Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity

Three observations have suggested that acid-sensing ion channels (ASICs) might be mammalian cutaneous mechanoreceptors; they are structurally related to Caenorhabditis elegans mechanoreceptors, they are localized in specialized cutaneous mechanosensory structures, and mechanical displacement generates an ASIC-dependent depolarization in some neurons. However, previous studies of mice bearing a single disrupted ASIC gene showed only subtle or no alterations in cutaneous mechanosensitivity. Because functional redundancy of ASIC subunits might explain limited phenotypic alterations, we hypothesized that disrupting multiple ASIC genes would markedly impair cutaneous mechanosensation. We found the opposite. In behavioral studies, mice with simultaneous disruptions of ASIC1a, -2 and -3 genes (triple-knockouts, TKOs) showed increased paw withdrawal frequencies when mechanically stimulated with von Frey filaments. Moreover, in single-fiber nerve recordings of cutaneous afferents, mechanical stimulation generated enhanced activity in A-mechanonociceptors of ASIC TKOs compared to wild-type mice. Responses of all other fiber types did not differ between the two genotypes. These data indicate that ASIC subunits influence cutaneous mechanosensitivity. However, it is unlikely that ASICs directly transduce mechanical stimuli. We speculate that physical and/or functional association of ASICs with other components of the mechanosensory transduction apparatus contributes to normal cutaneous mechanosensation.     

IgE immunotoxins. Effect of an IgE-ricin A chain conjugate on rat skin histamine content

Immunotoxins--toxins covalently conjugated to specific antibodies--have been studied as possible agents in the treatment of cancer. The avid binding of IgE antibodies to FcR on mast cells and basophils suggested the possible use of an IgE-immunotoxin in the treatment of malignant mastocytosis or as a method to generate mast cell-depleted animals for study. To this end, the effect of a covalent conjugate of rat myeloma IgE and ricin A chain on rat cutaneous mast cells was examined in vivo. IgE-ricin A chain was capable of binding to and sensitizing cutaneous mast cells in vivo as indicated by a bluing response to intracutaneous anti-ricin A chain. IgE-ricin A chain, given either as a single dose or, even more effectively, as two split doses, significantly reduced cutaneous histamine content for 6 to 8 days. Neither a mixture of IgE and ricin A chain that were not conjugated nor the induction of cutaneous mast cell degranulation with anti-IgE affected cutaneous histamine levels. Therefore, IgE-ricin A chain produces a prolonged depletion of cutaneous histamine levels.     

Leishmania mexicana mexicana: genetic heterogeneity of mexican isolates revealed by restriction length polymorphism analysis of kinetoplast DNA

Leishmania mexicana mexicana isolates from 23 patients with localized, diffuse, and an atypical "pseudodiffuse" form of cutaneous leishmaniasis were obtained in various endemic regions of Mexico. Restriction fragment length polymorphism analysis of kinetoplast DNA was done with nine different endonucleases in addition to an in vitro growth pattern analysis. We found that the 23 L. mexicana mexicana isolates could be consistently classified into six groups, according to the endonuclease digestion patterns obtained with HaeIII, HpaII, and MseI. Whereas localized cutaneous leishmaniasis isolates could have any of five patterns, diffuse cutaneous leishmaniasis showed only two patterns and pseudodiffuse cutaneous leishmaniasis consistently showed only one pattern. Thus, a clear correlation among digestion pattern, clinical disease, and geographical localization was obtained for the pseudodiffuse cutaneous leishmaniasis group. Additionally, the L. mexicana mexicana isolates could be differentiated into fast- and slow-growing groups. Diffuse cutaneous leishmaniasis isolates were found to be fast growing, whereas localized cutaneous leishmaniasis isolates fell into both categories. In contrast, all pseudo diffuse cutaneous leishmaniasis isolates were slow growing. Here we report the first study in which distinct and persistent genotypic characteristics of kinetoplast DNA heterogeneity within the L. mexicana mexicana species could be directly correlated with clinical disease and its growth behavior, suggesting that a distinctive restriction pattern could have important biological implications. Additionally, this study sheds new light on the biological significance of parasite kinetoplast DNA, since the heterogeneity seems not to be random but to form a distinct pattern.     

Cutaneous blood vessels in scent pigs

The purpose of this study was to systematically provide anatomic data for flap research in plastic surgery on the cutaneous blood vessels. Seven scent pigs used in this study were killed anesthetically, and their carotid vessels were intubated and injected with a black liquid rubber. Twenty-four hours later, the integument of the scent pig was removed, and the perforating points of the cutaneous vessels were recorded. The different-sized pieces of integument became transparent. Part of this transparent skin tissue was cut into cross-sectional strips. There were three types of the cutaneous vascular source, the same as in humans. Six division levels of vessels in the skin were identified, which formed five vascular plexuses and two systems (the perforating vessel system and the cutaneous vessel system). There were two sets of vein systems: the concomitant vein and the oscillating vein; the latter can be divided into regular and irregular types. The structures of the perforating vessel system and the cutaneous vessel system were the morphological basis for choosing flaps. Two anatomic points have been emphasized: the preserved vascular plexus in thin flaps (not the subcutaneous vascular network reported previously) and the dependency of vascular structure on its location. Otherwise, this study has also provided two new kinds of flaps used in experimental study: the arterial loop flap and the intermuscular septal perforator flap. Although there were differences as well as similarities in skin vasculature between humans and the scent pig, the scent pig is still suitable for flap research.     

Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review

The wide variety of Leishmania species responsible for human American cutaneous leishmaniasis combined with the immune mechanisms of the host results in a large spectrum of clinical, histopathological, and immunopathological manifestations. At the middle of this spectrum are the most frequent cases of localized cutaneous leishmaniasis (LCL) caused by members of the subgenera Leishmania and Viannia, which respond well to conventional therapy. The two pathogenicity extremes of the spectrum generally recognized are represented at the hypersensitivity pole by mucocutaneous leishmaniasis (MCL) and at the hyposensitivity pole by anergic diffuse cutaneous leishmaniasis (ADCL). Following the present study on the clinical, histopathological and immunopathological features of cutaneous leishmaniasis in Amazonian Brazil, we propose the use of the term "borderline disseminated cutaneous leishmaniasis" for the disseminated form of the disease, due to parasites of the subgenera Leishmania and Viannia, which might be regarded as intermediate between LCL and the extreme pathogenicity poles MCL and ADCL.     

花背蟾蜍和中华蟾蜍皮肤腺体及耳后腺体的组织学研究

目的了解花背蟾蜍和中华蟾蜍皮肤腺和耳后腺的显微结构特点。方法采用大体解剖学方法观察耳后腺的外部形态及皮肤分泌物特征,采用常规石蜡包埋组织切片技术、HE和PAS染色方法观察皮肤腺和耳后腺的结构。结果花背蟾蜍和中华蟾蜍相比,皮肤黏液腺和耳后腺的显微结构差异有显著性,皮肤颗粒腺结构相似,推测当颗粒腺中的分泌物排出后,腺体外的上皮肌细胞变厚,细胞界限明显。花背蟾蜍皮肤黏液腺有两类分泌细胞相间排列成花环型。根据黏液腺分泌细胞的高矮（即中等高柱状、矮柱状和极矮柱状）,中华蟾蜍皮肤黏液腺相应地可见到三种形态,第三种黏液腺的分泌细胞极矮腺腔较大,数量极少,基本上只在前后肢皮肤中观察到。花背蟾蜍和中华蟾蜍的耳后腺也有差别：一是,中华蟾蜍耳后腺中大瓶状腺体内含物明显不同;二是,中华蟾蜍耳后腺中大瓶状腺体的大导管外侧有不同腺体存在,花背蟾蜍则无;三是,中华蟾蜍耳后腺表皮下大瓶状腺体上有钙化层存在,花背蟾蜍则无。结论两种蟾蜍皮肤腺和耳后腺均存在一定的差异,这种形态结构的差异与其生活习性和防御机能密切相关。     

Indirect immunofluorescence test in New World leishmaniasis: serological and clinical relationship

The indirect immunofluorescence test (IF) for anti-Leishmania antibodies (IgG and IgM) was performed with sera from the following groups of individuals: 214 cutaneous leishmaniasis patients, 28 healthy subjects with positive Montenegro's skin test (MST), 29 healthy subjects with negative MST and 16 visceral leishmaniasis patients. The first four groups came from a suburban area of Rio de Janeiro (Jacarepaguá) where cutaneous leishmaniasis caused by Leishmania braziliensis braziliensis is endemic. It was observed that IF-IgM titers were significantly higher amongst the cutaneous leishmaniasis patients with less than four months of disease as compared to those with longer periods and that IF-IgG titers were significantly higher in patients with multiple lesions as compared to those with single lesions. The visceral leishmaniasis patients had IF-IgG titers significantly higher than those from cutaneous leishmaniasis patients. A group of 28 individuals selected amongst the 214 cutaneous leishmaniasis patients had their IF-titers (IgG and IgM) compared to those of the two control groups of healthy subjects from the endemic area, respectively with positive and negative MST. Significantly higher titers of IF-IgG and IF-IgM were found in the group with active disease. The same group of patients showed IF-IgG titers significantly lower at the end of the antimonial therapy than those observed during this treatment.     

Delayed cutaneous hypersensitivity response in tetanus toxoid sensitized rhesus monkeys: predictor of anergy and value in tuberculin skin testing

The primary problem in using the tuberculin skin test in nonhuman primates is the clinical uncertainty concerning the animal's ability to elicit a delayed cutaneous hypersensitivity response. A negative tuberculin skin test can only be meaningful if the animal can produce a delayed cutaneous hypersensitivity reaction. Veterinarians deliberately sensitize animals to antigens in the form of prophylactic vaccination. Therefore, if nonhuman primates were deliberately sensitized to an antigen capable of producing a hypersensitivity response, that antigen should serve as a positive control for delayed cutaneous hypersensitivity reactions. Tetanus toxoid was chosen because repeated immunizations with this antigen is recommended routine medical practice for nonhuman primates housed outdoors. Twenty juvenile, male rhesus (Macaca mulatta) monkeys were selected for this study. The monkeys were assigned randomly to one of two groups of ten animals. The test group was vaccinated with tetanus toxoid intramuscularly at 1 month intervals for a total of three vaccinations. The control group was treated the same except saline was administered rather than tetanus toxoid. Following sensitization, the two groups of animals were challenged with tetanus toxoid intradermally. Eight of the ten monkeys in the test group responded to the tetanus toxoid while none of the control groups responded to the tetanus toxoid. Elicitation of a delayed cutaneous response in animals sensitized to tetanus antigen before challenge may serve as a positive control for delayed cutaneous hypersensitivity. This simple test may serve as a useful adjunct in making objective clinical decisions concerning anergy-suspect animals.     

Cutaneous ligaments of the human hand

A topographical study concerning the cutaneous ligaments of adult as well as human fetal hands was performed. In order to be able to preserve the cutaneous ligaments in their entirety two different methods, a careful dissection and a new histological technique, have been employed. The results of these methods are compared and the detailed topography of the different cutaneous ligaments is clarified. In addition to topographical details, the functional co-operation of the ligaments especially in regard to their clinical relevance is reported.     

Further observations on clinical, histopathological, and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis

Leishmania (Leishmania) amazonensis has for some time been considered as the causative agent of two distinct forms of American cutaneous leishmaniasis (ACL): localized cutaneous leishmaniasis (LCL), and anergic diffuse cutaneous leishmaniasis (ADCL). Recently, a new intermediate form of disease, borderline disseminated cutaneous leishmaniasis (BDCL), was introduced into the clinical spectrum of ACL caused by this parasite, and in this paper we record the clinical, histopathological, and immunological features of eight more BDCL patients from Brazilian Amazonia, who acquired the disease in the Pará state, North Brazil. Seven of them had infections of one to two years' evolution and presented with primary skin lesions and the occurrence of metastases at periods varying from six to 12 months following appearance of the first lesion. Primary skin lesions ranged from 1-3 in number, and all had the aspect of an erythematous, infiltrated plaque, variously located on the head, arms or legs. There was lymphatic dissemination of infection, with lymph node enlargement in seven of the cases, and the delayed hypersensitivity skin-test (DTH) was negative in all eight patients prior to their treatment. After that, there was a conversion of DTH to positive in five cases re-examined. The major histopathological feature was a dermal mononuclear infiltration, with a predominance of heavily parasitized and vacuolated macrophages, together with lymphocytes and plasma cells. In one case, with similar histopathology, the patient had acquired his infection seven years previously and he presented with the largest number of disseminated cutaneous lesions. BDCL shows clinical and histopathological features which are different from those of both LCL and ADCL, and there is a good prognosis of cure which is generally not so in the case of frank ADCL.     

Primary cutaneous coccidioidomycosis; the criteria for diagnosis and a report of a case

Study was made of a case of coccidioidomycosis known to have resulted from primary inoculation of the organisms into the skin. Clinical observations and laboratory data were obtained at the time of clinical illness and for a period of five years thereafter. From the information thus obtained and correlation of it with what already was known of coccidioidomycosis, it was concluded that the disease originates very rarely as the result of primary cutaneous inoculation. In most instances lesions suspected to be of this type have actually resulted by dissemination of the organisms to the skin from a previously unrecognized pulmonary focus. Primary cutaneous coccidioidomycotic lesions closely resemble the primary cutaneous lesions (chancres) in other infectious granulomata, such as syphilis, tuberculosis and sporotrichosis. Spontaneous involution should occur within three months and then there should be immunity to reinfection in all but one or two per thousand instances. From these observations certain criteria were evolved by which to determine in a case of coccidioidomycosis with cutaneous manifestations whether or not the infecting organism entered through the skin.     

PRIMARY CUTANEOUS COCCIDIOIDOMYCOSIS—The Criteria for Diagnosis and a Report of a Case

Study was made of a case of coccidioidomycosis known to have resulted from primary inoculation of the organisms into the skin. Clinical observations and laboratory data were obtained at the time of clinical illness and for a period of five years thereafter. From the information thus obtained and correlation of it with what already was known of coccidioidomycosis, it was concluded that the disease originates very rarely as the result of primary cutaneous inoculation. In most instances lesions suspected to be of this type have actually resulted by dissemination of the organisms to the skin from a previously unrecognized pulmonary focus.Primary cutaneous coccidioidomycotic lesions closely resemble the primary cutaneous lesions (chancres) in other infectious granulomata, such as syphilis, tuberculosis and sporotrichosis. Spontaneous involution should occur within three months and then there should be immunity to reinfection in all but one or two per thousand instances.From these observations certain criteria were evolved by which to determine in a case of coccidioidomycosis with cutaneous manifestations whether or not the infecting organism entered through the skin.     

La TEP-TDM au 18FDG a-t-elle un intérêt dans la stadification ganglionnaire des mélanomes malins cutanés cervicofaciaux bénéficiant de la technique du ganglion sentinelle ? À propos de 22 cas

Background and objectivesIn N0 cutaneous head and neck melanoma, sentinel lymph node biopsy (SLNB) is less reliable and accurate than in trunk or extremities melanoma (false negative cases and spotting failure). The aim of our study was to assess the utility of PET-CT ¹⁸FDG in a specific group of N0 patients, combined with SLNB.Patients and methodsTwenty-two patients with N0 cutaneous head and neck melanoma were retrospectively reviewed. All of them had underwent PET-CT and SLNB before surgery. Average follow-up time was 17 months (1–44).ResultsAt least one sentinel lymph node (SLN) was identified in 20 patients. Ten patients (50%) had metastatic SLN. Among these 10 N+ patients, PET-CT was positive for occult nodal metastases for only two patients. During follow-up, two patients had cervical nodal recurrence, whereas SLNB was negative. PET-CT was also negative for these two patients. SLNB and PET-CT sensitivity were respectively 83 and 18%. PET-CT specificity was 84% (regarding neck sides).ConclusionIn this specific population with N0 cutaneous head and neck melanoma, PET-CT sensitivity is too low and failed to detect occult nodal metastases in two patients with false negative SLNB. Consequently, PET-CT seems to be not useful for nodal staging N0 cutaneous head and neck melanomas, in which SLNB is the most accurate technique.     

Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans.

The hypothesis that baroreceptor unloading during dynamic limits cutaneous vasodilation by withdrawal of active vasodilator activity was tested in seven human subjects. Increases in forearm skin blood flow (laser-Doppler velocimetry) at skin sites with (control) and without alpha-adrenergic vasoconstrictor activity (vasodilator only) and in arterial blood pressure (noninvasive) were measured and used to calculate cutaneous vascular conductance (CVC). Subjects performed two similar dynamic exercise (119 +/- 8 W) protocols with and without baroreceptor unloading induced by application of -40 mmHg lower body negative pressure (LBNP). The LBNP condition was reversed (i.e., either removed or applied) after 15 min while exercise continued for an additional 15 min. During exercise without LBNP, the increase in body core temperature (esophageal temperature) required to elicit active cutaneous vasodilation averaged 0.25 +/- 0.08 and 0.31 +/- 0.10 degrees C (SE) at control and vasodilator-only skin sites, respectively, and increased to 0.44 +/- 0.10 and 0.50 +/- 0.10 degrees C (P < 0.05 compared with without LBNP) during exercise with LBNP. During exercise baroreceptor unloading delayed the onset of cutaneous vasodilation and limited peak CVC at vasodilator-only skin sites. These data support the hypothesis that during exercise baroreceptor unloading modulates active cutaneous vasodilation.     

Phylogenetic significance of the skin of New World monkeys (order primates, infraorder Platyrrhini).

The combined properties of a given cutaneous system, like other characters classically employed by systematic zoologists, are useful criteria in the assessment of primate taxonomy and phylogeny. From the synthesis of all available data, it is also concluded that (1) the results define a baseline regarding the normal histology and histochemistry of the skin of most genera and many species of New World monkeys; (2) intrageneric and intraspecific subtleties in cutaneous variation exist in primate integument; (3) single and multiple cutaneous traits contribute to the characterization and accurate identification of most levels of taxa within the primate hierarchy; (4) some traits, however, negate recent taxonomic practices, e.g., the familial position of Callimico; (5) basic cutaneous patterns confirm currently accepted concepts of taxonomy and phylogeny; and (6) the various cutaneous signatures of extant platyrrhines record a history of adaptive radiation in isolation, and suggest that the designation of at least two distinct families is warranted.     

Tactile feedback plays a critical role in maximum finger force production

This study investigates the role of cutaneous feedback on maximum voluntary force (MVF), finger force deficit (FD) and finger independence (FI). FD was calculated as the difference between the sum of maximal individual finger forces during single-finger pressing tasks and the maximal force produced by those fingers during an all-finger pressing task. FI was calculated as the average non-task finger forces normalized by the task-finger forces and subtracted from 100 percent. Twenty young healthy right-handed males participated in the study. Cutaneous feedback was removed by administering ring block digital anesthesia on the 2nd, 3rd, 4th and 5th digits of the right hands. Subjects were asked to press force sensors with maximal effort using individual digits as well as all four digits together, with and without cutaneous feedback. Results from the study showed a 25% decrease in MVF for the individual fingers as well as all the four fingers pressing together after the removal of cutaneous feedback. Additionally, more than 100% increase in FD after the removal of cutaneous feedback was observed in the middle and ring fingers. No changes in FI values were observed between the two conditions. Results of this study suggest that the central nervous system utilizes cutaneous feedback and the feedback mechanism plays a critical role in maximal voluntary force production by the hand digits.     

Two imported cases of cutaneous larva migrans

Cutaneous larva migrans (CLM) is a rare serpiginous cutaneous eruption caused by accidental penetration and migration in the skin with infective larvae of nematode that normally do not have the human as their host. Although CLM has a worldwide distribution, the infection is most frequent in warmer climates. More recently, they have been increasingly imported from the tropics or subtropics by travelers. We experienced two patients who had pruritic serpiginous linear eruption in their skin for a few weeks after traveling to the endemic areas (Brazil and Thailand, respectively). After the treatment with albendazole, the skin lesions resolved with post-inflammatory hyperpigmentation. We report herein two cases of cutaneous larva migrans successfully treated with albendazole.     

Effect of in vivo aging on the growth of rat fibroblastic cells from cutaneous explants

The migration of fibroblastic cells from explants and the fibroblastic proliferation were two important parameters of healing. They were studied from animal explants of different ages and correlated with a qualitative and quantitative histologic analysis of the cutaneous tissue. These results confirm the decrease of the migration-proliferation capacity of the fibroblasts from cutaneous explants with age. This decrease was associated during maturity with a decrease of cell density in the dermis. It was no longer correlated during the passage from the adult to the senescent state. We must therefore admit an evolution in cell differentiation.