bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Primary Cultures and Vibrodissociated Cells as Tools for the Study of Astroglial Properties and Functions
Authors: Hansson Elisabeth , Thorlin Thorleif
Published: April 2003

The glial cells, especially the astroglia constitute a prominent part of the brain cell volume. Astroglial properties are difficult to study in the intact nervous system. For that reason, different in vitro models have been developed. The development of cell and tissue cultivation conditions has been the prerequisite to our present knowledge of the biochemistry and pharmacology of glial cells and to some extent even neurons. It is, however, an advantage if results from tissue culture can be evaluated in more in vivo like systems. We here describe a method for acute isolation of freshly prepared neurons and glial cells.
Differential Expression of Serotonin 5-HT2 Receptors during Rat Embryogenesis
Authors: Wu Chun , Dias Peter , Kumar Shant , Lauder Jean M. , Singh Sujay
Published: April 2003

Serotonin (5-HT) is a neurotransmitter that also functions as a hormone and a growth factor. 5-HT is involved in numerous physiological actions and displays complex pharmacological properties. As a growth factor, 5-HT plays a role in cell proliferation and differentiation of neuronal and nonneuronal tissue and it transduces its signals through more than fourteen subtypes of 5-HT receptors. Since determination of the expression and distribution is important for understanding the role of the 5-HT receptors, we have developed an RNase protection assay (RPA) that allows the simultaneous analysis of 5-HT2AR, 5-HT2BR, and 5-HT2CR per sample of RNA. This multiprobe set also comprises probes for two house-keeping genes, L32 and GAPDH, which control for sample-loading errors. Using this RPA probe set, we have examined the relative expression of 5-HT2AR, 5-HT2BR, and 5-HT2CR in rat embryos inclusively from embryonic day (ED) 9 to 21 of development. Our data indicate that 5-HT2AR levels gradually increased from ED11 to ED21. The expression of 5-HT2BR was decreased between ED9 to ED11 then remained relatively constant through ED21. 5-HT2CR was initially expressed at residual levels between ED9 and ED12 but dramatically increased to a peak level at ED13, then decreased by ED17. Expression of the 5-HT2 receptors in these tissues was confirmed independently by RT-PCR indicating that there is developmental regulation in the expression of these receptors. The 5-HT2R multiprobe assay will be useful for detecting relative changes in the expression of these receptors in developmental, normal and pathological tissues as well as for monitoring relative changes in expression resulting from the use of pharmaceutical agents.
The Neuroprotective Effects of Non-NMDA Antagonists in the Cerebellum of the spastic Han Wistar Mutant
Authors: Nisim A.A. , Hernandez C.M. , Cohen R.W.
Published: April 2003

Excitotoxicity resulting from the dysfunction of glutamate receptors has been attributed to neurodegeneration seen in many brain disorders. In our laboratory, the spastic Han Wistar mutant is currently utilized as a potential model of excitotoxicity. The mutant is characterized by progressive neuronal degeneration, hindlimb paresis and ataxia which culminates in the animal’s death at approximately 65 days of age. In this study, neuroprotection derived from acute administration of the non-NMDA antagonist GYKI 52466, and chronic administration of the non-NMDA antagonist CNQX was examined in order to determine the potential roles of non-NMDA receptors in the observed neurodegeneration. Mutants injected with GYKI 52466 (15 mg/kg), twice a week for 3 weeks, exhibited increased life spans (14%) and extended motor activity than their vehicle-treated mutant siblings. In a separate group of mutants, CNQX (either 50 or 500 μM) was infused directly into the third ventricle of the mutant’s brain utilizing osmotic pumps. A statistically significant increase in motor activity (22%) was detected for mutants treated with a dose of 50 μM CNQX compared to their vehicle-treated siblings. Finally, cerebellar histological evaluations of mutants treated with both 50 and 500 μM CNQX showed dose-dependent higher cerebellar Purkinje cell counts. These findings suggest that non-NMDA receptors play a significant role in neurodegeneration in this animal.
Selective Apoptosis Within the Rat Subependymal Zone: A Plausible Mechanism for Determining Which Lineages Develop from Neural Stem Cells
Authors: Levison Steven W. , Rothstein Raymond P. , Brazel Christine Y. , Young Greg M. , Albrecht Phillip J.
Published: April 2003

During development, the output of the subventricular zone (SZ) becomes increasingly restricted, yet it still harbors multipotential progenitors. The output of the SZ could be gated by selectively eliminating inappropriately specified progenitors. Using in situ end-labeling (ISEL) to identify apoptotic cells, nearly 60% of the ISEL+ cells in the juvenile forebrain were localized to the SZ. Of these dying cells, at least 9% could be identified as neurons, 4% as astrocytes, and 12% as oligodendrocytes. The remainder were negative for the stem cell marker nestin, as well as other markers evaluated. To test the hypothesis that committed progenitors were under selective pressures, neural stem/progenitor cells were allowed to differentiate in vitro in the presence or absence of the caspase 3 inhibitor z-DEVD-fmk. DEVD increased neuronal production 10-fold over control cultures. By contrast, the development of astrocytes and oligodendrocytes was not affected. Altogether, these data support the hypothesis that selective forces within the postnatal rat forebrain control the types of precursors that emerge from the germinal matrix. Furthermore, they suggest that different mechanisms control neuronal versus glial cell numbers.
Independent Controls for Neocortical Neuron Production and Histogenetic Cell Death
Authors: Verney C. , Takahashi T. , Bhide P.G. , Nowakowski R.S. , Caviness Jr. V.S.
Published: April 2003

We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm2 was calculated and the proportionate cell death for each day of the 2-week interval was estimated. The data show that cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the ‘inside-out’ neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity.
Characterization and Distribution of a New Cell Surface Marker of Neuronal Precursors
Authors: Schubert William , Coskun Volkan , Tahmina Mujtaba , Rao Mahendra S. , Luskin Marla B. , Kaprielian Zaven
Published: April 2003

In a screen for novel cell surface markers of neuronal progenitors, we recently identified mAb 2F7 that recognizes an epitope present on both progenitor cells and postmitotic neurons, in the developing CNS and PNS. In the embryonic rat telencephalon, the mAb 2F7 epitope is expressed by migratory and postmigratory neurons in the developing cerebral cortex, as well as by presumptive neuronal progenitor cells of the ventricular zone. In the neonatal forebrain mAb 2F7 labels postmitotic neurons, including those of the developing cerebral cortex and olfactory bulb, as well as the axons of the corpus callosum. While mAb 2F7 immunoreactivity is present on only a low density of the neuronal progenitor cells situated in the anterior part of the subventricular zone, a progressively higher proportion of cells forming the rostral migratory stream express this epitope. mAb 2F7 labels the surfaces of neurons and neuronal precursors, but not mature oligodendrocytes and astrocytes in primary cultures derived from the rat neural tube. In vivo, migrating neural crest cells, motor neurons, and axonal projections associated with the spinal cord express the mAb 2F7 epitope. Immunoblot analyses reveal that the mAb 2F7 epitope resides on several high-molecular-weight, membrane-associated proteins, and is likely to be composed of N-linked carbohydrate. These findings suggest that mAb 2F7 recognizes a novel epitope that is present on progenitor cells and postmitotic, differentiating neurons in the developing mammalian nervous system.
Promoter-Based Isolation and Fluorescence-Activated Sorting of Mitotic Neuronal Progenitor Cells from the Adult Mammalian Ependymal/Subependymal Zone
Authors: Wang Su , Roy Neeta S. , Benraiss Abdellatif , Goldman Steven A.
Published: April 2003

Neuronal precursor cells are widespread in the subependyma of the forebrain ventricular lining, and may provide a cellular substrate for brain repair. We have previously identified and isolated them from fetal brain, by sorting forebrain cells transfected with plasmid DNA encoding the gene for green fluorescent protein (hGFP), driven by the early neuronal promoter for Tα1 tubulin (P/Tα1). Fetal neuronal precursors were thereby identified and harvested with both a high degree of enrichment, and a virtual abolition of glial contaminants. We have now extended this approach to include the isolation and purification of neuronal progenitors from the adult brain. Dissociates of the lateral ventricular wall, that included the combined ependymal/subependymal zone, were obtained from 3-month-old adult rats. These cells were cultured and transfected with P/Tα1:hGFP plasmid DNA. Two days later, the cells were redissociated, sorted on the basis of Tα1-driven GFP expression, and replated. The majority of these cells expressed the early neuronal proteins Hu and TuJ1/βIII-tubulin upon FACS; within the week thereafter, most matured as morphologically-evident neurons, that coexpressed βIII-tubulin and MAP-2. Fewer than 5% expressed astrocytic markers, compared to over half of the cells in matched samples that were either not sorted, or sorted after transfection with a plasmid bearing the nonfluorescent lacZ gene under the control of P/Tα1 tubulin. Thus, the use of a fluorescent transgene under the control of an early neuron-selective promoter permits the enrichment of neuronal progenitor cells from the adult rat brain, in a form that may allow their heterologous implantation.
Sonic Hedgehog-Mediated Ventralization Disrupts Formation of the Midbrain-Hindbrain Junction in the Chick Embryo
Authors: Zhang Xiang-Mei , Lin Eddie , Yang Xian-Jie
Published: April 2003

The secreted signaling molecule Sonic hedgehog (Shh) plays critical roles in pattern formation of the vertebrate central nervous system. During neurulation, Shh is produced by the ventral midline mesoderm as well as by the ventral neural tube, and its activity is required for the determination of ventral characteristics along the anterior-posterior neuraxis. The morphological boundary between midbrain and hindbrain, the isthmus, is an important tissue organizer that regulates the development of both the midbrain and the anterior hindbrain. In this study, we report that retrovirus-mediated misexpression of Shh in the early chick neural tube disrupts formation of the boundary between the midbrain and the hindbrain, and causes a fusion of the bilateral cerebellum primordia. Dorsally expressed Shh signals induce ectopic transcription of its receptor Ptc1 in the midbrain and the hindbrain. The expression of several genes (Noggin, Lmx1, BMP7) along the dorsal midline of the midbrain is abolished, and ventral or lateral markers (HNF3β, Ptc1, ELF1) are induced in the dorsal brain. Furthermore, the normally restricted expression of two genes (En1 and Pax2) in the mid/hindbrain junction region are expanded, reflecting the morphological defects. These results suggest that maintaining proper dorsal-ventral patterns of the neural tube is essential for normal development of the mid/hindbrain region.
Antisense Studies in PC12 Cells Suggest a Role for H218, a Sphingosine 1-Phosphate Receptor, in Growth-Factor-Induced Cell-Cell Interaction and Neurite Outgrowth
Authors: MacLennan A. John , Devlin Brenda K. , Marks Lianne , Gaskin Amanda A. , Neitzel Karen L. , Lee Nancy
Published: April 2003

Our previous studies of H218, a sphingosine 1-phosphate (S1P) receptor and a member of the G-protein-coupled receptor superfamily, suggest that it may participate in mammalian nervous system development. Thus, brain levels of H218 mRNA are higher during early neurogenesis than postnatally. In addition, embryonic H218 immunoreactivity is preferentially localized in young neuronal cell bodies during their early stages of differentiation and in axons during their extension. This report describes the morphological effects of reducing native H218 levels in PC12 cells. Western blot analyses demonstrated that PC12 cells stably transfected with an expression vector carrying an antisense-oriented H218 cDNA contain less H218 protein than vector-transfected control cells. When differentiated with growth factors, the antisense-H218 cells display more neurite production and form less cell-cell contacts than the control cells. Therefore, these data, along with our previous H218 expression studies and a recent, independent study of H218 overexpression, support the possibility that H218 contributes to developmental processes regulating neuronal interaction and axon growth. The data are also consistent with reports that H218 is a S1P receptor, that S1P is present in serum, like that used in our PC12 cell cultures, and that it causes PC12 cell neurite retraction. Finally, and in agreement with a S1P receptor role for H218, we find that the antisense-H218 cells display less S1P-induced neurite retraction than control cells.
PKA Phosphorylations on Tau: Developmental Studies in the Mouse
Authors: Andorfer Cathy A. , Davies Peter
Published: April 2003

PKA phosphorylations of tau may be an early event in the development of neurofibrillary pathology in Alzheimer’s disease. Serines 214 and 409 of tau are highly phosphorylated in PHF-tau, but are not phosphorylated to any significant extent in normal adult human brain; both of these sites are phosphorylated in human fetal tissue. To further study this phenomenon, a developmental characterization of these phosphorylation sites relative to PKA, cAMP-dependent response binding element (CREB) and phosphorylated CREB was performed using samples from mouse brain. Immunoblot analysis using antibodies specific for phospho-serine 214 (CP-3) and phospho-serine 409 (PG-5) revealed a marked decrease in phosphorylation occurring at each of these sites between postnatal day 11 (P11) and P20. Immunoblots with TG-5, a pan-tau antibody, revealed uniform expression of tau during postnatal development, as well as a switch in isoform composition that is evident between P7 and P11. This switch in isoform composition just precedes the change in the extent of phosphorylation at serines 214 and 409, and occurs at a time when PKA phosphorylation of CREB is increasing.
Biochemical Characterization of the Mitochondrial Permeability Transition in Isolated Forebrain Mitochondria
Authors: Kristal Bruce S. , Staats Paul N. , Shestopalov Alexander I.
Published: April 2003

Induction of the mitochondrial permeability transition (PT) has been proposed to contribute to neuronal cell death. Nearly all studies of the biochemistry of PT induction, however, have been conducted in isolated liver mitochondria. To better understand PT induction in brain mitochondria, we used Ficoll gradients to purify nonsynaptosomal mitochondria from the forebrains of male Fischer 344 rats. Incubation of these mitochondria with Ca2+ was associated with a loss of absorbance. Inorganic phosphate enhanced this loss of absorbance, and the PT inhibitor cyclosporin A reduced it, especially in conjunction with ADP. These findings suggest that Ca2+-mediated loss of absorbance resulted from PT induction. Na+, which enhances mitochondrial Ca2+ efflux, but stimulates mitochondrial free radical production, had no effect on PT induction. These data confirm the existence of tissue-specific differences in the nature of PT induction.
Effect of Acute Insulin-Induced Hypoglycemia on Fetal versus Adult Brain Fuel Utilization, Assessed by 13C MRS Isotopomer Analysis of [U-13C]Glucose Metabolites
Authors: Lapidot A. , Haber S.
Published: April 2003

Tight glycemic control during diabetic pregnancy has been shown to significantly reduce the occurrence of congenital malformations and other effects of maternal diabetes on the offspring. However, intensive insulin therapy often causes recurring acute maternal hypoglycemia, which has been found to be harmful to the developing fetus, although the mechanisms involved are not clear. The aim of our work was to study the effect of acute insulin-induced maternal hypoglycemia on glucose metabolism in the fetal brain. To this end, near-term pregnant New Zealand rabbits were rendered hypoglycemic, and [U-13C]glucose was infused into maternal circulation. The metabolic fate of the 13C-labeled glucose was then studied in fetal brain extracts by 13C NMR isotopomer analysis, together with conventional biochemical assays of glucose and lactate levels in both plasma and brain. For comparison [U-13C]glucose was also administered to insulin-induced hypoglycemic young adult rabbits. Our results showed that while plasma glucose levels were significantly reduced (∼70%) relative to controls, no changes in cerebral glucose levels could be detected. Lactate levels were found to be significantly decreased in hypoglycemic fetal plasma and brain. No differences in lactate levels between control and hypoglycemic young rabbit plasma and brain were observed. These differences were attributed to the utilization of lactate as an energy substrate in the fetal brain, but not in the adult brain. Higher relative 13C enrichments of most glucose metabolites, except lactate, in the hypoglycemic fetal and young rabbit brains, observed by 13C NMR, stem from reduced endogenous plasma glucose pools, thereby diluting the labeled glucose to a lower extent. The relative glucose (or glucose-derived lactate) flux via the pyruvate carboxylase and pyruvate dehydrogenase pathways (PC/PDH ratio) was not altered under hypoglycemic conditions in the fetal brain for both glutamine and glutamate, but significantly increased in the adult brain for both glutamine and glutamate. The presented data indicate the ability of the fetal brain to maintain energy metabolism during acute hypoglycemia, via lactate utilization. The increase in the adult PC/PDH ratio was suggested by us to stem from increased PC activity, in order to replenish TCA cycle intermediates.
Psychotherapeutic Approach in Acne Treatment
Authors: Panconesi E. , Hautmann G.
Published: April 2003

From a medical psychological point of view, acne vulgaris can be schematically divided into two clinical pictures: (1) the common adolescent eruption, more mind-influencing and thus somatopsychic; (2) the less frequent acne of adults (young adults for the most part), both as a continuation of adolescent acne and, more rarely, as a never before experienced cutaneous affection, and thus psychosomatic in a strict sense. We believe that the dermatologist can treat both of these clinical manifestations, even from a psychological aspect, from the very first visit with the patient using the first step in psychotherapy: counseling. The principal points of this approach are presented, with special attention to the differences to be considered in the two clinical pictures specified as well as to the opportuneness and timing of an eventual liaison consultation with psychologists/psychiatrists in realizing other therapeutic strategies.
Systemic Antibiotics for Acne
Authors: Meynadier J. , Alirezai M.
Published: April 2003

Antibiotic therapy for acne is very common. Antibiotics are frequently used in acne, either systemically or topically. Systemic antibiotics are indicated as treatment of moderate and quite severe acne or if acne is considered as very serious by the patient for psychological or social reasons. Results are very often excellent, but failure is possible; in this case using another treatment, especially isotretinoin, is necessary. A few antibiotics are useful: tetracyclines (tetracycline, doxycycline, minocycline, lymecycline), erythromycin, co-trimoxazole and trimethoprim. Their side effects are reviewed. During pregnancy the best antibiotic is erythromycin. For the nursing mother it is generally said that tetracyclines are contraindicated but the risks if they exist are certainly slight. The mechanism of action of systemic antibiotics for acne is not perfectly clear as it is not only antimicrobial: they diminish chemotaxis of polymorphonuclear leukocytes, modify the complement pathways and inhibit the polymorphonuclear leukocyte chemotactic factor and the lipase production in Propionibacterium acnes.
The Possible Role of Reactive Oxygen Species Generated by Neutrophils in Mediating Acne Inflammation
Authors: Akamatsu H. , Horio T.
Published: April 2003

The purpose of this study was to investigate the possible role of reactive oxygen species (ROS) generated by neutrophils in mediating acne inflammation. Antibiotics used for the treatment of acne significantly inhibited ROS generated by neutrophils, when compared to other antibiotics. Metronidazole, which is effective in the treatment of acne, markedly inhibited ROS generated by neutrophils. The drug is known to have no significant effect on the growth of Propionibacterium acnes. The proportion of linoleic acid is markedly decreased in acne comedones. Linoleic acid significantly suppressed ROS generated by neutrophils. The ability of neutrophils to produce ROS was significantly increased in patients with acne inflammation. These results seem to reveal the involvement of ROS generated by neutrophils in the disruption of the integrity of the follicular epithelium, which is responsible for inflammatory processes of acne.
Epiluminescence Microscopy versus Clinical Evaluation of Pigmented Skin Lesions: Effects of Operator’s Training on Reproducibility and Accuracy
Authors: Stanganelli I. , Bucchi L. , Dermatology and Venereology Society of the Canton of Ticino L.
Published: April 2003

Background: An acceptable level of reliability is a prerequisite for the introduction of epiluminescence microscopy (ELM) into the diagnosis of pigmented skin lesions. Objective: To assess the effects of a training program on the reproducibility and accuracy of ELM as compared to clinical evaluation. Methods: Before and after the program, 48 clinical images and their ELM counterparts were independently evaluated by seven participants. Reproducibility was measured by the κ index, accuracy by the rate of exact diagnoses (RED) assuming histology as a reference. Results: We observed (i) no effect of training on clinical reproducibility, (II) an improved reproducibility of ELM diagnoses of nonmelanocytic lesions (NML) and melanomas but not of melanocytic nevi (MN), (iii) a greater increase in the clinical RED of NML and melanomas compared with MN and (iv) a similar though more pronounced increase in the RED on ELM. Conclusions: The effects of training were greater for ELM as compared to clinical diagnosis, and for NML and melanomas as compared to MN.
Lectitis purulenta et granulomatosa
Authors: Eichmann A. , Baran R.
Published: April 2003

A granulomatous purulent nail bed inflammation of the great toenails in a 69-year-old female patient is described. The successful treatment consisted of intra- and perilesional corticosteroide injections in addition to systemic antibiotic treatment.
Photoallergic Contact Dermatitis due to Combined UVB (4-Methylbenzylidene Camphor/Octyl Methoxycinnamate) and UVA (Benzophenone-3/Butyl Methoxydibenzoylmethane) Absorber Sensitization
Authors: Schmidt T. , Ring J. , Abeck D.
Published: April 2003

In a 71-year-old male Caucasian patient with persistent eczema on light-exposed skin, photocontact allergy was demonstrated to the UV filter substances 4-methylbenzylidene camphor (UVB), octyl methoxycinnamate (UVB), benzophenone-3 (UVA) and butyl methoxydibenzoylmethane (UVA) present in sunscreen products used by the patient over several years. A significantly reduced UVB sensitivity of 25 mJ/cm2 in this patient (normal minimal erythema dose in our laboratory = 70–130 mJ/cm2) was considered an early indication of a persistent light reaction. Topical anti-inflammatory treatment over 2 weeks together with consequent application of a sunscreen containing Mexoryl® SX/titanium dioxide led to complete remission.Taking into account the widespread use of the above UV filter substances not only in sun protection products, but also in cosmetics such as antiaging lotions and day care products, the possible risk of allergy to these chemicals has to be taken seriously. The substitution of known photocontact sensitizers in UV filters by photostable compounds and detailed product information are the basis of preventive strategies.
Acrocyanosis Induced by Interferon α2a
Authors: Campo-Voegeli A. , Estrach T. , Marti R.M. , Corominas N. , Tuset M. , Mascaró J.M.
Published: April 2003

A 56-year-old woman with mycosis fungoides developed acrocyanosis each time treatment with interferon α2a was started. Acrocyanosis disappeared after discontinuing therapy. Immunological study performed while acrocyanosis was present showed elevated antinuclear antibody (ANA) titers and circulating immune-complex levels. Long-term interferon treatment has been related to autoimmune side effects. Raynaud’s phenomenon has been observed in patients undergoing interferon treatment associated with elevated ANA titers, to cryoglobulinemia or to arterial occlusion. Acrocyanosis has never before been described as side effect in patients undergoing this treatment. We believe that our patient’s acrocyanosis must be considered a side effect of interferon.
Management of Severe Scleroderma with Long-Term Extracorporeal Photopheresis
Authors: Krasagakis K. , Dippel E. , Ramaker J. , Owsianowski M. , Orfanos C.E.
Published: April 2003

Background: The management of systemic sclerosis remains unsatisfactory. Thus far, the action of extracorporeal photopheresis (ECP) in severe systemic scleroderma has been evaluated in short-term studies, and only limited experience has been obtained with long-term application. Objective: The aim of the present study was to evaluate prospectively the long-term effect of ECP in a group of 16 patients suffering from severe scleroderma, showing visceral involvement and progressive clinical course. Methods: Fourteen patients with systemic scleroderma involving several organs, 1 with CREST syndrome and another with scleroderma-myositis overlap syndrome were treated with ECP over a period of 6–45 months. In 3 cases, γ-IFN was additionally administered. Skin and visceral involvement were assessed by evaluating a series of clinical criteria and results from laboratory, imaging and functional tests. Results: Overall, clear improvement was encountered in 6 patients, mixed response in 2, stable disease in 3 and continuing progressive course in 5 patients. Four out of 6 patients with improvement were treated with ECP early after onset of scleroderma (≤2 years), whereas all patients with a progressive course under ECP had had scleroderma for longer than 2 years. Immunosuppressive drugs previously administered could be reduced or fully withdrawn under ECP treatment in 5 patients, but additional oral medication was introduced in 4 patients due to disease progression. Addition of γ-IFN to ECP did not reveal further benefit. No side-effects were recorded under ECP treatment. Conclusions: Based on this observation, we believe that long-term ECP represents an effective treatment modality in severe scleroderma particularly when started early, with stabilization of the disease course and partial remission of the cutaneous findings, whereas visceral involvement, if present, may rarely improve.
Contact Dermatitis with Systemic Symptoms from Agave americana
Authors: Brenner S. , Landau M. , Goldberg I.
Published: April 2003

Background: Twelve cases of contact dermatitis provoked by Agave americana are described, 10 with systemic signs and symptoms and 8 with abnormal laboratory results. Results: Patient history revealed a background of intentional exposure among soldiers seeking sick leave. Treatment with oral antihistamines and topical saline compresses resulted in subsidence of the systemic symptoms within 24 h of hospitalization and regression of cutaneous manifestations in 7–10 days. Conclusion: The importance that dermatologists be alert to the possibility of self-inflicted contact dermatitis induced by exposure to plants is stressed, especially to A. americana. Systemic signs are not rare accompanying findings with this plant.
Atrophic Dermatofibrosarcoma protuberans: A Case Report and Review of the Literature
Authors: Fujimoto M. , Kikuchi K. , Okochi H. , Furue M.
Published: April 2003

Dermatofibrosarcoma protuberans is not a difficult tumor to recognize because of its characteristic clinical appearance, although some unusual variants have been reported. We describe the atrophic variant of dermatofibrosarcoma protuberans in a 21-year-old female. The lesion was a smooth-surfaced, oval depression on the left subclavicular area, with a violaceous plaque at the center. The suspected clinical diagnosis did not include fibrous tumors, although histological examination showed the typical picture of dermatofibrosarcoma protuberans. Positive CD34 staining was also helpful in the diagnosis. We review 14 cases of the atrophic variant of dermatofibrosarcoma protuberans in the literature. Dermatologists should be aware of this uncommon but characteristic appearance of atrophic dermatofibrosarcoma protuberans.
Role of Viral Agents in the Pathogenesis of Kaposi’s Sarcoma
Authors: Simonart T. , Noel J.C. , van Vooren J.P. , Parent D.
Published: April 2003

Several viruses have been detected, at various frequencies, in Kaposi’s sarcoma (KS) tissues. The detection of human herpesvirus 8 (HHV-8) in all the epidemiological and histological forms of KS makes it the most attractive candidate causative agent to date. In this report, we discuss the possible explanations for the detection of genomic sequences of various viral agents in KS and the putative role of those viruses in the pathogenesis of the disease.
Angiokeratoma corporis diffusum Associated with Galactosialidosis
Authors: Kawachi Y. , Matsu-ura K. , Sakuraba H. , Otsuka F.
Published: April 2003

We describe a 34-year-old Japanese man with generalized angiokeratomas and various neurological symptoms since childhood. A number of reddish papules were scattered over his entire body and were especially numerous on his elbows, knees, penis and scrotum. An electron-microscopic study revealed a number of vacuoles in the cytoplasm of the vascular endothelial cells. This finding suggests that the angiokeratomas resulted from an injury of the endothelial cells due to the storage of metabolic material. A laboratory examination demonstrated a deficiency of both the β-galactosidase and neuramidase activity in his leukocytes and fibroblasts. A restriction site analysis of PCR-amplified genomic DNA revealed that the patient had an mRNA splicing junction mutation at the 5′ donor splice site of the exon 7/intron 7 junction in the protective protein gene.
Graft-versus-Host-Like Mucocutaneous Eruptions with Serological Features of Paraneoplastic Pemphigus and Systemic Lupus erythematosus in a Patient with Non-Hodgkin’s Lymphoma
Authors: Mahler V. , Antoni C. , Anhalt G.J. , Koch H.-J. , Peters K.-P. , Manger B. , Kalden J.R. , Hornstein O.P.
Published: April 2003

A 63-year-old male patient spontaneously developed severe erosive orogenital mucositis, palmoplantar and gluteal inflammatory lesions resistant to therapy. The skin lesions clinically and histologically resembled lichen-planus-like graft-versus-host disease. Investigation for an underlying autoimmune or malignant disorder revealed a centrocytic-centroblastic low-grade non-Hodgkin’s lymphoma (according to the Kiel classification) in the bone marrow, mesenterial and iliacal lymphoma. Serological titers were intermittently positive for ANA, anti-Sm/U1RNP, anti-Ro and anti-dsDNA. Immunoprecipitation of lysates from radiolabeled human keratinocytes with the patient’s serum revealed circulating antibodies against 210-kD (desmoplakin II), 190- and 170-kD antigens but none against the 230-kD antigen or 250-kD desmoplakin I. Under cytostatic chemotherapy the lymphomas showed complete and long-lasting remission, whereas the mucocutaneous lesions persisted. Six years after diagnosis, the mucocutaneous lesions are sufficiently controlled by immunosuppressive therapy. In the presented case, several features of lymphoma-associated dysimmunoreactivity are assumed that bring about the intrinsic production of various autoantibodies typical of paraneoplastic pemphigus and systemic lupus erythematosus.
Semiological Value of ABCDE Criteria in the Diagnosis of Cutaneous Pigmented Tumors
Authors: Thomas L. , Tranchand P. , Berard F. , Secchi T. , Colin C. , Moulin G.
Published: April 2003

Objective: The aim of this study was to evaluate the semiological value of the so-called ABCDE criteria in the differential diagnosis of pigmented tumors. Aside from the classical ABCD criteria, an E criterion for ‘enlargement’ is studied. Material and Methods: Records from melanoma patients were obtained from a melanoma database prospectively including patients treated for melanoma in our department since 1992; 460 files were found informative for this study. A prospective control group was established including 680 cases of benign pigmented tumors. All cases included in the study were histopathologically controlled in our dermatopathology unit. Records of ABCDE, i.e. corresponding to asymmetry, irregular borders, irregular coloration, diameter ≥6 mm and enlargement, were codified as present or absent in every case. Data were statistically compared for every individual criterion with the χ2 test and for the number of criteria present in melanoma versus other pigmented tumors with Student’s t test. Results: Significant differences were observed for all individual criteria (p <0.001) between melanomas and common nevi. Significant differences were also observed for B, C and E criteria between melanomas and atypical nevi. The sensitivity of the individual criteria for the diagnosis of melanoma was 57, 57, 65, 90 and 84% for ABCDE, respectively. The specificity of the individual criteria for the diagnosis of melanoma versus other pigmented tumors was 72, 71, 59, 63 and 90% for ABCDE, respectively. The number of criteria present was significatively different between common nevi (1.24 ± 1.26) and melanomas (3.53 ± 1.53; p <0.001) and between common nevi and atypical nevi (3.62 ± 0.83, p <0.001), but no significant difference was found between melanomas and atypical nevi. Sensitivity and specificity of diagnosis of melanoma are 89.3 and 65.3% if 2 criteria are present. Sensitivity and specificity of diagnosis of melanoma are 65.5 and 81% if 3 criteria are present. Conclusion: The so-called ABCD criteria have a good semiological value in the differential diagnosis of pigmented tumors. Addition of an E criterion for enlargement optimizes sensitivity and specificity of diagnosis.
Comparison of 8-MOP Aqueous Bath and 8-MOP Ethanolic Lotion (Meladinine®) in Local PUVA Therapy
Authors: Shephard S.E. , Schregenberger N. , Dummer R. , Panizzon R.G.
Published: April 2003

Background and Objective: Local PUVA (psoralen plus UVA light) is an effective outpatient treatment for patients with palmoplantar eczema or psoriasis. In this study, the efficacy, applicability and patient acceptance of two local forms of 8-methoxypsoralen (8-MOP) PUVA therapy were compared. Methods: The study design was a left-right comparison (n = 37): the left hand or foot was treated with (aqueous) 8-MOP bath PUVA whereas the right received (ethanolic) 8-MOP lotion PUVA. After 1 month, the more successful treatment was continued on both sides until lesions cleared. Results: Both therapies were effective and both useful for particular clinical applications: patients with erosive lesions and rhagades appreciated the gentleness of bath PUVA. Those with pustules or hyperkeratotic lesions appreciated the greater effectiveness of 8-MOP lotion PUVA. The total UVA dose and number of sessions to clearance were smaller with 8-MOP lotion. There was no difference in the length of the relapse-free period. Therapy nonresponders usually became apparent within the first 12 sessions. Conclusions: The difference between bath PUVA and lotion PUVA can be described as ‘gentle’ versus ‘strong’ therapy. The better therapy depends on clinical indication.
Expression of Stem Cell Factor in the Lesional Skin of Systemic Sclerosis
Authors: Yamamoto T. , Katayama I. , Nishioka K.
Published: April 2003

Background and Objective: Mast cells are thought to play an important role in the pathogenesis of systemic sclerosis (SSc), although their significance is still unknown. As mast cells are increased in number in the lesional skin of the early stage of scleroderma, we addressed the question whether expression of stem cell factor (SCF), a mast cell growth factor, is upregulated in the lesional skin. Methods: Immunohistochemical analysis of SCF was performed in paraffin-embedded skin sections from the lesions of 18 patients with SSc (13 in the edematous and 5 in the sclerotic phase) and from normal skin of 5 subjects. SCF messenger RNA expression was also examined on cultured fibroblasts derived from SSc by using reverse-transcriptase polymerase chain reaction. Results: Immunostaining showed focal expression for SCF in fibroblast-like spindle-shaped cells, mast cells, keratinocytes and endothelial cells. SCF-positive spindle-shaped cells were significantly increased in the reticular dermis in the early edematous stage of SSc (33.7 ± 13.0/mm2) as compared with normal skin (18.3 ± 4.2/mm2; p <0.05); however, there was no significant difference between the sclerotic phase (18.9 ± 6.9/mm2) and normal skin. mRNA expression of SCF was detected both in cultured scleroderma-derived and normal skin-derived fibroblasts. Conclusion: These results may suggest that SCF plays a role in the fibrotic process in early-stage SSc.
Abscess-Forming Neutrophilic Dermatosis: Report of Three Cases Associated with Hemopathies
Authors: Horiguchi Y. , Lee S.-G. , Matsumoto I. , Arima N. , Fujii H. , Ohnuma Y. , Imamura S.
Published: April 2003

Background: The development of different types of neutrophilic dermatosis is reported to occur in the course of malignant hemopathies. These concern mainly Sweet’s syndrome, pyoderma gangrenosum, erythema elevatum et diutinum and neutrophilic eccrine hidradenitis. Observations: We have recently encountered the cases of 3 patients who presented all with multiple acneiform papules and dome-shaped aseptic abscesses leaving scars. Pus was sterile in all except case 3 in which slight Staphylococcus aureus growth was shown. However, in this patient, only steroids were effective demonstrating that this bacterium was not responsible for the disease. Histopathology disclosed a dense dermal polymorphonuclear neutrophil infiltrate and some mononuclear cells. Two of these patients had myelodysplastic syndromes while one had IgA myeloma. Conclusion: Abscess-forming neutrophilic dermatosis seems to be another type of neutrophilic dermatosis associated with hematological malignancies.
Reproducibility of the Finn Chamber® Nickel Patch Test in Two Different Phases of the Ovulatory Menstrual Cycle
Authors: Aktan Şebnem , Aktan Erdal , Inanir Işıl , Kaleli Babür , Şanli Berna
Published: April 2003

Background: Studies on nickel patch test reactivity and reproducibility of positive tests at different points of the menstrual cycle are heterogeneous. Objective: To investigate if non-reproducibilities of positive nickel sulphate patch tests in the two different phases of ovulatory menstrual cycles with the endocrine evidence of luteal phase adequacy are statistically different. Methods: 15 women (group 1) with positive Finn chamber® nickel patch test results in the follicular phase of the ovulatory cycle and 13 women (group 2) with positive Finn chamber nickel patch test results in the luteal phase of the ovulatory cycle were tested again in the counter-phases of their ovulatory cycle, with a scheduled interval of 6 weeks following the first tests. Reproducibilities of the tests in the two groups were evaluated statistically. Results: 3 of the positive test results in group 1 (20%) and 2 of the positive test results in group 2 (15.4%) were non-reproducible. The difference was not statistically significant. Conclusion: The reproducibility of positive Finn chamber nickel patch tests does not seem to be affected by the changes in the follicular and luteal phases of the ovulatory cycle.
Photodynamic Therapy of Superficial Basal Cell Carcinomas Using Topical 5-Aminolevulinic Acid in a Nanocolloid Lotion
Authors: Hürlimann A.F. , Hänggi G. , Panizzon R.G.
Published: April 2003

Background: Photodynamic therapy (PDT) of superficial basal cell carcinomas using endogenous protoporphyrin IX generated by topically applied 5-aminolevulinic acid (5-ALA) is an innovative and clinically encouraging approach. Objective: This paper reports on the first results of an ongoing clinical study on photodynamic therapy of 55 basal cell carcinomas in 19 patients. Methods: Because of the chemical instability of 5-ALA, a novel nanocolloid lotion was developed. This formulation was applied to the lesions under occlusive dressing 6 h before irradiation with visible light from an unfiltered halogen lamp. Light-induced fluorescence was used to ascertain the superficial extension of the tumors. The response to the therapy was assessed by visual inspection and in 13 patients also by biopsies. Results: After a single treatment, 47 (85%) basal cell carcinomas showed a complete response at a follow-up time of at least 6 months. For the remaining 8 (15%) lesions, a partial response was observed, indicated by a marked reduction of the tumor size. The treatment modality without local anesthetics was well tolerated by all patients, with only slight discomfort during light irradiation. Conclusion: Our results indicate that 5-ALA-PDT with our novel formulation, a nanocolloid lotion, is a highly effective and convenient therapy for the treatment of superficial basal cell carcionomas. Its use in the treatment of nodular tumors needs further investigations.
Treatment of Acyclovir-Resistant Herpetic Ulceration with Topical Foscarnet and Antiviral Sensitivity Analysis
Authors: Pechère M. , Wunderli W. , Trellu-Toutous L. , Harms M. , Saura J.-H. , Krischer J.
Published: April 2003

Background: Herpes simplex virus (HSV) can produce persistent mucocutaneous disease in patients with the acquired immunodeficiency syndrome (AIDS). In this case report, we evaluate the efficacy, safety and viral resistance after topical foscarnet in severe genital ulceration due to acyclovir-resistant HSV-2. Case Report: A 45-year-old African woman was known for an HIV infection with severe immunosuppression (CD4 <100/mm3). She had received a long-term prophylaxis with acyclovir (400 mg b.i.d.) for a recurrent genital herpes. Few weeks after stopping this prophylaxis, she developed large genital ulcerations progressing despite valacyclovir treatment (1,000 mg t.i.d.). Cultures were positive for HSV-2, resistance to acyclovir was shown by the plaque reduction assay and topical foscarnet was tried. Treatment consisted of a 20-min application of topical foscarnet 2.4% twice a day. Dramatic improvement was observed with rapid antalgia, and cicatrization of the genital ulcerations was observed after 50 days. HSV could not be detected on the mucosal surface. Initially, HSV-2 was resistant to acyclovir but sensitive to foscarnet. After 1 month of topical treatment, HSV-2 became sensitive to acyclovir and was still sensitive to foscarnet. Finally, after 6 weeks of treatment, no virus could be detected by culture. Conclusion: Topical foscarnet (2.4%) is a convenient treatment for chronic genital herpes. Resistance to acyclovir disappears few weeks after stopping this drug and sensitivity to foscarnet persists during the 50 days of treatment.
Delayed Telogen Replacement in a Boy’s Scalp
Authors: Guarrera M. , Cipriani C. , Rebora A.
Published: April 2003

Background: In case the shedding telogen hair is not replaced in time by a terminal anagen hair, an empty space results. Objective: To verify whether the phenomenon is present in prepubertal subjects. Methods: From July 1996 to May 1997, an 8-year-old boy was submitted monthly to the phototrichogram technique. Sixty hairs were monitored throughout the study. Results: 52% of all studied hairs were terminal anagen hairs throughout the study and additionally 22% were in a regular hair cycle. Vellus hairs and empty spaces were observed in 18 and 8% of follicles, respectively. In 2% of hairs, vellus hairs and empty spaces were associated. Conclusions: Vellus hairs and empty spaces are present even in children. Without gonadal androgens and expression or induction of 5α-reductase in the prepubertal scalp, they are unlikely to herald androgenetic alopecia (AGA) but could reflect a physiological phenomenon of ‘true resting’ of a small proportion of scalp hair. Androgens may increase the phenomenon which may account in part for AGA development.
Peeling Skin Syndrome with Hair Changes
Authors: Mevorah B. , Orion E. , de Viragh P. , Bergman R. , Gat A. , Legume C. , van Neste D.J.J. , Brenner S.
Published: April 2003

A 13-year-old boy with typical peeling skin syndrome (PSS) is described. The clinical picture corresponded to the inflammatory variant of PSS (type B). In addition, the patient had gross and microscopic hair anomalies such as trichorrhexis invaginata-like changes, irregular hair shaft torsions and moniliform hair shaft diameter reductions. The observed dysmorphic hair changes are discussed and interpreted as being an integral component of the dermatosis in this case. To the best of our knowledge, such hair anomalies have not yet been described in PSS.
Basal Cell Carcinoma within Vulvar Paget’s Disease
Authors: Ishizawa T. , Mitsuhashi Y. , Sugiki H. , Hashimoto H. , Kondo S.
Published: April 2003

An 85-year-old Japanese woman had noticed erythema on her vulvar region 3 years before. The erythema gradually increased in size and followed erosion and ulceration with pigmentation on the edge of the erythema. A skin biopsy from the pigmented area showed large round cells with ample cytoplasm, which formed nests or glandular structures. In the dermis there was mass formation of basophilic cells and peripheral cells in a palisade arrangement. The tumor cells in the epidermis showed positive immunoreactivity for carcinoembryonic antigen; on the other hand, the dermal tumor was negative. We diagnosed that the tumor in the epidermis was vulvar Paget’s disease, and the dermal tumor was a solid type of basal cell carcinoma. We speculate that the vulvar Paget’s disease preceded and then the basal cell carcinoma developed in the area of Paget’s disease. This is the first report in which basal cell carcinoma in the area of Paget’s disease was documented.