Immunoglobulins coat microorganisms of skin surface: a comparative immunohistochemical and ultrastructural study of cutaneous and oral microbial symbionts.

Only recently have human sweat glands been demonstrated to secrete immunoglobulins (Ig), paralleling Ig secretion in mucosal epithelia. It is well established that Ig protect mucosal membranes against infections by binding to surface structures of microorganisms. In view of these findings immunohistochemical studies were performed to determine if microbes on the skin surface are coated by Ig as proposed for mucosal bacteria and fungi. Smear preparations from the skin and oral cavity rich in micro-organisms were subjected to immunoperoxidase staining using anti-secretory component (SC), -IgA, -IgM, -IgG antibodies. An immunogold labeling technique of microbial suspensions of sweat and saliva was adapted to correlate the results on an ultrastructural level. Negative controls included unsuccessful staining for IgA in preparations obtained from an IgA-deficient patient as well as nonreactivity of subcultured microorganisms for all Ig classes or SC. Smear preparations from both the oral cavity and skin surface exhibited labeling of bacterial or fungal elements with anti-IgA, -IgM, -IgG, and -SC antibodies. Skin bacteria revealed a lower number of reactive microbes as compared to saliva. Staining intensity for the different Ig classes exhibited intra- and interindividual variations. Immunoelectronmicroscopically, Ig and SC could be detected either directly along the cell wall of coccal, coryneform, and fungal elements or on floccular and fimbrial material adhering to the bacterial surface. It is concluded that secretory Ig of the skin cover surface structures of microorganisms and thus modify their adhesional and/or infectious properties, resembling humoral surface immunity on mucous membranes.

Comparative histochemistry of port-wine stains after copper vapor laser (578 nm) and argon laser treatment.

The present study compared the histologic changes occurring 15 min after copper vapor laser (CVL; operating at 578 nm) and argon laser (488/514 nm) treatment of port-wine stains (PWS) over a range of energy densities (8-32 J/cm2) with corresponding pulse widths of 50-200 ms. Frozen tissue sections were stained with nitroblue tetrazolium chloride (NBTC). This histochemical method permits an accurate color differentiation between blue-stained viable and unstained thermally damaged cells. At 8, 10, and 12 J/cm2 the argon-laser injury was confined to epidermal cell layers; none to superficial dermal effects were found. Fluences of at least 15 J/cm2 produced a diffuse NBTC-negative coagulation necrosis. Exposure of PWS skin to 8-12 J/cm2 at 578 nm did not alter the integrity of epidermal cells. In the dermis, damage was confined to blood vessels and surrounding collagen, showing a clear demarcation from adjacent viable structures. The maximum penetration depth achieved with these vessel selective energy densities was 0.44 mm. At 15 J/cm2, besides vascular injury, damage to the basal cell layer also occurred. At fluences of 17-20 J/cm2 a diffuse necrosis similar to that induced by the argon laser was found. Vessel selectivity of the 578 nm wave band was achieved with pulse widths from 50-74 ms, exceeding the estimated "ideal" exposure time (0.1-10.0 ms) for a vascular selective laser effect. The NBTC method allowed identification of subtle laser-induced tissue changes providing accurate quantitative data relating to the extent of vascular injury.

Immunohistochemical demonstration of immunoglobulin A in human sebaceous and sweat glands.

Immunoglobulin A (IgA) mediated humoral defense mechanisms have been detected on all mucous membrane surfaces. There are only a few papers about the presence of IgA in human skin. In order to demonstrate the occurrence of IgA in sebaceous and sweat glands, biopsies of normal human skin were investigated and compared to intestinal mucosa. Two different commercially available anti-IgA antibodies were used. For light microscopy peroxidase-anti-peroxidase (PAP) or avidin-biotin complex (ABC) staining was used, and for electron microscopy protein-A-gold (PAG) labeling was performed on tissue sections. Specifically decorated IgA was found in sebaceous glands as well as in various portions of eccrine glands. In sebaceous glands, the maximum of IgA concentration was seen near the mouth of pilosebaceous ducts. Sweat ducts exhibited a continuous coat of IgA, whereas secretory portions contained only singular scattered IgA positive cells. Immunoelectron microscopy suggests endocytotic uptake and processing of IgA in the glandular cells. These results indicate strongly that IgA are secreted by normal human sebaceous and sweat glands. Because it is well known that IgA plays an important role in inactivation of invading viruses, bacteria, and other antigenic structures on mucous membranes, it appears that IgA in sebum and sweat fulfil a similar function on the outer body surface.

A case of 'smouldering' mastocytosis with high mast cell burden, monoclonal myeloid cells, and C-KIT mutation Asp-816-Val.

Mastocytosis is a term used for a group of disorders characterized by abnormal growth and accumulation of tissue mast cells (MC) in one or more organ systems. In patients with systemic mastocytosis (SM) the clinical course may be indolent or aggressive or even complicated by leukemic progression or an associated clonal hematologic non mast cell lineage disease (AHNMD). However, at first presentation (diagnosis) it may be difficult to define the category of disease and the prognosis. We report on a 48-year-old female patient with SM with urticaria pigmentosa-like skin lesions and mediator-related symptoms. She was found to have splenomegaly, a high infiltration grade (MC) in bone marrow biopsies (>30%), mild anemia, and a high serum tryptase level (>500 ng/ml). In addition, she exhibited discrete histologic signs of myeloproliferation in the 'non-affected' marrow and monoclonal blood cells established by C-KIT 2468A-->T mutation (Asp-816-Val) -analysis and HUMARA assay. Despite these findings, however, the clinical course was stable over years and no AHNMD or organ impairment developed. Because of the 'intermediate' clinical signs and absence of progression to aggressive disease, we proposed the term 'smouldering mastocytosis'.

Myocardial revascularization in patients with chronic renal failure.

Symptomatic coronary artery disease in patients with chronic renal failure can complicate their management in a dialysis program. Hypotension associated with hemodialysis and the anemia of chronic renal disease can produce anginal episodes refractory to medical management. Untreated coronary artery disease may be a contraindication to renal transplantation in an otherwise acceptable candidate. We have encountered three cases of coronary artery disease severe enough to necessitate coronary bypass in patients from our long-term hemodialysis program. All three patients had uncomplicated postoperative courses, none had perioperative infarction, and in all three patients postoperative angiography demonstrated patency of all grafts. One patient subsequently underwent successful renal transplantation; the other two patients have continued in hemodialyses since bypass. We believe our experience and the reported experience of others confirm the feasibility of coronary bypass grafting in patients with chronic renal failure.

The relation of nervous elements to intradermal nevi. As electron microscopic study.

Intratumoral nerves of dermal nevi were investigated by electron microscopy in order to elucidate the role of neural elements in the development of these tumors. The following results were obtained: 1. Intratumoral nerves exhibit an increased cellularity, but the number of myelinated fibers is reduced. 2. Nevus cells type B and C are frequently present within nerve fascicles. 3. Unmyelinated axons were found in close relationship to nevus cells. 4. Schwann cells may show proliferations similar to early stages of neurofibroma and can be differentiated from unpigmented tumor cells by their relation to axons only. These findings indicate that identical cell populations are present within the intratumoral nerves and the tumor itself. Therefore, the theory of a neural component in the histogenesis of intradermal nevi is supported.

Hydroxyethylstarch deposits in human skin--a model for pruritus?

Severe itching for unknown reasons has been reported after administration of hydroxyethylstarch (HES) in haemodilution therapy of humans. After HES treatment, vacuoles in cells of various organs in humans have been shown, predominantly affecting the mononuclear phagocyte system. These vacuoles present indirect evidence for phagocytosis of HES particles. Since phagocytosis is also known to occur in the skin, this organ might represent a target for HES deposition, resulting in subsequent release of mediators responsible for the observed itching. The aim of the present investigation was to study skin biopsies of patients, who had received HES and suffered subsequently from itch. Skin sections were investigated for morphological impairment by means of light and electron microscopy, immunohistochemistry and immunoelectron microscopy using a polyclonal anti-HES antiserum. Storage of HES was demonstrated in the skin of all patients, mainly in dermal macrophages, endothelial cells of blood and lymph vessels, some perineural cells and endoneural macrophages of larger nerve fascicles, some keratinocytes and Langerhans cells. Treatment with antihistaminic agents proved ineffective in these patients; this fits with the observation that morphological signs of histamine release from mast cells were absent. These findings indicate that other mediators from HES-affected cells must be responsible for the development of the itching. Thus, investigation of HES storage may be a useful contribution to the elucidation of release of itch mediators and induction of pruritus.

[Stress ulcer-an experimental study (author's transl)]. / Das Stressulkus-eine experimentelle Studie.

This experimental study demonstrates by means of electromagnetic flow measurements that hypovolaemic shock results in a significant decrease in gastric flow. 14 mongrel dogs were subjected to haemorrhagic shock for 3 or 4 hours. Significant histological changes are seen in the gastric mucosa as a result of the haemodynamic changes, especially when the duration of shock was 4 hours. All stages of stress ulcer from the superficial erosion to deep ulcers were documented. The possibility that the mast cell plays a pathogenetic role as mediator in the origination of a stress ulcer is considered.

[Penicillamine-induced elastosis perforans serpiginosa and pulmonary cyst in Wilson's disease (author's transl)]. / Penicillamin-induzierte Elastosis perforans serpiginosa mit Lungenzyste bei Morbus Wilson.

A large air cyst was removed from the right lung of a 29-year-old female patient with Wilson's disease and penicillamine-induced perforating elastosis, the cyst first appearing after 9 years of treatment with penicillamine. Since, on the one hand, the microscopic and ultrastructural changes in the elastic tissue of the lungs were identical to those observed in the skin, both in areas of clinically-demonstrable elastosis perforans serpiginosa and clinically unaffected skin and, on the other hand, no other pulmonary disease was demonstrable to account for the development of the cystic lesion, it is concluded that penicillamine is the causative factor by means of extensive alteration of the elastic tissue. The morphological changes in the elastic fibres are so characteristic that it is easy to distinguish penicillamine-induced elastosis perforans serpiginosa from the idiopathic variant.

[Immunoglobulin A in the sebaceous glands. Light and electron microscopy immunomorphologic detection]. / Immunoglobulin A in Talgdrüsen. Licht- und elektronenmikroskopischer immunmorphologischer Nachweis.

This paper presents evidence for the presence of immunoglobulin A in human sebaceous glands. Light- and electron-microscopic immune cytochemistry techniques revealed secretory IgA in normal sebocytes and within pilosebaceous ducts. The secretory process corresponds to the well-established production of IgA at the site of other internal body surfaces. Basal and suprabasal sebocytes contain IgA in linear extracellular, as well as aggregated intracellular patterns. However, maximal diffuse concentrations are present at the opening of the pilosebaceous duct. This distribution pattern indicates an antimicrobial protective character of IgA, corresponding to similar functions on mucous membrane surfaces. Thus, another important humoral factor contributing to the complex system of skin-associated lymphoid tissue is postulated.

[NK cells and the nervous system]. / NK-Zellen und Nervensystem.

Light- and electron-microscopic studies of human, mouse, rat and guinea pig tissue subjected to PAP and ABC immune reactions revealed, that a monoclonal antibody against human natural killer cells (LEU 7) reacted also specifically with neural elements. In man, not only NK cells, but also myelin sheaths, oligodendrocytes, neurones, astroglial and ependymal cells as well as some enterochromaffin cells were labelled. Similar results, with the exception of negative ependymal cells, were obtained in the laboratory animals investigated. Controls and experiments using another monoclonal antibody against human natural killer cells (VEP 13) were negative. The presence of an antigen shared by human natural killer cells and neural elements could be of importance for the pathogenesis of demyelinating disorders.

[The leopard syndrome, a cardio-cutaneous syndrome]. / Das Leopardsyndrom, ein kardiokutanes Syndrom.

A patient with the "leopard" syndrome presented with cardiomyopathy and a large arteriovenous shunt of the left renal vessels. The skin manifestations included multiple lentigines, junctional naevi, blue naevi, and one malignant lentigo. This syndrome is a rare entity, but in all patients with multiple lentigines the possibility of associated cardiovascular changes should be considered. In addition, regular monitoring of the pigmented lesions should be performed because of the increased risk of development of malignant melanoma.

[Oculodermal melanocytosis (nevus of ota) and blue nevus (author's transl)]. / Okulodermale Melanozytose (Nävus Ota) und blauer Nävus.

Report is made of a patient having concurrently an Ota nevus and a blue nevus. The dermal melanocytes showed a marked formation of large intracytoplasmatic vacuoles. Reference to the important role of an "extracellular sheath" is made. The nearly identical ultrastructural characteristics of dermal melanocytes in various dermal melanocyte disorders seems to imply a common pathological origin in their development.

[Genital Chlamydia infections in female patients at risk of having sexually transmitted diseases]. / Genitale Chlamydieninfektionen bei STD- (= Sexually transmitted diseases-) Risikopatientinnen.

Investigations for Chlamydia infections of the genital tract were performed in 270 Viennese registered, as well as in 51 non-registered prostitutes. The results were compared with findings obtained in 56 female patients attending an out-patient STD clinic and 48 pregnant women seeking antenatal care in a department of obstetrics. Diagnosis of Chlamydia infection was the organisms on cultured McCoy cells after treatment with cycloheximide. The highest infection rate (31%) was found in non-licensed prostitutes. In registered prostitutes, 20.4% of the cervical smears proved to be positive for Chlamydia. The control groups showed lower infection rates of 9% and 4%, respectively. These results indicate that women who frequently change their sexual partners are considerably more at risk of contracting Chlamydia infections. Hence, this group of persons should be more regularly investigated and--if necessary--given appropriate treatment in order to prevent further spread of the disease.

[Mucopolysaccharidosis V (Ullrich-Scheie syndrome) (author's transl)]. / Mukopolysaccharidose V, Morbus ullrich-Scheie.

Mucopolysaccharidosis V (Scheie's syndrome, MPS-IS) is a very rare, autosomal recessively inherited metabolic disease. The degradation of dermatan sulphate and heparan sulphate is disturbed due to alpha-L-iduronidase deficiency, leading to intracellular storage and excessive urinary secretion of these substances. The characteristic clinical features are contractures (claw-like flexion of the fingers), umbilical and inguinal herniae, corneal opacity, hepatomegaly, myocardiopathy and minor skeletal malformations. A patient with Scheie's syndrome is now reported for the first time in Austria; the results of the clinical, biochemical, chromosomal, dermatoglyphic and electron optical investigations are described and discussed.

Physical changes of amniotic membranes through glycerolization for the use as an epidermal substitute. Light and electron microscopic studies.

Our Department of Plastic and Reconstructive Surgery has routinely been using amnion preserved in glycerol for the treatment of debrided II degrees burns. This treatment is almost pain free and requires fewer changes of dressings and fewer anaesthetics. It also prevents overgrowing granulation tissue and lessens scarring.Since 1910 amnion has been used as biological wound dressing. Its advantages such as reduced loss of protein and electrolytes, fluids and energy as well as reducing the risk of infection and accelerated regeneration of the epithelium have been well documented in medical literature.In order to more closely examine the question of possible changes to the micro structure of the amnion through preservation and rehydration as well as the interaction between transplanted tissue and recipient, we have carried out several light and electron microscopic studies.Results showed that neither the treatment with glycerol, nor the pretransplantation rehydration eliminates the monolayer of surface epithelium of the amnion. Its complex architecture remains intact during the preservation process and is therefore suitable as a matrix for the growth of keratinocytes and thereby the healing process.In clinical use we found amnion to be an excellent wound dressing as it allows proper control of fluid, has sufficient permeability for gases, has good thermal properties, is impervious to micro-organisms and is free from toxic material.

[Cytoid bodies in human skin (author's transl)]. / Zytoide Körperchen in der menschlichen Haut

Cytoid bodies represent ovoid, round or polygonal, approximately cellsized structures. In human skin such bodies may occur under normal as well as under pathological conditions. A number of heterogenous materials contribute to the morphogenesis of cytoid bodies, but in sections of human skin prepared for routine histology, different groups of cytoid bodies can not always be distinguished from each other. However, such a differentiation is necessary, if their presence is to be utilized as a diagnostic parameter or interpreted as a sign of physiological or pathological events in the dermoepidermal junction area. The object of the present studies was to (i) characterize the different groups of cytoid bodies by histological, histochemical, immunological and electron microscopical techniques, (ii) elucidate their nature, origin and morphogenesis and (iii) determine their significance in the histology of the skin. The following results were obtained: (1) Elastic globes can easily be identified by their bright autofluorescence and their affinity for elastin stains. Electron microscopically they exhibit a mixture of amorphous, granular and filamentous material, thus showing simlarities with elastic fibers. They are regularly found in normal skin of the extremities and the face but usually are absent on the trunk. Therefore their demonstration may be of importance in forensic medicine by allowing a better determination of the origin of isolated skin pieces. (2) Russel bodies may show gross variations in their histological, histochemical and ultrastructural properties. They contain different amounts of carbohydrates, lipids, proteins and immunoglobulins. These variable component result in a polymorphous structure. Russel bodies are produced by plasma cells and can frequently be found in skin infiltrates with a predominant admixture of this cell type. Their presence may be correlated with an increased local production of immunoglobulins, but their differentiation from other cytoid bodies and fungal elements is also of importance. (3) Civatte bodies are also eosinophil, PAS-positive and exhibit a typical fibrillar ultrastructure. They may be localised intraepidermally as well as in the upper corium. Although most frequently ecountered in lichen planus they may also be found in numerous other dermatoses and even in clinically normal skin. As indicated by their characteristics, they originate from epidermal keratinocytes and probably represent a morphological substrate of "apoptosis". (4) Amyloid is identified by the green birefringence of Congo red stained sections and by the more irregular arrangement of the individual filaments under the electron microscope. Cytoid aggregates of amyloid in the skin occur mainly in lichen amyloidosus and macular amyloidosis. Their presence should prompt further investigations of the patient for other signs of amyloidosis. (5) Fibrin in the form of cytoid clumps and clusters can frequently and specifically be demonstrated in skin diseases by immunofluorescence...

[Transient acantholytic dermatosis (Grover) (author's transl)]. / Dermatose acantholytique transitoire (Grover).

In this report, we wish to demonstrate histological and ultrastructural characteristics of transient acantholytic dermatosis, first described in 1970 by Grover. Papules on the upper part of the body and on the arms and thighs are noted in our two patients. They are small in size (2-4 mm) and encircled by an erythematous border; pruritus and vesicles with serous content are often present. The vesicles are follicular and tend to group. Biological and immunological studies are normal. Histological examination shows acantholysis and intraepidermal vesicles above which is hyperkeratosis with parakeratosis. In the dermis, inflammatory infiltrates are noted. Ultrastructural study reveals rarefaction of desmosomes and widening of intercellular spaces. Fragments of tonofibrils are also noted. Karyolysis is sometimes present. The dermis contains A. Civatte's bodies. It is likely that this recently identified disease is less unfrequent than it appears to be.