Alterations in the metabolism of filaggrin in the skin after chemical- and ultraviolet-induced erythema

We have investigated the effect on the normal synthesis and metabolism of filaggrin of treatment of guinea pig skin with a chemical irritant, hexadecane, or with erythemal doses of UV radiation. Examination of the skin by immunofluorescence with an antiserum against filaggrin demonstrates 3 phases of the response. The first phase is an apparent stabilization of the filaggrin present at the time of treatment. Thus, a zone of stratum corneum is produced which moves up toward the skin surface over the days following treatment, without the loss of immunoreactivity which normally results from the metabolism of filaggrin to free amino acids. The second phase of the reaction, which occurs during the first day after treatment, is a loss of immunoreactive material from the upper viable epidermis, which results over the next day in the formation of a zone of filaggrin-deficient stratum corneum. The third phase, 2-3 days after the treatment, is the reestablishment of immunoreactivity in the newly re-formed granular layer, followed by the formation of an immunoreactive zone at the bottom of the stratum corneum. This zone remains very thin despite the rapid passage of cells through it. This shows that the filaggrin being formed during this phase of the reaction is being broken down normally as the stratum corneum matures. Investigations of the kinetics of filaggrin synthesis and breakdown using a [3H]histidine pulse/chase method, confirm the impression gained from immunofluorescence studies that the time between formation and breakdown of the filaggrin is much reduced in the hyperplastic epidermis resulting from the irritation. Thus, although the hyperplasia is reflected in a thickening of malpighian and granular layers of the epidermis, it does not result in any thickening of the filaggrin-positive zone at the bottom of the stratum corneum. This suggests the action of a control mechanism designed to prevent the extension of this filaggrin-positive zone into the upper stratum corneum.     

CONGENITAL ONYCHODYSPLASIA OF THE INDEX FINGERS

Two cases of congenital onychodysplasia of the index fingers (COIF), one of them with an abnormal range of active motion of the digits, were reported. The characteristic location of a nail, or nails in micronychia and polyonychia of COIF and the involvement of the nail and the bone may be explained by the anatomy of the digit. That is, the radially more pronounced involvement of the nail may be related to the relatively smaller size of the artery of the radial aspect. This may support the transient ischemia theory of Ohta and Haseda (1) in fetal life, though the true etiology of COIF still remains obscure.     

A comparative study of the results of phlebotomy therapy and low-dose chloroquine treatment in porphyria cutanea tarda

Longer remissions after the phlebotomy therapy than after the low-dose chloroquine treatment were ascertained by means of the long-term follow-up of a large group of porphyria cutanea tarda patients. An attempt to prove the dependence of the length of laboratory and clinical remission on the values of initial porphyrinuria, on the degree of morphological liver changes, and on the total amount of blood withdrawn at phlebotomy was unsuccessful. On the contrary, a direct relationship was observed between the length of remission and the age of the subject on commencing treatment. At the same time, it was impossible to prove a causal relationship between the length of remission and initial porphyrinuria, the degree of morphological liver changes, and the total dose of drug taken, in the group of patients on the low-dose chloroquine therapy.     

Laugier-Hunziker syndrome: a clinical, histopathologic, and ultrastructural study of four cases and review of the literature.

Four cases of Laugier-Hunziker syndrome are described. In all patients (two men and two women between 39 and 57 years of age) pigmentation of the lower lip and hard palate was found. in addition, two patients had involvement of the buccal mucosa; another patient also had pigmentation of the upper lip, the gums, the soft palate, and the fingers of both hands. Histopathologic examination demonstrated an accumulation of melanin in the basal layer keratinocytes and an increase in the number of melanophages in the papillary dermis. Ultrastructural study showed the presence of numerous mature melanosomes in the cytoplasm of the keratinocytes of the basal layer and of the melanophages in the papillary dermis. Alterations of the melanocytes were not observed.     

Clinicopathologic features of epidermal cysts of the sole: comparison with traditional epidermal cysts and trichilemmal cysts

BACKGROUND: It has been described that the etiology of epidermal cysts on acral skin is different from that on non-acral skin; however, no papers have been published regarding the detailed histological differences between acral and non-acral epidermal cysts. In this study, we compared the clinicopathologic findings of epidermal cysts of the sole with those of traditional epidermal cysts and trichilemmal cysts. METHODS: The cases studied were 12 epidermal cysts of the sole, 35 traditional (non-acral) epidermal cysts, and 12 trichilemmal cysts. The age and sex of the patients and the site, size, and microscopic findings of the lesions were evaluated.The pattern of keratinization was specifically focused on the evaluation of microscopic findings. RESULTS: Microscopically, most of the epidermal cysts of the sole showed the presence of parakeratosis and focal lack of a granular layer at least at the upper portion of the cyst wall. The cyst content of the epidermal cysts of the sole was predominantly compact orthokeratotic material. These pathological findings could be explained by the pathogenesis of epidermal cysts of the sole, namely invagination of the surface epidermis. CONCLUSION: Our study indicates that most cases of the epidermal cyst of the sole are considered to be a true traumatic epidermal inclusion cyst.     

Combination effects of cosmetic moisturisers in the topical treatment of acne vulgaris

Cosmetic moisturisers were applied to one side of the face of 18 male Japanese patients with acne vulgaris who were treated with a topical administration of adapalene and clindamycin phosphate gels. We assessed the alleviating effect of the moisturisers on the side effects of the treatment. The severity of acne and the number of inflammatory and non-inflammatory lesions were measured at 0, 2, and 4 weeks. The water content in the stratum corneum and transepidermal water loss were measured by comparing the moisturiser-treated and untreated sides of the face. The sensation of skin dryness and irritation on both sides of the face were assessed by the subjects. We observed that the use of moisturisers did not impact the efficacy of the standard topical treatment and they significantly improved the water content in the stratum corneum and the sensation of dryness. These results suggested that the use of moisturisers in combination with the standard topical treatment may improve adherence to therapy by alleviating the sensation of dryness.     

The clinical features of late onset acne compared with early onset acne in women

Background Little is known about the clinical characteristics of acne based on the age of onset. Objectives The aim of this study was to investigate the clinical characteristics of patients according to the age of onset of acne and evaluate whether the findings were related to regional differences in the density of Propionibacterium acnes or the levels of sebum secretion. Methods A total of 89 women were recruited. The acne lesions were assessed by counting the lesions using standard digital photographs. Digital fluorescent photography for the evaluation of the density of P. acnes were taken and quantitative measurements of facial sebum secretion were performed. Results In women with acne, the age of onset was negatively correlated with the number of comedones and the proportion of comedones. By comparing the number of comedones and the proportion of comedones, onset of acne after 21 years of age was defined as late onset acne. In the patients with late onset acne, the number of comedones, the total number of acne lesions and the proportions of comedones were significantly less than in the patients with early onset acne. However, there were no significant differences in the fluorescence density of P. acnes or the level of sebum secretion between the two groups. Conclusions The results of this study, using objective evaluation tools, suggest that late onset acne has different clinical characteristics. Other possible factors might explain the clinical differences in late onset acne.     

雄激素受体基因CAG多态性与痤疮中医分型的相关性研究

目的探讨雄激素受体基因CAG多态性与痤疮中医分型的相关性。方法应用PCR方法扩增,对肝郁气滞型和痰瘀热结型痤疮患者的阳性PCR产物进行测序,测序结果使用澳大利亚生物数据库W eb Angis分析。结果肝郁气滞型痤疮患者的雄激素受体基因CAG微卫星片段长度的平均值是23.87±2.97;痰瘀热结型痤疮患者的雄激素受体基因CAG微卫星片段长度的平均值是20.43±2.98,两型间进行比较雄激素受体基因CAG微卫星片段的长度的平均值有显著性差异(P<0.05)。结论雄激素受体基因CAG多态性与痤疮中医分型有关。     

The immune status of patients with foot mycosis and eczema

Thirty-five patients with squamous-hyperkeratotic mycoses and onychomycoses were examined, as were 68 ones with exudative mycoses of the soles and 97 ones with disseminated eczemas. The following tests have been employed in the study: direct and indirect leucocyte migration inhibition, investigation of the lymphocyte functional activity, skin test with fungal antigen, quantitation of the absolute counts of lymphocytes, neutrophils and phagocytizing neutrophils, T and B rosette forming cells. Patients with mycoses of the soles with involvement of the nail plates, as well as those suffering from eczemas combined with mycoses developed a most marked reduction of the activity of the leukocyte migration inhibition factor (LMIF) and of the T lymphocyte mediator activity in the presence of the fungal antigen. The studies have detected the pattern of the leukocyte phagocytic reaction disturbances in the patients with mycoses and eczemas of the soles. No inhibiting effect of LMIF on the leukocytes in these patients appears to be due to the defect of the target cells and not of the producer cells. The direct and indirect leukocyte migration inhibition tests are recommended to be included in the complex of immunologic tests used in examinations of patients with exudative mycoses and eczemas of the soles and with the transitional and combined forms of these two conditions.     

The measurement of the cell cycle time in squamous epithelium using the metaphase arrest technique with vincristine

In squamous epithelia with a single layer of germinative cells, the age distribution of cells in the cell cycle is shown to depend on the direction of the mitotic axis (i.e. a line joining the nuclei of daughter cells) relative to the plane of the basal layer. When axes are in the plane of the basal layer the age distribution is exponential; when cells divide at right angles to the plane of the basal layer, the age distribution is rectangular. When there is a ratio of vertical to horizontal axes, the age distribution is intermediate but can be calculated from knowledge of the proportion of axes in the plane of the layer. Squamous epithelia can be classified according to this arrangement of axes. When there are multiple layers of germinative cells, as in psoriasis, the age distribution is shown to be exponential to a good approximation, whatever the direction of the mitotic axes in the several layers. The importance of these observations is demonstrated by analysing metaphase arrest experiments with vincristine in the single layer of germinative cells in the mouse oesophagus, and in the several layers found in psoriatic epidermis. Choice of the wrong age distribution leads to an error of 6 h in the oesophagus and 23 h in psoriatic epidermis, when the mean cell cycle time is calculated. It is concluded that, in squamous epithelium, it is most important to know the age distribution before calculating the cell cycle time by methods involving measurement of the rate of entry of cells into mitosis or DNA synthesis.     

Electrophysiological characterization of human keratinocytes using the patch-clamp technique

The living, not-cornified part of the epidermis consists mainly of keratinocytes. The control mechanisms of proliferation and differentiation are only partly understood. Similarly, the influence of ionic channels of the cell membrane on the proliferation of keratinocytes remains unclear. Preliminary investigations point to a relation between the opening of ionic channels and keratinocyte proliferation. Therefore, voltage clamp experiments were performed to gain further knowledge of the electrophysiological characteristics of human keratinocyte cellular membranes. In-vitro cultured keratinocytes of the cell line HaCaT were characterized by means of the voltage-clamp technique. As measured in the whole-cell configuration, changing the extracellular K+ or Cl--concentration shifted the membrane potential of HaCaT cells. Application of the patch-clamp-technique in the cell-attached and inside-out configuration revealed an ionic channel with a conductance of multiples of 200 pS. The reversal potential of the single channel current was shifted by substituting of intracellular Cl- by aspartate-. Channel openings disappeared after addition of 0.1 mM of the anion channel blocker 4',4' diisothiocyanato-stilbene-2-2' disulfonic acid (DIDS). It is concluded that this channel contributes to the Cl--conductance of the cellular membrane and is a determinant of the membrane potential of human keratinocytes. This channel may represent a target for pharmacological manipulation of the membrane potential and possibly the growth of human keratinocytes in dermatological proliferation disorders.     

Regulation of melanogenesis through phosphatidylinositol 3-kinase-Akt pathway in human G361 melanoma cells

The involvement of the phosphatidylinositol 3-kinase pathway in the regulation of melanogenesis was examined using human G361 melanoma cells. In the cells treated with wortmannin, a potent inhibitor of phosphatidylinositol 3-kinase, the melanin content increased concomitant with the elevated protein level of tyrosinase, a key enzyme in melanogenesis. Northern blot analysis revealed that the mRNA level of tyrosinase increased transiently on treatment of the cells with the phosphatidylinositol 3-kinase inhibitor. When the cells were infected with the adenovirus vector encoding the mutant adapter subunit of phosphatidylinositol 3-kinase, which acts as a dominant negative of phosphatidylinositol 3-kinase, both the melanin content and the expression of tyrosinase increased. In cells infected with the adenovirus vector encoding the constitutively active mutant of the lipid kinase, a decrease in melanin content as well as reduced expression of tyrosinase was observed. In cells expressing the constitutively active mutant of the serine-threonine protein kinase Akt, one of the downstream targets of phosphatidylinositol 3-kinase, the melanin content decreased as in the cells overproducing the constitutively active mutant of phosphatidylinositol 3-kinase. These results indicate that phosphatidylinositol 3-kinase regulates melanogenesis by modulating the expression of tyrosinase, and that activation of Akt is sufficient for suppression of melanin production in G361 melanoma cells.     

Immunity in syphilis]

Following a brief review of the characteristics of the causative organism of syphilis, its maintenance in laboratory animals and its relationship to the treponemes of the tropical treponematoses, consideration is given to the immune reactions and the development of antibodies to the treponeme of syphilis. The individual tests used in the diagnosis of syphilis, especially the complement fixation reactions and the flocculation tests, as well as the reactions employing specific antigens, such as the Treponemal Immobilisation Test (TPI), the Reiter Protein Complement Fixation Test (RPCFT), the Fluorescent Treponemal Antibody Test (FTA-ABS) and the Treponema Pallidum Haemagglutination Assay (TPHA), are discussed in detail. An evaluation of the results of the tests and the possible sources of errors are considered. The problem of the persistence of treponemes after clinically successful treatment is analysed and existing literature reviewed. The paper ends with a discussion of existing knowledge on protective immunity against infection with Treponema pallidum and a reminder of the need for further research into the immunology of syphilis.     

Mechanisms of selective toxicity of metronidazole and other nitroimidazole drugs.

The selectively toxic effect of nitroimidazole drugs towards anaerobic bacteria and protozoa depends on a number of factors. The killing action of such drugs as metronidazole requires the reduction of the nitro group, a process which influences the rate of entry of the drug into the susceptible cell and which is determined by mechanisms involving ferredoxin-linked (or the equivalent) reactions in the cell. The reduced agent subsequently causes strand breakage of DNA, the extent of which depends on the A + T content of the DNA. Other effects of such drugs may include the possible inhibition of DNA repair mechanisms which exacerbate DNA damage, Inhibition of activity of nitroimidazoles may be caused by aminothiol radical scavengers and radioprotectors normally present in the cell or by the presence of other organisms in the environment (that is, the vagina) capable of inactivating the drugs.     

Blue macules of localized argyria caused by implanted acupuncture needles. Electron microscopy and roentgenographic microanalysis of deposited metal

Acupuncture needles implanted in the skin for more than ten years caused peculiar bluish macules, each of which clinically resembled a blue nevus in the extremities of a 63-year-old Japanese woman. Histologically, the involved skin showed deposition of fine brownish granules in the basement membrane of the eccrine sweat glands, on the inner surface of the blood vessel walls, and along elastic fibers of the superficial dermis in addition to sparse deposits noted throughout the dermis. Electron microscopy revealed deposits of electron-dense particles on the basal lamina of the secretory coils of the eccrine sweat glands, below the basal lamina of the dermoepidermal junction, and on elastic fibers. Roentgenographic microanalysis of the involved skin demonstrated that most of the granules consisted of silver and chloride; silver was a major component in the removed needles.     

Syringocystadenoma papilliferum in an unusual location beyond the head and neck region: a case report and review of literature

A case of syringocystadenoma papilliferum with multiple papulonodules in a linear fashion located in an unusual location of the right lower abdomen is presented. The presence of a large tumor at the inferior pole raised the suspicion of malignant transformation and the presence of discharge from the lesions raised the possibility of necrosis. However, histopathological examination showed the classical features of syringocystadenoma papilliferum without malignant transformation or tumor necrosis. The patient refused to undergo surgical excision of the nodules and subsequently was lost to follow-up. This case illustrates the atypical location of a rare disease and adds to the differential diagnosis of linear verrucous lesions on the abdomen. Review of all the cases with syringocystadenoma papilliferum outside the head and neck region in the English literature showed only one case of syringocystadenoma papilliferum arising on the abdomen; our patient is the second reported case with the unique feature of linear arrangement of lesions.     

Isotretinoin and Tetracycline in the Management of Severe Nodulocystic Acne

Abstract: Thirty patients with treatment-resistant cystic and conglobulate acne entered a randomized double-blind protocol. testing the efficacy of isotretinion versus tetracycline. After 16 weeks of isotretinoin treatment, the mean number of cysts decreased by 64% and the mean sum of the longest diameters was reduced by 68%. After 16 weeks of tetracycline therapy, the total number of cysts showed a mean decrease of 52%, and the mean sum of the longest diameters decreased by 60%. The reduction in the number of cysts and the sum of their longest diameters that occurred after 16 weeks of treatment was statistically significant for each of the treatment groups, but there was no statistically significant difference between the treatment groups at the end of therapy. Eight weeks after the discontinuation of treatment in the isotretinoin group, there was an overall reduction from baseline of 82% in the cyst count and 88% in the sum of the longest diameters. In the tetracycline treatment group, the overall reduction from baseline in the cyst count was 54% and in the sum of the longest diameters, 60%. This led to a statistically significant difference in the two treatment groups, at 24 weeks. All patients on isotretinoin experienced side effects that were primarily related to the integumentary system but necessitated discontinuation of the drug for a short period of time in only one patient. Long-term followup, 8 months after discontinuation of the study, showed a prolonged significant remission of acne in the isotretinoin group but not in the tetracycline group.     

Molecular biology and pathology of type VII collagen.

Type VII collagen is a genetically distinct member of the collagen family of proteins. Type VII collagen has been shown to be the major component of anchoring fibrils, attachment complexes which secure the cutaneous basement membrane of the skin to the underlying dermis. Understanding of the structure of type VII collagen has been advanced by recent cloning of the corresponding gene. Chromosomal mapping of the gene to the short arm of chromosome 3 and identification of intragenic polymorphic markers have allowed demonstration of strong genetic linkage between the type VII collagen locus and the dystrophic forms of EB (epidermolysis bullosa). This overview summarizes the progress made in the molecular genetics of type VII collagen.     

The stigmata of late congenital syphilis: an analysis of 100 patients

Analysis of the stigmata of congenital syphilis in two study populations indicates that the imprints of the disease are the same, whether the patient population is of Caribbean or of North American origin. If the Columbian theory of origin of syphilis were correct, the longer syphilization of the West Indies might have tended to lessen the effects of the disease by attenuating Treponema pallidum. The presence of yaws and pinta in the West Indies may even have had an immunizing effect. The similar findings in the two population groups suggests that the events postulated by the Columbian theory did not take place.     

Nail changes in epidermolysis bullosa: clinical and pathogenetic considerations

Nail changes in epidermolysis bullosa (EB) are common, but although they are highly suggestive of the disease, they are not pathognomonic. They are the result of abnormalities of the nail matrix and nail bed, associated with the pathogenetic alterations of the dermo-epidermal junction which occur in EB. In addition, secondary trauma in the areas of epidermal-dermal separation, and chronic inflammation of the nail matrix, are probable contributory factors, even in non-scarring forms of EB. Recent developments in the molecular and cell biology of the cutaneous basement membrane zone have greatly advanced our understanding of the pathomechanisms underlying different subtypes of EB. Defects in genes coding for the structural proteins of the basement membrane zone have been defined in some EB subtypes, and abnormal expression of structural proteins in others. The data accumulated from study of these genetic disorders will contribute to knowledge of the role of the dermo-epidermal junction in the normal physiology and differentiation of the nails, and be of value n discerning the aetiopathogenesis of acquired nail diseases.