Aquagenic pruritus.

Three patients were studied in whom brief contact of the skin with water at any temperature evoked intense itching without visible changes in the skin. The patients were otherwise apparently healthy, and this chronic and disabling disorder tended to attract a "psychogenic" label. Pharmacological studies showed that the condition was associated with local release of acetyl choline in the skin, mast-cell degranulation, and raised blood histamine concentrations. It responded well to antihistamines in two of the three patients. Aquagenic pruritus is probably common, but it is generally unrecognised and may be misdiagnosed. Antihistamines may induce a good therapeutic response.     

Mechanism of skin morphogenesis. I. Analyses with antibodies to adhesion molecules tenascin, N-CAM, and integrin.

To understand cell interactions during induction of skin appendages, we studied the roles of adhesion molecules N-CAM, tenascin, integrin, and fibronectin during feather development. Tenascin appeared in a periodic pattern on epithelia and was so far the earliest molecule detected in placodes. Three placode domains were identified: the anterior was positive for tenascin, the distal positive for N-CAM, and the posterior lacking both. Integrin appeared in dermal-epidermal junctions of placodes. In feather buds, sagittal sections revealed a transient anterior-posterior asymmetry with tenascin and N-CAM enriched in the anterior mesoderm. Tangential sections revealed a lateral-medial asymmetry with tenascin distributed in a ring shape and N-CAM in an "X" shape. Integrin was diffusely distributed within buds. Later tenascin and N-CAM were enriched in dermal papilla, the inducer of skin appendages. Perturbation of embryonic skin explant cultures with antibodies showed that anti-integrin beta 1 and anti-fibronectin blocked epithelial-mesenchymal interaction, anti-N-CAM caused uneven segregation of mesenchymal condensation, and anti-tenascin inhibited feather bud elongation. Dose-response curves showed gradual effects by these antibodies. The results indicated that these adhesion molecules are independently regulated and each contributes in different phases during morphogenesis of skin appendages.     

Chronic graft-versus-host disease (GVHD) as a model for scleroderma. I. Description of model systems

A model murine system of chronic graft-versus-host disease (GVHD) was explored to determine its suitability for studying scleroderma-like syndromes. The basic protocol was to inject lymphoid cell suspensions into irradiated semiallogeneic or allogeneic recipients which had been irradiated. Serial body weights, skin biopsies, and anti-nuclear antibodies were followed. Changes seen in the skin included increased collagen deposition, a mononuclear infiltrate deep in the dermis, loss of dermal fat, and "dropout" of skin appendages such as hair follicles. Body weight loss was a sensitive index of GVHD. Anti-nuclear antibodies occurred at times, but did not correlate with the tissue changes in the skin of mice undergoing GVHD. This chronic GVHD syndrome was produced across major and minor histocompatibility barriers. The most consistent findings were seen in BALB/c recipients of B10.D2 cells. These strains are nonreactive in unprimed mixed-leukocyte cultures. This combination represents primarily a GVH reaction against minor antigens where the HVG reaction is suppressed by irradiation. Some data suggest that the cutaneous changes may be reversible with time.     

The non-neuronal cholinergic system of human skin.

In human skin both resident and transiently residing cells are part of the extra- or non-neuronal cholinergic system, creating a highly complex and interconnected cosmos in which acetylcholine (ACh) and choline are the natural ligands of nicotinic and muscarinic receptors with regulatory function in both physiology and pathophysiology. ACh is produced in keratinocytes, endothelial cells and most notably in immune competent cells invading the skin at sites of inflammation. The cholinergic system is involved in basic functions of the skin through autocrine, paracrine, and endocrine mechanisms, like keratinocyte proliferation, differentiation, adhesion and migration, epidermal barrier formation, pigment-, sweat- and sebum production, blood circulation, angiogenesis, and a variety of immune reactions. The pathophysiological consequences of this complex cholinergic "concert" are only beginning to be understood. The present review aims at providing insight into basic mechanisms of this highly complex system.     

Skin penetration of infective hookworm larvae. II. The path of migration of infective larvae of Ancylostoma braziliense in the metacarpal foot pads of dogs

The hairless metacarpal foot pads of six hookworm-free puppies were exposed to infective larvae of Ancylostoma braziliense. Serial sections of the biopts stained with Harris' haematoxylin and eosin showed that the infective larvae are able to penetrate the toughest region of canine skin. Pores of eccrine sweat glands did not seem to constitute sites of entry and no larvae were detected in these glands. Larvae were only observed in the epidermis. The histopathology of the infected skin of the foot pads of the puppies was similar to that in human skin with "creeping eruption" as described by Fülleborn (1927). The biopts appeared to consist of hairy skin as well. In the unexposed adjacent hairy skin of the foot pads, larvae were also observed. They were found in the epidermis, hair follicle systems and dermis, suggesting that the migration from the epidermis into deeper tissue depends on the presence of the hair follicle systems.     

Body weight: its relation to tissue composition, segment distribution, and motor function. I. Interspecific comparisons.

The composition of skin, muscle, and bone and their distribution throughout the body are compared for "advanced" or "specialized" species (Alouatta, Macaca, Canis, Felis, Lepus); smaller, more closely related species (Tupaia and the Lorisidae); and several species within the same ecosystem (Barro Colorado Island, Panama). Among the most significant variables, the skin of sloths, howlers and macaques constitutes more than 12% of body weight, whereas greyhound skin is 5% of weight; sloth and howler muscle are 25% of weight, macaque muscle about 40% of weight, greyhound and agouti muscle over 50% of weight. In tree shrews and galagos muscle is heavier (35%) than in pottos and slow lorises (below 28%), but bone and skin are lighter. All species differ in the segmental distribution of weight. Cats have light tails, light feet and heavy thighs, whereas howlers have heavy tails, heavy feet, and light thighs. The galagos have heavy hindlimbs and tails, the pottos and lorises have reduced tails and approximately equal fore- and hindlimbs. Convergences in segment pattern (sloths with pottos and lorises, marmosets with tree shrews, owl monkeys with galagos, cebus with macaques) as well as divergences are documented. All weight-of tissue and weight-of-segment variables are correlated directly with locomotor adaptation.     

One-stage reconstruction for defects of the mouth using a sternomastoid myocutaneous flap.

The sternomastoid muscle has 3 blood supplies: the occipital artery superiorly, the superior thyroid artery in the middle, and the thyrocervical trunk below. We report the use of a myocutaneous flap consisting of a "paddle" of skin on the end of a pedicle of sternomastoid muscle--with the latter based either on its superior or inferior blood supply. Fourteen such flaps have been used successfully in 13 consecutive patients for one-stage reconstructions of defects of the oral cavity and oropharynx. Although there was partial epithelial loss of the skin "paddle" in 7 cases, in each case the surviving dermis became resurfaced with epithelium.     

A method for repair of cryptotia.

The key points in our method of repair of cryptotia are (1) to cover the skin defect on the posterior aspect of the ear after it is dissected from the head, and (2) to repair the cartilaginous deformity. We describe the use of a temporal skin flap for the former. For the latter, we make parallel incisions on the back of the superior crus and transfer a small graft of conchal cartilage there. The conchal cartilage graft "splints" the repaired crus against cicatricial contracture.     

Genetic control of plastid carotenoids and transformation in the skin of Cucurbita pepo L. fruit

Summary The influence of allelic state of gene B on skin pigmentation in two cultivars of Cucurbita pepo L. has been studied. Total carotenoids were lower at early stages of fruit development in cultivar (cv.) Early Prolific (EP) BB YY fruit skin, than in EP B ⁺ B ⁺ YY fruit skin, but no differences were observed in total skin carotenoids twenty days after anthesis. Total carotenoids were lower in cv. Fordhook Zucchini (FZ) BB yy fruit skin, than in FZ B ⁺ B ⁺ yy fruit skin at all developmental stages from anthesis to maturity. Both green and yellow tissues contained typical foliar carotenoids. The carotenoids from yellow fruit skin of both EP genotypes and of FZ BB were characterized by a low carotene: xanthophyll ratio, with a high proportion of the xanthophylls esterified to fatty acids. The xanthophylls of the yellow tissues were esterified with 120, 140, 160 fatty acids. The carotenoids from the green fruit skin of FZ B ⁺ B ⁺ had a higher percentage of carotenes (primarily -carotene) and a lower percentage of esterified xanthophylls. Spectral shapes of carotenoid fractions from all yellow tissues were similar and distinguishable from those of green FZ B ⁺ B ⁺ tissue. The results of these studies are discussed in terms of the genetic control of plastid transformation in Cucurbita pepo L.New Jersey Agricultural Experiment Station No. D99201 (NE-9) 32-83, supported by state funds and funds from the Rutgers University Research Council     

Antibodies to guinea pig lymphokines. II. Suppression of delayed hypersensitivity reactions by a "second generation" goat antibody against guinea pig lymphokines.

A "second generation" antibody to a highly purified lymphocyte product was raised in a goat against material eluted from a rabbit anti-guinea pig lymphokine immunoadsorbent column. This anti-lymphokine serum, in constrast to anti-lymphocyte serum (ALS) did not appear to contain cytotoxic antibodies directed against membrane antigens on guinea pig lymph node lymphocytes. Furthermore, the anti-lymphokine serum did not inhibit the formation of spontaneous T rosettes nor significantly depress lymphocyte response to mitogens. The anti-lymphokine serum totally suppressed the delayed skin reactivity to PPD and contact sensitivity to DNCB when injected intradermally around the site of antigen challenge. By contrast, intradermally injected ALS did not appear to suppress the PPD response in sensitized guinea pigs. Intravenously and i.p. administered anti-lymphokine serum was somewhat less effective in suppressing the delayed skin response to PPD. The intradermal injection of the antiserum had no effect on nonspecific inflammation evoked by turpentine-olive oil or on the extravasation of circulating Evans blue evoked by intradermally injected histamine. Histologic examination of 24-hr DNCB-induced skin lesions from sensitized guinea pigs treated with intradermally injected anti-lymphokine serum showed marked reduction of mononuclear infiltration of the dermis and of epidermal lesions, as compared with skin sites taken from sensitized animals pretreated with normal goat serum. The anti-lymphokine serum injected i.v. also markedly reduced the perivascular infiltration of the dermis and subcutis in skin reaction sites from sensitized animals challenged with PPD. Intravenous treatment with ALS for 3 consecutive days caused extensive depletion of the paracortical areas of peripheral lymph nodes whereas treatment with normal serum and anti-lymphokine serum caused no such depletion. It is proposed that the anti-lymphokine serum is directed against activated lymphocyte products, one of them being MIF. These products are involved in the mediation of delayed hypersensitivity reactions. This is in marked contrast to ALS, the suppressive action of which appears to be central rather than peripheral.     

Surgical correction of burn deformities of the nose.

We present a method for reconstruction of the everted nostrils of the burned nose. Through a "ram's horn" incision, the everted vestibular lining and lower lateral cartilages are mobilized and repositioned, and the resultant defect is covered with a full-thickness skin graft. The linear scar is created as part of a circle, so that the postoperative contracture will improve the alar contour.     

Seborrhoea is not a feature of seborrhoeic dermatitis.

The sebum excretion rate from forehead skin was measured in 44 patients with classic seborrhoeic dermatitis and 200 control subjects. The mean excretion rate was normal in the 29 men with seborrhoeic dermatitis and significantly reduced in the 15 women with the disease. This study showed that seborrhoeic dermatitis is not usually associated with seborrhoea, and therefore "dermatitis of the sebaceous areas" may be a more accurate term.     

Representation of moving stimuli by somatosensory neurons.

The findings obtained in neurophysiological and psychophysical investigations using tactile stimuli that move at constant velocity across the skin are reviewed. For certain neurons in the postcentral gyrus of the cerebral cortex (S-I) of macaque monkeys, direction of stimulus motion is a "trigger feature" i.e., moving tactile stimuli evoke vigorous discharge activity in these neurons only if the stimuli are moved in a particular direction across the receptive field. This directional selectivity is maximal when stimulus velocity is between 5 and 50 cm/sec, and falls off rapidly at lower or higher velocities. The capacity for human subjects to correctly identify the direction of stimulus motion on the skin exhibits a similar dependence on stimulus velocity. The similar effects of velocity on neural and psychophysical measures of directional sensitivity support the idea that direction of stimulus motion on the skin can only be recognized if the moving stimulus optimally activates the group of S-I neurons for which that directions of simulus motion is the trigger feature.     

Collagenase of human skin basal cell epithelioma.

Collagenase of human basal cell epithelioma was purified by sequential ammonium sulfate precipitation, Sephadex gel filtration and affinity chromatography on collagen-polyacrylamide gel. The collagenase, when partially purified, was found to have an approximate molecular weight of 50,000. The purified enzyme contained no caseinolytic activity. On polyacrylamide gel electrophoresis, the purified enzyme gave a single protein band. The purified collagenase cleaved native acid-soluble guinea pig skin collagen at 37 degrees C with a pH optimum of 8. The enzyme was inhibited by EDTA, cysteine, and human serum but not by soybean trypsin inhibitor. Heparin did not stimulate the enzyme activity. Purified collagenase reduced the specific viscosity of native acid-soluble guinea pig skin collagen to 50 per cent of its original value at 27 degrees C. Polyacrylamide gel disc electrophoresis of the reaction products showed bands corresponding to alphaA, betaA, and alphaB fragments. Electron microscopic examination of SLS aggregates of the reaction products showed that the cleavage site by the enzyme was at a point 75 per cent from the "A" end (TCA75) and 25 per cent from the "B" end (TCB25) of the collagen molecule.     

Antigenic heterogeneity in patients with reactions in borderline leprosy.

Fifteen patients with borderline leprosy who developed "reversal" reactions were studied from the inception of treatment. Thirteen showed an appreciable increase in lymphocyte transformation (LT) when preparations of Mycobacterium leprae were used as antigen. The LT responses to either "whole" or "sonicated" preparations of the bacillus in these 15 patients and in nine others also in reaction correlated with the clinical presentation. Those with skin disease predominating in the reaction showed an appreciable increase in LT when whole M leprae was used as antigen. Those with nerve disease predominating showed an increase with sonicated M leprae. In those with both skin and nerve disease there was an increase with both antigen preparations. The ratios of the LT test results (whole to sonicated M leprae) showed highly significant differences between the three groups.     

Reconstruction of the oral mucocutaneous junction.

An inset free skin graft from the postauricular area was used to create a natural appearing "white roll" mucocutaneous junction in a lip repair.     

Cell-specific differences in membrane beta-glucosidase from normal and Gaucher cells.

Two isozymes of membrane-bound beta-glucosidase (beta-D-glucoside glucohydrolase, EC 3.2.1.21) with activity towards 4-methylumbelliferyl-beta-D-glucopyranoside have been identified in human cells. One of these isozymes was found to have a pH optimum of 5.0, a Km of 0.4 mM and to be rapidly inactivated at pH 4.0 ("acid-labile"). The second isozyme had a pH optimum of 4.5, a Km of 0.8 mM and was stable at pH 4.0 ("acid-stable"). Cultured long-term lymphoid lines and peripheral blood leukocytes contained both isozymes while cultured skin fibroblasts contained only the "acid-stable" form in detectable amounts. The specific activity of the "acid-stable" isozyme was severely reduced in cultured skin fibroblasts, cultured long-term lines and peripheral leukocytes from patients with Gaucher's disease. The specific activity of the "acid-labile" enzyme in the latter two cell types was apparently unaffected. The beta-glucosidase activity in all three cell types examined was predominantly particulate but the enzyme could be solubilized with low concentrations of Triton X-100. The solubilized enzyme required sodium taurocholate (0.2%) for maximum activity. Solubilized beta-glucosidase did not exhibit the cell-specific differences in pH optimum and Km shown by the membrane-bound enzyme.     

The ptotic (witch's) chin deformity: an excisional approach.

Ptosis of the chin pad is common and can be seen in patients of all ages. It may be associated with too little or (at times) too much anterior chin projection. Often there is an associated deep submental skin crease present. Frequently, the primary concern of the patient is the appearance or exaggeration of chin ptosis in smiling ("dynamic" ptosis). This report describes a flexible approach to the correction of developmental (and some iatrogenic) ptotic chin deformities. The key element in the approach is the direct excision of sagging or excess chin fat, muscle, and skin. No attempt is made to reposition or lift ptosis-prone soft tissues. If a deep submental skin crease is present, it too is excised. If the chin needs added anterior projection, it is accomplished with a stable alloplastic chin implant. The approach is uniquely suited to correct anterior overprojection caused by an excess of soft tissue at the front of the chin and has been successful in correcting the "dynamic" ptosis that appears with smiling.