The labelling varied with the different layers of the dermis and with the developmental stage considered. In the 4 month old fetus skin, the label appeared concentrated in the upper layer of the dermis at the lewel of the hair follicles. In the 9 month-old fetus skin, the difference of labelling between upper papillary dermis and lower dermis was less marked. Comparatively the distribution of the extracellular type I collagen was determined by indirect immunofluorescence. This collagen appeared present throughout the whole dermis with slight variations at 4 months, where there was less extracellular collagen near the hair bulbs. These results are in agreement with the idea that the collagen synthesis follows cutaneous differentiation. In addition, they support the hypothesis that collagen is deposited once morphogenetic events have occurred and plays thus a stabilizing role in formation of cutaneous appendages.     

Comparative characteristics of the capillary bed of the temporal lobe and the mammillary bodies of the hypothalamus in man in relation to age

The data have been obtained on regional differences in structure of the capillary bed in the temporal cortex of the cerebrum (TCC) and in the papillary bodies of the human thalamus (PBHT) during various age periods. The capillary diameter and nuclear volume is greater in perivascular gliocytes of the TCC than in those of the PBHT. With ageing the capillary diameter and hypertrophy of the endotheliocytic nuclei is noted to increase in both areas of the brain.     

Tenascin/hexabrachion in human skin: biochemical identification and localization by light and electron microscopy

Tenascin/hexabrachion is a large glycoprotein of the extracellular matrix. Previous reports have demonstrated that tenascin is associated with epithelial-mesenchymal interfaces during embryogenesis and is prominent in the matrix of many tumors. However, the distribution of tenascin is more restricted in adult tissues. We have found tenascin to be present in normal human skin in a distribution distinct from other matrix proteins. Immunohistochemical studies showed staining of the papillary dermis immediately beneath the basal lamina. Examination of skin that had been split within the lamina lucida of the basement membrane suggested a localization of tenascin beneath the lamina lucida. In addition, there was finely localized staining within the walls of blood vessels and in the smooth muscle bundles of the arrectori pilorem. Very prominent staining was seen around the cuboidal cells that formed the basal layer of sweat gland ducts. The sweat glands themselves did not stain. The distribution of tenascin in the papillary dermis was studied at high resolution by immunoelectron microscopy. Staining was concentrated in small amorphous patches scattered amongst the collagen fibers beneath the basal lamina. These patches were not associated with cell structures, collagen, or elastic fibers. Tenascin could be partially extracted from the papillary dermis by urea, guanidine hydrochloride, or high pH solution. The extracted protein showed a 320-kD subunit similar to that purified from fibroblast or glioma cell cultures. We have developed a sensitive ELISA assay that can quantitate tenascin at concentrations as low as 5 ng/ml. Tests on extracts of the papillary dermis showed tenascin constituted about 0.02-0.05% of the protein extracted.     

The skin of primates. XLI. The skin of the silver marmoset—Callithrix (= Mico) Argentata

The skin of the silver marmoset, Callithrix (= Mico) argentata Linnaeus, has many outstanding characteristics. The unusually thin epidermis and dermis are generally devoid of melanotic melanocytes. The surface of the interramal gular region is peppered with small, elevated papillae; that of the corpus penis is characterized by keratinized, proximally directed hollow spines in whose cavities are organized nerve end-organs and capillary loops. Cholinesterase-reactive papillary nerve end-organs and Meissner corpuscles populate all volar friction surfaces. A highly vascular dermis and subcutaneous fat pad partially contribute to the characteristic rubicund color of the face, external ears, and anogenital region. Many body surface hairs are accompanied by the classic Haarscheibe of Pinkus. Sinus hairs are plentiful; a circumscribed vibrissa-bearing eminence is located on the ventral ulnar aspect of each wrist. Alkaline phosphatase-positive, stellate-shaped cells are found on the outer root sheath and epithelial sac of active and quiescent hairs in all cephalic regions; such cells are not argyrophilic, aurophilic, or osmiophilic. Hairs grow in linear perfect sets of 3 to 5 follicles; they do not grow singly on the cheek. Large sebaceous glands contain alkaline phosphatase in their peripheral acini; extensive fields of gigantic multilobular sebaceous glands contribute to the distinct, opaque-white color of the scrotal skin. Numbers of apocrine sweat glands are diminished in cephalic regions but one gland occurs with each hair follicle in the axilla, scrotum, suprapubic region, and ulnar eminence. Relatively avascular eccrine sweat glands are confined to the volar friction surfaces. Their secretory coils contain sporadically distributed glycogen and phosphorylase and surrounding nerves are much more reactive for acetyl- than butyrylcholinesterase.     

Eosinophil degranulation. An immunologic determinant in the pathogenesis of the Mazzotti reaction in human onchocerciasis

Onchocerciasis patients treated with diethylcarbamazine often undergo a severe inflammatory response, the Mazzotti reaction. To assess the eosinophil's role in the pathogenesis of the Mazzotti reaction, we obtained serial blood, plasma, and skin biopsy specimens from 21 heavily infected patients and 3 endemic controls, both before and during therapy with diethylcarbamazine. Samples were analyzed for blood eosinophils, plasma levels of eosinophil granule major basic protein (MBP) and eosinophil-derived neurotoxin, eosinophil infiltration and eosinophil and mast cell degranulation in the skin. After the first dose of diethylcarbamazine, blood eosinophils fell from a pre-treatment level of 888 +/- 111 to 203 +/- 42 cells/mm3 at 8 h. This decrease was followed by a marked eosinophilia developing over the remaining 7 days of treatment and 14 days of follow-up. Plasma eosinophil-derived neurotoxin levels increased from 56 +/- 4 ng/ml pretreatment to a peak of 82 +/- 9 ng/ml at 8 h and returned to pretreatment levels by 48 h. Beginning at 12 h, plasma MBP levels increased from 730 +/- 74 ng/ml pretreatment to a peak of 1140 +/- 74 ng/ml after 5 days. Pretreatment skin biopsies stained for MBP by immunofluorescence showed a bright fibrillar pattern in the dermis consistent with chronic eosinophil degranulation; the MBP was localized on elastic tissue fibers. After treatment, skin biopsy specimens showed both the pretreatment fibrillar MBP staining pattern as well as focal eosinophil degranulation. Deposition of MBP around microfilariae in the papillary dermis was visible as early as 1.5 h. The lowest blood eosinophil levels and peak plasma eosinophil-derived neurotoxin levels coincided with the infiltration and degranulation of eosinophils in the skin. Mast cell degranulation in the skin was maximal by the first posttreatment biopsy (1.5 h) coincident with the beginning of eosinophil degranulation. Although the pathogenesis of the Mazzotti reaction is clearly complex, our results indicate that eosinophil degranulation is characteristic of the response and that it occurs with a time course suggestive of a role for the eosinophil in determining the clinical and pathologic manifestations of the reaction.     

Morphofunctional characteristics of microcirculation in the skin of girls 5-17 years of age

In 261 girls year-to-year morphofunctional transformations of spatial composition of the skin microcirculatory bed have been studied at rest and after a dynamic local load. By means of biomicroscopy main regularities in development of the skin capillary network have been revealed in the nail torus in the postnatal ontogenesis. Formation of the microvessels reactivity during various age periods and maturation of mechanisms of the compensatory-adaptive reactions are connected with formation of the definitive composition of the microcirculatory bed, that in girls corresponds to 11-12 years. Qualitative transformations in the skin capillary network bring certain quantitative changes in the structural microcirculatory parameters--increasing diameter of microvessels and increasing density of functioning capillaries.     

Structural changes and hemodynamic relations in the microcirculatory bed of the mesentery of the white rat during the period of sexual maturation

Structural changes and hemodynamic relations have been studied in the microcirculatory bed of the white rat small intestine mesentery during sex maturation (from the 3d up to the 10th week of the postnatal development). All calculations are performed regarding the mesenteric segment limited with two intestinal arteries, which is considered as an elementary microvascular module. Complication of the microcirculatory bed construction takes place at the expense of increasing number (nearly five-fold) of microvessels in the segment and increase of the capillary network density. The hemodynamic factor plays a certain role for stimulating the process of the capillary growth. The definitive structure of the mesenteric microcirculatory bed is completed by the 7th week. The main rearrangement of the microcirculatory system during the developmental process from a simple arterio-venular loop up to a complex microcirculatory bed with a branching capillary network is performed within the limits of the mesenteric segment.     

Main principles of the organization of the microcirculatory bed of the human greater omentum in early ontogenesis

The formation process of the terminal blood bed of the greater omentum has been studied in 42 human fetuses 14--28-week-old. The main peculiarities of the greater omentum blood bed by the 14th week of development are: paired arrangement of the afferent and deferent blood vessels and loop-shaped type of capillary growth, that joining the arteriole and venule, lend the blood stream a maximally centralized character. In 15--16 weeks of the fetal development in the omentum another type of the vascular growth occurs, characterized with appearance of single angioblastic processes that branch off the apex of the capillary loops. As a result new capillaries form; they connect apices of the capillary loops, that in their turn make bases for developing a true capillary network. Together with this, presence in ontogenesis of an autochthonous way of capillary appearance is proved, their connection with the closed blood stream is followed. Distinguishing of the loop-shaped stage in the capillary growth determines certain difference between vasculogenesis in ontogenesis and the vascular growth at reparative regeneration, since the base for the latter is only the capillary growth by means of single angioblastic processes.     

Nerves and nerve endings in the skin of tropical cattle.

The nerves and nerve endings in the skin of tropical cattle were studied using histological and histochemical techniques. Many nerve trunks and fibres were present in the reticular and papillary dermis in both hairy and non-hairy skin sites. In non-hairy skin locations such as the muzzle and lower lip, encapsulated endings akin to Krause and Ruffini end bulbs, which arise from myelinated nerve trunks situated lower down the dermis were observed at the upper papillary layer level. Some fibre trunks seen at this level extended upwards to terminate within dermal papillae as bulb-shaped longitudinally lamellated Pacinian-type endings, while other onion-shaped lamellated nerve structures were located either within dermal papillae or near the dermo-epidermal area. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. Intraepidermal free-ending nerve fibres, appearing non-myelinated were observed in areas with thick epidermis. On hairy skin sites, however, organized nerve endings or intraepidermal nerve endings were not readily identifiable.     

A biphasic multilayer computational model of human skin

The present study investigates the layer-specific mechanical behavior of human skin. Motivated by skin’s histology, a biphasic model is proposed which differentiates between epidermis, papillary and reticular dermis, and hypodermis. Inverse analysis of ex vivo tensile and in vivo suction experiments yields mechanical parameters for each layer and predicts a stiff reticular dermis and successively softer papillary dermis, epidermis and hypodermis. Layer-specific analysis of simulations underlines the dominating role of the reticular dermis in tensile loading. Furthermore, it shows that the observed out-of-plane deflection in ex vivo tensile tests is a direct consequence of the layered structure of skin. In in vivo suction experiments, the softer upper layers strongly influence the mechanical response, whose dissipative part is determined by interstitial fluid redistribution within the tissue. Magnetic resonance imaging-based visualization of skin deformation in suction experiments confirms the deformation pattern predicted by the multilayer model, showing a consistent decrease in dermal thickness for large probe opening diameters.