Pemphigus and pemphigoid-like effects of nifedipine on in vitro cultured normal human skin explants.

BACKGROUND: A variety of drugs have been implicated in the onset and exacerbation of pemphigus and bullous pemphigoid. The demonstration of biochemical acantholysis in skin explants to various drugs in the absence of autoantibodies, in which the tested drugs evoke a biochemical reaction that leads to desmosomal function loss, may be a valuable adjunct to patient management by confirming the suspicion of drug-related pemphigus or bullous pemphigoid. OBJECTIVE: To determine whether a skin explant model might serve as a possible in vitro correlate of drug-induced pemphigus and pemphigoid-like effects related to the calcium channel blocker nifedipine. METHODS: Normal human breast skin obtained from nonpemphigus and nonpemphigoid patients undergoing mastectomy was cultured with nifedipine at final concentrations of 2, 4, and 8 mM. The drug effect on skin explants evidenced by morphologic changes was evaluated by microscopy by three observers. RESULTS: Five out of seven explants cultured with nifedipine at concentrations ranging from 2 to 8 mM exhibited obvious morphologic changes of two types: intraepithelial (or pemphigus-type) splittings and subepithelial (or pemphigoid-type) splittings. Two explants showed no acantholysis and no subepithelial splittings. Control cultures without polyethylene glycol 200 (PEG) showed no changes. Skin control samples cultured in medium supplemented with 10% PEG displayed vacuolar degeneration throughout the entire epidermis, but no sign of cell-cell dyshesion or dermo-epidermal detachment. CONCLUSIONS: A type of skin susceptibility to nifedipine may be genetically determined, with some nifedipine-treated patients developing an acantholytic reaction and others a subepidermal bullous eruption.

Something fishy in the rat brain: molecular genetics of the hypothalamo-neurohypophysial system.

The brain peptides vasopressin and oxytocin play crucial roles in the regulation of salt and water balance. The genes encoding these neurohormones are regulated by cell-specific and physiological cues, but the molecular mechanisms remain obscure. New strategies, involving the introduction of rat transgenes into rats, are being used to address these issues, but the complexity of the rat genome has hampered progress. By contrast, the pufferfish, Fugu rubripes, has a "junk-free" genome. The oxytocin homologue from Fugu, isotocin, has been introduced into rats and is expressed in oxytocin neurons, where it is upregulated by physiological perturbations that upregulate the oxytocin gene. The Fugu and rat lineages separated 400 million years ago, yet the mechanisms that regulate the isotocin and oxytocin genes have been conserved. Fugu genome analysis and transgenesis in the physiologically tractable rat host are a powerful combination that will enable the identification of fundamental components of the neural systems that control homeostasis.

Estenose de reto após trauma de pelve: relato de um caso / Rectal stenosis after pelvic trauma: a case report

Os autores apresentam um relato de caso de estenose tardia de reto, conseqüente a trauma de bacia. A paciente H. F. S., 52 anos, foi atendida no pronto-socorro, após acidente de trânsito, colisäo entre veículos. Apresentava disjunçäo sacro-ilíaca esquesda, fratura bilateral de fêmur e perna esqueda, TCE leve, contusöes e escoriaçöes generalizadas. O tratamento imediato foi traçäo de membros inferiores e com fixador externo na perna. Ficou internada por 65 dias, recebendo alta hospitalar com consolidaçäo óssea quase completa das fraturas. Durante o internamento teve um quadro de diarréia e obstipaçäo. Após sete dias da alta evoluiu com quadro de suboclusäo intestinal, tratada clinicamente, apresentando diarréia e constipaçäo. A história pregressa ao trauma revelava hábito intestinal normal. Foi encaminhada ao serviço de cirurgia apresentando distensäo abdominal, dor pélvica, ao toque evidenciava uma estenose de 90 por cento da luz retal a 6 cm da linha anorretal. A retoscopia demonstrou sinais de retite, hiperemia de mucosa e microulceraçöes ao nível da estenose. A biópsia diagnosticou proctite crônica inespecífica. Foram descartadas patologias como proctite estenosante por clamídia e sífilis. A T.A.C. foi normal e o enema opaco demonstrou estenose circular curta no reto. O diagnóstico final foi de estenose de reto causada por trauma de bacia e disjunçäo sacro-ilíaca. O tratamento inicial foi de dilataçäo por retossigmoidoscópio e digital, o qual näo foi satisfatório. O tratamento definitivo foi a retossigmoidectomia com anastomose colorretal com grampeador intraluminar. A paciente evoluiu satisfatoriamente estando atualmente normal. Concluímos que o trauma pélvico de modo geral pode levar a lesäo do reto por este ser fixo a estruturas vizinhas e a evoluçäo para estenose se näo tratada precocemente. O tratamento por dilataçäo digital é um modo alternativo porém näo eficaz e o tratamento definitivo é a retossigmoidectomia

Supplemental tests in the evaluation of occupational hand dermatitis in soldiers.

BACKGROUND: Hand dermatitis in soldiers is a considerable problem. The purpose of the study was to evaluate appropriate screening tests to improve the diagnosis of hand dermatitis in soldiers. MATERIALS AND METHODS: A group of 111 soldiers with occupational dermatitis from contact with fuels and oils underwent "tailored patch tests" with allergens relevant to their field of work and their environment. The control group consisted of 24 soldiers with various jobs similar to those of civilian life, who had not been exposed to oils and fuels. Seventy-three civilian patients, attending the clinic for patch testing, were also included. Twenty soldiers, who had a history of intensive contact with oil and fuels, but no contact dermatitis, and who were admitted because of various skin diseases (fungal infections, acne, etc.) also underwent the supplemental testing and served as an additional control group. RESULTS: Of the soldiers, 31 (29%) showed one or more positive skin tests of the oil series and 30 patients of this group one or more positive reactions to the standard patch tests trays. No patient of the control groups had a positive test to the oil series. CONCLUSIONS: Our results show the value of the supplementary tests as a first-step screening test for detection of oil allergy in soldiers and automobile-mechanics or in workers handling other gasoline- or diesel-powered engineering equipment. The test method appears to be practical, easy to perform, reliable and giving clear and accurate results, with a negligible rate of false positive reactions.

A case of diet-related pemphigus.

An experimental investigation has lately shown that certain allyl compounds of garlic are able to provoke acantholysis in normal human skin cultured in vitro. The acantholytic effect has been more prominent in the samples from DR4+ donor. We here report a case of superficial pemphigus which appeared spontaneously in a DR4,14+, 49-year-old man and which ran a course that proved to be affected by dietary factors, in particular by the consumption of garlic. In the absence of a conventional treatment and on a garlic-free diet only, the disease ceased for several months. Soon after an unintentional dietary test with a strongly and presumable garlic-spiced fish meal, the pemphigus recurred. Nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing or perpetuating pemphigus in genetically predisposed individuals.

Organization of host-inducible transcripts on the symbiotic plasmid of Rhizobium sp. NGR234.

In a systematic approach to identify genes involved in the early steps of the legume-Rhizobium symbiosis, we studied transcription patterns of symbiotic plasmid-borne loci. A competitive hybridization procedure was used to identify DNA restriction fragments carrying genes whose expression is enhanced by plant root exudates or by purified flavonoids. Fragments containing induced genes were then located on the physical map of the 500 kb pNGR234a. New inducible loci as well as previously described genes were identified and their time course of induction determined. After initial induction, transcription of loci such as nodABC and the host-specificity genes nodSU decreased to undetectable levels 24 h after incubation with purified flavonoids. In contrast, expression of other loci is detectable only after several hours of induction. Surprisingly, many genes remained transcribed in the nodD1- mutant suggesting the presence of other flavonoid-dependent activators in NGR234. The hsnl region, which is involved in host specificity, was shown to carry several inducible but independently regulated transcripts. Sequencing analysis revealed several open reading frames whose products, based on sequence similarities, may be involved in L-fucose metabolism and its adjunction to the Nod factors.

Pemphigus and dietary factors. In vitro acantholysis by allyl compounds of the genus Allium.

BACKGROUND: Today it is generally accepted that every drug that possesses an active thiol group in its molecule is capable of inducing pemphigus in vivo and provoking acantholysis in vitro. We therefore suggested that plants, in particular those belonging to the Allium group, that contain several active compounds with stable disulfide and thiol groups in their molecule may cause the same. OBJECTIVE: To verify this hypothesis by investigating the in vitro acantholytic effect of three compounds of garlic. METHODS: Skin samples from donors were cultured in the presence of three compounds of garlic (i.e. allylmercaptan, allylmethylsulfide and allylsulfide) for 3 days. The skin samples were then processed for microscopic control for acantholysis. RESULTS: Results indicate that, indeed, the three garlic compounds tested are capable of inducing acantholysis in vitro. Focal and diffuse acantholysis was observed in the specimens from 4 out of 7 donors cultured in the presence of 6 and 9 mM of each of the allyl compounds for 3 days. Interestingly, tissues from a DR4+ donor proved to be more acantholysis prone than others, showing large blistering due to diffuse acantholysis, thus indicating that individual susceptibility plays a crucial role also in vitro. CONCLUSION: Garlic compounds with stable disulfide and thiol groups in their molecule are capable of inducing acantholysis in vitro. These findings lend further support to the theory that 'harmless' nutritional factors are capable of inducing acantholysis in vitro and possibly also in vivo. In view of these findings, it is suggested that nutritional factors should be added to the ever-growing list of exogenous factors capable of inducing pemphigus.

Contact dermatitis in Israeli soldiers.

This report consists of an evaluation of 41 soldiers from the infantry, armored, and artillery division, who developed hand dermatitis from their contact with oils and fuel. A special "tailored" supplementary tray with five reagents relevant to their field of work and environment was performed. The reagents that were used were gun oil, hydraulic oil, automotive lubricant (oil) 20/50, white spirit, and car petrol (gasoline). Seven of the 41 patients (17%) showed one or more positive tests to the supplementary tray. The fact that none of the control group of 64 patients not exposed to these substances showed a positive result to the supplementary tray indicates that false positive results are, at least, not probable. It is suggested that soldiers with occupational hand dermatitis should be tested with supplemental aimed trays that are relevant to their work and environment, in addition to the standard trays.

Subtraction hybridisation and shot-gun sequencing: a new approach to identify symbiotic loci.

Traditionally, new loci involved in the Rhizobium-legume symbiosis have been identified by transposon mutagenesis and/or complementation. Wide dispersal of the symbiotic loci in Rhizobium species NGR234, as well as the large number of potential host-plants to be screened, greatly reduces the efficiency of these techniques. As an alternate strategy designed to identify new NGR234 genes involved in the early stages of the symbiosis, we combined data from competitive RNA hybridisation, subtractive DNA hybridisation and shot-gun sequencing. On the assumption that the expression of most nodulation genes is triggered by compounds released by the host-plant, we identified, in the ordered cosmid library of the large symbiotic plasmid pNGR234a, restriction fragments that carry transcripts induced by flavonoids. To target genes not present in the closely related strain R. fredii USDA257, we selected fragments that also carried sequences purified by subtractive DNA hybridisation. Shot-gun sequencing of this subset of fragments lead to the identification of sequences with strong homology to diverse prokaryotic genes/proteins. Amongst these, a symbiotically active ORF from pNGR234a, is highly homologous to the leucine responsive regulatory protein of Escherichia coli (Lrp), is induced by flavonoids, and is not present in USDA257.

A novel calmodulin-like gene from the nematode Caenorhabditis elegans.

A novel gene from the nematode Caenorhabditis elegans was isolated by hybridization with a human calmodulin complementary DNA probe. This gene, cal-1, is present at one copy per haploid genome. In-situ hybridization of the cloned gene to metaphase chromosomes allowed us to assign it to the nematode linkage group IV. The polypeptide predicted from the sequence of this gene displays structural features of both calmodulin and troponin C.

Fungitoxic effects of nonprotein imino acids on growth of saprophytic fungi isolated from the leaf surface of Calliandra haematocephala.

Four saprophytic and pathogenic fungi were isolated from the leaf surface of Calliandra haematocephala, a tropical legume known to contain large amounts of rare nonprotein imino acids in its leaves and seeds. The fungi Aspergillus niger, Aspergillus sp., Curvularia sp., and Penicillium sp. were cultured in the laboratory and tested for susceptibility to leaf extracts of the host plant and to proline, pipecolic acid, cis-5-hydroxypipecolic acid, and 2,4-trans-4,5-cis-4,5-dihydroxypipecolic acid. Fungal spore germination and germ tube growth were measured. Aspergillus sp. was inhibited by plant extracts and by pipecolic acid and cis-5-hydroxypipecolic acid. Curvularia sp. growth was stimulated by plant extracts and by pipecolic acid. The other two fungi were unaffected by any of the treatments. The data indicate that imino acids may play a role in the specific resistance of Calliandra spp. to Aspergillus sp.