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In this paper, a new contribution to the design of quartz crystal oscillators for high-sensitivity microbalance sensors used in liquid media is presented. The oscillation condition for a Miller configuration was studied to work in a wide dynamic range of the resonator losses. The equations relating the values of the active and passive components with the maximum supported damping and mass were obtained. Also, the conditions to obtain a stable frequency according to the resonator damping (R(Q)), the static capacity (Cp) and the filter frequency (f(F)) were found. Under these conditions, the circuit oscillation frequency will be proportional to the resonant series frequency and does not depend on the previous parameters (R(Q), f(F), and Cp). If these conditions cannot be satisfied, the expression of the oscillation frequency is given and the discrimination of these effects is obtained through resonator frequency measurements.

In the microelectronic industry using the damascene process, dendritic growth is observed on some parts of the circuits in critical conditions during the post-CMP cleaning step. To understand the electrochemical mechanism leading to this parasitic phenomenon copper behaviour in oxalic acid media was investigated by impedance measurement in both cathodic and anodic potential range and the dendritic growth conditions were studied.. Copper-oxalate complexes in the solution are taken into account.

Resume Propos. – Le lupus erythemateux dissemine revele chez des sujets âges a ete peu etudie (une serie de 21 patients de plus de 65 ans publiee). La prise en charge de cette maladie est-elle modifiee dans cette population ? Methodes. – Dix-sept cas de lupus ayant debute apres 65 ans et hospitalises entre 1988 et 2000 sont rapportes retrospectivement. Les resultats sont compares a ceux de sujets plus jeunes. Resultats. – Le sex-ratio femme/homme est a 1,83. L’âge moyen lors de la survenue du premier signe est de 71,9 ± 3,5 ans. La duree moyenne de suivi est de 3,5 ± 2,4 ans. Les principaux signes initiaux sont une alteration de l’etat general (41 %), des manifestations articulaires (35 %), cutanees (35 %), thromboemboliques (24 %) et des pleuresies (18 %). Le rash malaire est exceptionnel (12 %). La nephropathie n’est jamais revelatrice et rarement severe au cours de l’evolution. Comme pour les atteintes neurologiques, l’etiologie doit etre discutee en tenant compte des comorbidites. Sur le plan hematologique, la lymphopenie (82 % des patients) a une specificite contestable. Les anticorps antinucleaires sont constants, avec des anti-ADN natifs dans 82 % des cas, des anticorps anti-antigenes nucleaires solubles dans 50 %, un anticoagulant circulant dans 59 %. Le pronostic est difficile a estimer sur une petite serie, mais la probabilite de survie a 5 ans est de 83 %. La corticotherapie a entraine 50 % de complications graves. Conclusions. – Cette etude permet surtout d’insister sur les manifestations revelatrices particulieres du lupus erythemateux dissemine chez le sujet âge (alteration de l’etat general, thromboses, signes cutanes atypiques), ainsi que sur les difficultes specifiques du diagnostic differentiel et du traitement.

In this paper, basic principles of piezoelectric transducers are presented. Various systems are devised and a concrete example is exposed for direct biodetection with a 27 MHz QCM. Endly, recent and typical applications, using classical QCM for biosensing, are summarized.

Resume Le developpement des biocapteurs en general a ete stimule par le besoin d'analyse en temps reel, sans traitement prealable de l'echantillon et sans manipulation de produits dangereux. Parmi les systemes disponibles, la microbalance a quartz electrochimique est un dispositif prometteur car il permet l'analyse simultanee de deux parametres. La variation de masse est directement mesuree via la frequence de resonance du cristal et l'etat de surface du transducteur peut etre evalue, in situ, grâce a la mesure de l'impedance electrochimique. Le dispositif elabore peut etre utilise, d'une part, pour etudier les phenomenes d'adsorption ainsi que les interactions biomoleculaires et, d'autre part, comme un outil de detection quand la surface du transducteur est revetue d'anticorps.

Nowadays, immunosensors play a leading part in the field of bio-analytical chemistry research. As with any biosensor, they need appropriate transducers and a suitable technique to immobilize the active biocomponents. In this study, two transduction modes were chosen: mass effects (quartz microbalance measurements) and geometric and dielectric effects (capacitance measurements). The Langmuir-Blodgett (LB) method appears to be quite suitable for generating biospecific surfaces. This work has focused on the detection of staphylococcal enterotoxin B, the corresponding antibody being immobilized at the surface of fatty acids by a variant of the LB method. The composition of the film and the nature of antibody-fatty acid interactions were studied by means of the two transducers mentioned above, FTIR (Fourier transform infra-red) spectroscopy and protein diagnostic assay. Influence of several parameters (pH, ionic strength, transfer pressure, antibody concentration in the subphase) was investigated. The immobilization rate reached its maximum when experimental conditions allowed optimal electrostatic interactions. In this case, the quartz crystal microbalance response, in air, reached 55 Hz per monolayer of immobilized immunoglobulin G, and the equivalent capacitance variation, measured in liquid media, was around 300 pF cm−2. Activity of the biospecific LB films, when binding enterotoxin, was checked by the classical ELISA (enzyme immuno-linked assay) technique.

orange pericarp (orp) is a seedling lethal mutant of maize caused by mutations in the duplicate unlinked recessive loci orp1 and orp2. Mutant seedlings accumulate two tryptophan precursors, anthranilate and indole, suggesting a block in tryptophan biosynthesis. Results from feeding studies and enzyme assays indicate that the orp mutant is defective in tryptophan synthase beta activity. Thus, orp is one of only a few amino acid auxotrophic mutants to be characterized in plants. Two genes encoding tryptophan synthase beta were isolated from maize and sequenced. Both genes encode polypeptides with high homology to tryptophan synthase beta enzymes from other organisms. The cloned genes were mapped by restriction fragment length polymorphism analysis to approximately the same chromosomal locations as the genetically mapped factors orp1 and orp2. RNA analysis indicates that both genes are expressed in all tissues examined from normal plants. Together, the biochemical, genetic, and molecular data verify the identity of orp1 and orp2 as duplicate structural genes for the beta subunit of tryptophan synthase.

In order to graft a silicon nitride (Si3N4) pH-ISFET (ion-sensitive field effect transistor) for the preparation of a reference field effect transistor or an ion-sensitive Si3N4 ISFET, a preliminary oxidation treatment of Si3N4 thin layers has been followed by ellipsometry and X-ray photoelectron spectroscopy. The grafting of the oxidized Si3N4 has been tested with C22 alkylsilane. X-ray photoelectron spectra show the formation of a superficial silica (SiO2) layer whose thickness measured by spectroellipsometry depends on the oxidation conditions (atmosphere, time, temperature). The pH sensitivity of the oxidized Si/SiO2/Si3N4 structures is similar to that of SiO2. After C22 chemical grafting, the pH sensitivity is decreased to 20 mV pH−1.

SUMMARY The increasing availability and use of supercomputer s has highlighted the need for better software development techniques and tools. Supercomputers have traditionally been extensively used by engineers and scientists whose preference for Fortran is well established and recognized. However, in the parallel environment offered by the latest configurations of supercomputer s, more sophisticated languages and tools are required. The present experiment is concerned with devising a syntax-directe d integrated programming environment based on the language Actus, which enables a user to develop and debug programs before submitting them to an actual supercomputer. Actus is a high-level, Pascal-like language, with SIMD parallel processing features. It enables the user to ignore the idiosyncrasies of the chosen supercomputer by abstracting the parallel processing detail to a higher level. The editing, compilation and testing phases of program development are ail integrated, providing a single consistent interface for all activities relating to program development.

The feasibility of an Ag+-sensitive electrolyte—insulator—semiconductor field-effect transistor (EISFET) with silica surface modified by chemical grafting has been previously proved. Fabricated EISFET sensors feature a long lifetime and a fast response. The main purpose of this paper is to provide further insight into the chemical processes that govern the chemical sensitivity of an Ag+-sensitive EISFET sensor. A first order theoretical model is developed that allows the potential at the insulator—electrolyte interface, the threshold voltage potential and the gate voltage of an Ag+-sensitive EISFET sensor, with silica surface modified by chemical grafting, to be determined. The site-binding model has been applied to the modified silica/electrolyte interface. The model successfully explains the Ag+ sensitivity as well as the H+ ion interference effect on the EISFET as an Ag+ sensor. Some discussion of the parameters influencing the Ag+ sensitivity has been presented. From this model, it is concluded that the cyanografted site density, NsCN, and the complexation constant, p KCN, are the main controlling factors for the EISFET as an Ag+ sensor. For high sensitivity, large NsCN and p KCN values are required. This provides guideline for selecting a proper chemical grafting process to achieve improved Ag+ performance. In this study, a one-dimensional model with the insulator surface potential, Ψ0, assumed to be constant along the direction of the channel is used. The current—voltage (terminal) characteristic of the EISFET is then derived in a manner similar to the derivation of MISFET characteristics, in which Ψ0 is obtained by solving the system of equations for the EIS structure. The overall model is used to predict the manner in which the gate voltage varies with the Ag+ concentration. The presented model can be adapted to other ion-sensitive EISFET sensors.

Enzyme field effect transistors (ENFETs), which have been previously proposed for the detection of urea, consist of a pH ion-sensitive FET with urease enzyme immobilized in a polymeric membrane. A new means of preparing the enzymatic sensing layer is proposed in which urease is directly covalently bonded onto the silica insulator. The sensitivity, lifetime and response time of the ENFETs obtained are fairly good.

The quartz crystal oscillator used as mass sensor in damping media suffers significant losses implying the need to adapt the oscillator design to compensate them. In this paper, a CAD tool to help students in the understanding, design and optimization of Miller oscillators for the realization of high sensitivity quartz crystal microbalance (QCM) sensors for liquid media is presented. This tool is oriented not only to the practical teaching of advanced Thickness Shear Mode (TSM) acoustic wave sensors for mass changes detection, but also to aid designers in the development of QCM sensors.

Summary Background Hereditary subtotal leuconychia is a rare nail disease. The gene(s) underlying this phenotype is (are) not known. Immunohistochemical and ultrastructural studies of nails are performed infrequently. Objectives To perform genetic linkage analysis and to assess ultrastructure and soft/hard keratin expression in hereditary white nails. Methods We have analysed microscopically and ultrastructurally the white nails of a patient from a family in which the trait is inherited in an autosomal dominant manner as an isolated symptom. No skin lesions or hair abnormalities could be detected. Genetic linkage studies were performed on DNA samples obtained from several members of the affected family. A longitudinal surgical biopsy of the nail from a great toe was split in two parts. One part was fixed in formalin and processed for histopathology. Another part was further subdivided and embedded either in Epon, following fixation in 2% glutaraldehyde, or in Lowicryl K4M, after fixation in 3% paraformaldehyde. Dewaxed nail sections and Lowicryl ultrathin sections were also stained with various antikeratin antibodies. Results Genetic linkage studies of the family pointed to the disease gene mapping to the chromosomal 12q13 region. Genes mapping within this chromosomal region include the genes coding for type II (basic) cytokeratins and hard keratins. The nail matrix presented an abnormal hypergranulosis. The upper part of the nail plate, originating from the proximal nail matrix, had a nonhomogeneous lamellar appearance, with numerous intracellular ‘lipidic’ vacuoles and ‘empty’ spaces separating keratin filament bundles. These cells were progressively shed at the nail surface. The cell loss was compensated by hyperproliferation of the distal matrix and of the nail bed keratinocytes, with persistent marked parakeratosis and loose arrangement of keratin bundles. The distal matrix and the nail bed contributed equally to formation of the lower plate. This presented the characteristics of a tissue composed of soft keratins. Accordingly, there was virtually no labelling with the Hb1 antibody to a basic hard keratin in the white nail, whereas the labelling with AE3 antibody to all type II keratins and with KL1 recognizing suprabasal soft keratins was normal or even enhanced. Conclusions Genetic linkage indicates that the gene defect underlying the leuconychia in the family studied resides on chromosome 12q13. As the type II keratins map within this chromosomal interval, it is possible that a mutation in one of these keratin genes may be a cause of the hereditary leuconychia. The white appearance of nails in this disease seems to be due to an abnormal keratinization of cells originating from the proximal nail matrix, leading to the presence of abundant intracellular vacuoles and to a lesser compactness of keratins.

The quartz-crystal microbalance appears as an attractive tool for sensor applications. Indeed, a different response signal can be obtained: frequency variations occurring after various interactions are in general attributed to a mass variation. In fact, many factors can affect this response: viscosity, density, visco-elasticity, etc. Therefore, an impedance analysis of such piezoelectric transducers seems necessary in order to validate this tool. Preliminary results demonstrate the necessity of using a network analyser, in particular for viscosity interferences.

Dermal melanocytosis is characterized by the presence of ectopic melanocytes in the dermis. There are several clinical forms. This report describes an unusual case of acquired dermal melanocytosis probably associated with leptomeningeal melanosis. An ultrastructural study was performed.A 52-year-old Caucasian woman presented with a fifteen-year history of slowly spreading gray-blue macular pigmentation, associated with multiple blue nevi. Histologic examination revealed dermal melanocytosis. An extracellular sheath surrounded the melanocyte and their cytoplasmic processes. Medullar magnetic resonance findings were compatible with leptomeningeal melanosis.Dermal melanocytosis is thought to represent a disorder of neural crest migration. Melanocytes are thought to be aberrant and become arrested during migration, remaining in the dermis. Reactivation of latent dermal melanocytes should explain the pathogenesis of acquired forms. Ultrastructural examinations show an extracellular sheath enclosing dermal melanocytes in all types of dermal melanocytosis.

We report a 53-year-old woman who presented with multiple painful red cutaneous papules that had been growing slowly for 13 years. Histopathology showed typical features of neuroma. Biological, morphological and genetic investigations were negative and excluded the diagnosis of multiple endocrine neoplasia type 2b. After reviewing the literature, we concluded that our patient has an extremely unusual acquired disease, which must be considered as a distinct entity in the spectrum of cutaneous neurological disorders.

Biodetection is one of the most important challenges for the twenty-first century: many fields are concerned, mainly environmental and medical. The quartz crystal microbalance (QCM) may offer great possibilities for this purpose: a direct response signal, which characterizes the binding event between a sensitive layer, immobilized onto the surface transducer, and the analyte to be detected, can be obtained. However, for the detection of small biomolecules such as antigens, it is quite difficult to obtain an observable signal that corresponds directly to the binding event. In general, this is owing to the lack of mass sensitivity of the commonly used QCM, with 5- to 10-MHz quartz crystals. For improving this mass sensitivity, a 27-MHz quartz resonator was developed and incorporated in a flow-through microcell. Two biospecies, IgG rabbit and peroxidase enzyme, were studied with this ultra-sensitive QCM in terms of specificity, detection limit, and calibration curve.

A new episode of chicken pox in adults who had a well documented infection previously is usually observed in immunocompromised individuals. The principal immunodeficiency factors are hematology diseases, acquired immunodeficiency disease and old age. We report here the case of a young woman who after a contaminating contact presented a recurrence of typical chicken pox. Morphological investigations evidenced a right kidney tumor which pathology revealed to be a renal adenocarcinoma. We discuss this pathological association and review cases reported in the literature.

A 37-year-old man without previous medical history working as a lock keeper was seen in our unit for a progressive painless subcutaneous flesh coloured infiltration of the lower anterior area of the neck growing slowly over 5 months. Clinical cutaneous findings showed a non pruriginous yellowish papulonodular eruption mimicking xanthomas (Figs. 1 and 2). No other clinical abnormalities were found. A cutaneous biopsy specimen was performed. Histopathological examination revealed, under a normal epidermis, a dense lymphoplasmocytoid infiltrate involving the dermis with periadnexal and perivascular reinforcement (Figs. 3 and 4).

Peeling skin syndrome is a rare form of congenital ichthyosis. The term was coined in 1982 by Levy and Goldsmith and the syndrome is clinically characterized by generalized scaling. Histologically, there is an epidermal separation in the stratum corneum.We report the case of a 73-year-old woman who had ichthyosis without cicatricial progressive alopecia since her first pregnancy. An ultrastructural study was performed confirming the clinical diagnosis of peeling skin syndrome.The peeling skin syndrome designates several different clinical entities classed by Traupe in type A and type B. Mevorah and al. expanded this classification with a type C. This classification has remained valid after additional information provided by ultrastructural studies and may suggest different pathogenic mechanisms underlying the dermatosis. A critical review of the literature shows that the case reported here is exceptional and had a late clinical onset.

Epithelioid hemangioendothelioma described first by Weiss and Enzinger in 1982 is an uncommon vascular tumor usually involving soft tissue, less frequently the lung and the liver and exceptionally the skin. We herein report a 52-year-old woman who presented an isolated moderately painful persistant ulceration of the concha of her left ear. Histopathological findings showed strands and nests of epithelioid endothelial cells typical of cutaneous epithelioid hemangioendothelioma. Immunohistochemical stainings confirmed the vascular nature of the tumor. Surgical excision by ear amputation was performed. In a review of the literature, to our knowledge, this clinical presentation as ulceration has never previously been reported.

We report 2 cases of acquired lymphangiectasias after breast radiosurgical treatment. This well known, rarely reported complication is probably due to a mechanical obstruction of the lymphatic network, and is generally preceded by lymphedema. Our 2 cases, however, did not have previous lymphedema. After a review of the literature, we discuss the role of reparative surgery and other treatment options.

Kaposi's sarcoma associated with acquired immunodeficiency syndrome is uncommon in children and cutaneous localizations are rare. We report a case of pediatric cutaneous Kaposi's sarcoma that revealed a human immunodeficiency virus infection.An 8-years-old girl native of the Ivory Coast, with normal statural and psychomotor development, presented cutaneous Kaposi's sarcoma after varicella. The serodiagnosis was positive for type 1 human immunodeficiency virus and CD4 lymphocytes count was 9/mm3. A tonsil localization of Kaposi's sarcoma occurred and bleomycin was a short time effective. A relapse of cutaneous Kaposi's sarcoma with digestive, pulmonary and neurological symptoms was transitorily controlled by the association prednisone-vinblastine-doxorubicin, but death occurred with recurrence of pharyngeal Kaposi's sarcoma.The review of literature shows that in pediatric acquired immunodeficiency syndrome, failure to thrive, encephalopathy and opportunistic infections are common. On the other hand, Kaposi's sarcoma is unusual and cutaneous localizations are especially observed when the contamination is postnatal and late. In our case the contamination is presumed perinatal and the human immunodeficiency virus infection was asymptomatic until 8 years old. Kaposi's sarcoma was the cause of the most presenting symptoms and of death, without demonstrated opportunistic infections.

Although the hepatitis B vaccination tolerance is generally good, adverse effects, which are specially neurologic and cutaneous, have been observed and some cases of induced diseases with immunological disorders have been reported.A 6 year-old boy presented a cutaneous lupus erythematosus and a severe buccal aphthosis following hepatitis B vaccination. There was no clinical or biological symptom of systemic lupus erythematosus nor of Behçet's disease. Under chloroquine therapy, the cutaneous manifestations of lupus erythematosus disappeared quickly and those of buccal aphthosis improved.Hepatitis B vaccination side effects are probably in relation with a specific or non specific stimulation of the immune system. In our case, cellular immunity is perhaps involved through the HBs antigen. Considering the rarity of these side effects, an individual predisposition seems very likely.

Cutaneous involvement with Mycobacterium avium-intracellulare is usually observed in disseminated disease but cutaneous infection alone without bacteraemia is uncommon.We report a case of Mycobacterium avium-intracellulare subcutaneous abscess of the thigh in a 32-year-old woman with lymphoma. The lesion was treated with drainage, excision and chemotherapeutic agents. Inoculation was probably secondary to alpha interferon injections performed during one year.The review of the literature shows that isolated Mycobacterium avium-intracellulare skin infections are rare, probably induced by traumatic percutaneous inoculation, frequently in immunocompromised patients. The pro-infectious effect of interferon alpha is considered. Treatment is unsatisfactory and surgical excision is often necessary.

We are reporting a case of allergy to celery, having brought on an urticaria-oedema-anaphylactic shock. It is an interesting case due to the chronology of the clinical manifestations and crossed reactions with parsley, carrot and ragweed and equally the participation of several organs: skin, alimentary tract, lungs.

Albright's hereditary osteodystrophy has been diagnosed in a 35-year-old woman who presented recurrent cutaneous ossifications of the auricular area. The patient exhibited other cutaneous ossifications, a short stature with obesity, round face, stocky hands and feet, radiological calcifications of the skull and of the hands, cataract, auditive impairment and dental abnormalities. Serum calcium, phosphorus and parathyroid hormone levels were normal. Urine excretion of phosphorus and cyclic adenosine monophosphate (cAMP) markedly increased after intravenous injection of parathyroid hormone, referring to pseudopseudohypoparathyroidism. Albright's hereditary osteodystrophy is associated either with pseudohypoparathyroidism type 1a characterized by parathyroid hormone and other hormones resistance or with pseudopseudohypoparathyroidism without hormone resistance. This two conditions are considered variants of the same defect of the stimulatory G protein of adenylate cyclase which is necessary for the action of parathyroid hormone, and other hormones to use cAMP as an intracellular second messenger. But Albright's hereditary osteodystrophy may be associated with other biochemical abnormalities, such as defect of catalytic activity of adenylate cyclase in pseudohypoparathyroidism type 1c. There is an important variability of the clinical, biochemical and genetical expression of pseudohypoparathyroidism and today classification is provisional.

Verruciform xanthoma (VX) usually occurs within the oral cavity, rarely in the genital areas. A case of VX on uncircumcised penis is reported in a 58 year-old man without prior history of sexual transmitted disease; histological features are characteristic and staining of the foam cells are positive with CD68 and negative with S100 protein. Etiological factors of the VX are uncertain and in the genital localizations a viral cause has not been proved.

The pl gene encodes a regulatory protein that controls the transcription of a number of structural genes of the anthocyanin biosynthetic pathway in maize. pl alleles have been classified phenotypically into two categories: dominant (Pl) alleles lead to intense, light-independent pigmentation in vegetative and floral organs of the plant; recessive "sun-red" alleles (pl) lead to light-dependent red pigmentation in which only tissues exposed to light become pigmented. Based on these observations, two alternate pathways leading to anthocyanin synthesis in the plant have been proposed: one requiring light and the other bypassing the light requirement through the action of Pl. To evaluate this hypothesis, we have analyzed light-independent and light-dependent alleles of pl. Sequence analysis revealed that the two types of alleles have very distinct promoters but have the capacity to encode very similar proteins. The protein encoded by one recessive allele was shown to be functional in transient assays. Measurements of husk mRNA levels by quantitative polymerase chain reaction showed that sun-red pl alleles are expressed at much lower levels than a Pl allele, but their expression is increased approximately sixfold by exposure to light. These results lead to the conclusion that the sun-red pl alleles are not null; instead, they synthesize functional mRNA and protein. We propose that the light-dependent pigmentation observed in pl plants is the result of a threshold effect in which light exposure boosts pl mRNA expression past a crucial level necessary to generate sufficient PL protein molecules to activate transcription of the anthocyanin structural genes.

We report a new case of successful liver transplantation in a 36-year-old patient with terminal hepatic failure due to erythropoietic protoporphyria. Data regarding protoporphyrin levels in erythrocytes and feces, before and after transplantation, seem to indicate that in this case protoporphyrin overproduction was in part due to liver synthesis. Four years after surgery, the patient is completely free of skin photosensitivity. His liver function tests are normal; there are no visible protoporphyrin deposits or ultrastructural abnormalities in his new liver. However, recurrence of the disease in the long term cannot be excluded, since erythrocyte protoporphyrin levels remained elevated after liver transplantation.

A case of non-actinic disseminated superficial porokeratosis with dermal amyloid deposits in a 53 year-old-man is reported. The lesions of the trunk and arms were typical, but annular lesions of the ankles were lichenoid. The amyloid deposits were present under the cornoid lamella in the typical lesions and absent in the annular lesions. The different clinical variants of porokeratosis are discussed. The origin of amyloidosis is debated; it seems to be epidermic, due to degeneration of the keratinocytes. The secondary cutaneous amyloidosis is usually described in association with epithelial tumors or psoriasis, but exceptionally with porokeratosis.

A new method of thin layer chromatography was used for the study of faecal porphyrins in 31 porphyric patients (20 cases of porphyria cutanea tarda, 5 cases of porphyria variegata, 2 cases of hereditary coproporphyria, 1 case of acute intermittent porphyria and 3 cases of erythropoietic protoporphyria), 14 of their clinically normal relatives and 5 controls. The pattern obtained was characteristic of each type of porphyria and compared to previously published data.

Pigmentation in a Causasian male, resulting from bleomycin therapy for Hodgkin's disease, has been studied ultrastructurally. The melanocytes, though present in normal numbers, showed several abnormalities; the endoplasmic reticulum and the Golgi apparatus were were well developed and the mitochondria were enlarged. Lipid inclusions in the endoplasmic reticulum and numerous autophagocytic vacuoles, some containing lipids were observed. Transfer of melanosomes to keratinocytes appeared to be increased. The melanosomes, which measured less than 0.55 mu were dispersed in the cytoplasm and did not form complexes, as has been observed with nitrogen mustard. The increase of melanocytic activity and the disturbance of melanosome transfer are discussed.

The possibility of obtaining ion-selective membranes on ISFETs by chemical grafting of the silica insulator has been previously shown. The grafting only slightly modifies the electrical characteristics of the transistor (the dielectric permitivity and thickness being nearly unchanged), which makes it possible to perform differential measurements between an ion-sensitive FET and a reference FET. For the detection of silver ions, the sensitive membrane (dimethylamino)silane onto silicon dioxide; the reference FET is an ISFET fabricated by grafting an aliphatic chain onto silicon dioxide. The response obtained, i.e., the difference between both source potentials versus a platinum pseudo-reference electrode, can be described with the site binding model. The differential method allows a miniaturized reference electrode to be used. At the same time, the effects of drift, temperature and residual pH response are reduced.

Summary Studies of both hypermelanosis and hypomelanosis in six patients with generalized scleroderma and in two patients with localized scleroderma were performed. Examination of epidermal split dopa preparations showed an absence of dopa positive melanocytes in depigmented skin, a reduction in hypopigmented skin in which the cells were elongated, bipolar or comma-shaped, and a normal population in hyperpigmented skin, in which the melanocytes were larger, with prominent dendrites, and exhibited intense enzyme reactivity. Ultrastructural studies confirmed the disappearance of melanocytes in depigmented skin. In hypopigmented skin, the melanocytes contained few melanosomes and showed evidence of cytoplasmic degeneration (lipid vacuoles and autophagocytosis of melanosomes). In hyperpigmenred skin synthesis of melanosomes and their transfer to neighbouring keratinocytes was increased. Melanosome autophagocytosis was also observed in these specimens. No significant differences in melanosome size was found between hyperpigmented, hypopigmented or healthy skin. Hypermelanosis associated with scleroderma is due to increased activity of epidermal melanocytes and hypomelanosis is attributable to the disappearance of melanocytes.