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Effect of 7,12-dimethylbenz(a)anthracene on the integument of the hibernating and nonhibernating 13-lined ground squirrel.

1. DMBA, a chemical carcinogen, was topically applied to skin patches of hibernating and nonhibernating ground squirrels (Spermophilus tridecemlineatus). 2. Macroscopically, hyperpigmentation, hair loss and excessive skin sloughing were evident in all treated nonhibernator skin patches. 3. Histological sections of skin revealed hyperkeratosis, epidermal vesicles, acanthosis, an indistinct basal layer and increased vascularization in nonhibernators. 4. Skin patches on hibernators were unaffected by treatment showing hibernation confers protection from the pathological effects of DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

Two-generation reproduction study of sulfur mustard in rats.

Comprehensive data are not available to evaluate the potential risk to reproduction from exposure to sulfur mustard (HD), [bis(2-chloroethyl) sulfide]; thus, the reproductive effects of HD were evaluated in Sprague-Dawley rats. Groups, of rats (27 females and 20 males/group/generation) were gavaged with 0, 0.03, 0.1, or 0.4 mg/kg HD 5 d/week for 13 weeks prior to mating and throughout gestation, parturition, and lactation in a 42-week, 2-generation study. Growth of adult F1 rats of both sexes was reduced by the 0.4 mg/kg exposure. There were no significant effects on reproductive function or pregnancy outcome in either generation, except for an altered sex ratio in the 0.4 mg/kg group. Although not different at birth, growth of the 0.4 mg/kg F1 and F2 offspring was depressed during lactation. A dose-related lesion of the squamous epithelium of the forestomach was observed in adults of both sexes and both the F1 and F2 generation. For a given treatment, the incidence was approximately the same for each sex at each generation. When animals were pooled by sex and generation, approximately 70% (66 out of 94) of the low dose group had only mild microscopic lesions, 72% (68 out of 94) of the intermediate dose group had moderate lesions, and 81% (76 out of 94) of the high group had marked lesions. The lesion, acanthosis, was characterized by thickening of the squamous musoca with varying degrees of hyperkeratosis. Benign neoplasms of the forestomach were found in about 10% of the intermediate and high dose groups in both F0 and F1 generations. Based on these results, the No-Observable-Adverse-Effect-Level (NOAEL) is 0.1 mg/kg/d.

Animals↗

Anti-CD4 monoclonal antibody therapy in severe psoriasis.

We report here the treatment of psoriasis, a chronic inflammatory skin disease characterized by uncontrolled keratinocyte proliferation, with BB14, a CD4 murine IgG1 antibody. Three patients with severe psoriasis were treated with anti-CD4 mAb infusions (0.2 mg/kg/day for the first patient, 0.4 mg/kg/day for 2 days and 0.8 mg/kg/day during the following days for the 2 others) for 7 or 8 days, without other therapy. Rapid clinical improvement, with major reduction of the Psoriasis Area Severity Index, was observed during 1 month after treatment. Moderate decreases in CD4+ blood cells occurred in the last two patients but not in the first one. Circulating T cells coated with anti-CD4 mAb were detectable during the first 48 h in the first patient and from day 1/2 to day 7/8 in the two others. The density of CD4 molecules on the surfaces of peripheral blood lymphocytes was decreased in all patients and remained low as long as anti-CD4 mAb was detectable in patient serum. The maximal 24 h residual mAb levels ranged from 0.3 microgram/ml in the first patient to 3.8 and 7.0 microgram/ml in the two others. The three patients produced IgM antibodies against the anti-CD4 mAb at day 7/8 or 15 and two patients had IgG antibodies at day 15. Lesional skin samples demonstrated (1) gradual improvement in parakeratosis, papillomatosis and acanthosis, (2) decreased expression of ICAM-1 and HLA-DR by keratinocytes, (3) an increase in CD1a+ Langerhans cell number, (4) partial decrease in epidermal T cell infiltrate and (5) no major change in the dermal infiltrate composed of CD3+, TcR alpha beta+, CD45Ro+, HLA-DR+ T cells. We conclude that anti-CD4 mAb administration can induce a rapid and major improvement in psoriatic lesions, with immunohistochemical changes different from those induced by cyclosporin A or 8-methoxypsoralen plus long wave UV light (PUVA) therapy. Our data provide strong evidence for a critical role of CD4+ lymphocytes in psoriasis.

Adult↗

20 MHz sonography, colorimetry and image analysis in the evaluation of psoriasis vulgaris.

For objective evaluation of the treatment of psoriasis vulgaris standard techniques are desirable. They should be reproducible, sensitive and non-invasive. In this study non-invasive bioengineering techniques, especially high frequency/high resolution ultrasound for measurement of the healing of psoriasis vulgaris were evaluated. Fifty patients with chronic stationary plaque type psoriasis participated in a prospective study; in each patient two psoriatic plaques were examined by means of sonography, colorimetry and image analysis during treatment until complete resolution had occurred. Skin thickness and density could be quantified by means of high frequency ultrasound. In active psoriatic lesions, an echopoor area underneath the entry echo in the ultrasound image caused by acanthosis and inflammatory infiltrate is typical. Under therapy the thickness of this echopoor area diminishes while its density increases. Intensity of the erythema especially the decrease of erythema through healing could not exactly be quantified with the colorimeter because the 'Lab'-CIE-colour representation system cannot distinguish well enough between the colours red and brown. Image analysis allowed to measure the sizes of the psoriatic plaques and to quantify their resolution under therapy. The measuring of plaque size by the aid of computer based image analysis is possible and useful.

Colorimetry↗

The effect of anti-CD4 monoclonal antibody treatment on immunopathological changes in psoriatic skin.

Recent clinical studies which showed the therapeutic effect of cyclosporin A and of anti-CD4 MoAb emphasized the role of activated CD4+ T cells infiltrating the lesional skin in the pathogenesis of psoriasis. The aim of the present study was to analyze the mode of action of anti-CD4 MoAb in 3 psoriatic patients who experienced an anti-CD4 MoAb-induced clinical improvement maximal 3-4 weeks after the onset of an 8-day therapy. We evaluated the effect of anti-CD4 MoAb treatment on the phenotype of resident and passenger inflammatory skin cells in lesional skin samples. We observed a gradual improvement of 3 out of 4 histopathologic features including parakeratosis, papillomatosis and acanthosis. In the dermis there was no modification in the density of the dermal mononuclear cell infiltrate, which consisted mainly of CD3+, CD45RO+, TCR alpha beta+, CD11a+, HLA-DR+T cells with a CD4/CD8 cell ratio of 1.5/1. Therefore as previously observed for peripheral blood mononuclear cells, the number of CD4+ T cells infiltrating the dermis remained unaffected by the treatment. In contrast, CD4 MoAb treatment was associated with drastic changes in the epidermis. These included a decrease in both CD4+ and CD8+ epidermal T cell infiltrate, diminished numbers of ICAM-1+ and HLA-DR+ keratinocytes and restored numbers of CD1a+ epidermal Langerhans cells. We conclude from this study that clinical improvement of psoriasis by anti-CD4 MoAb therapy paralleled: (1) a decrease in epidermal T cells, and (2) a down-regulation of keratinocyte activation markers (ICAM-1 and HLA-DR). These results suggest that the observed changes are secondary to down-regulation of inflammatory cytokine production by T cells in situ.

Adult↗

Hirsutoid papillomas of vulvae: absences of human papilloma virus (HPV) DNA by the polymerase chain reaction.

We have analyzed the specimens from 16 women with hirsutoid papillomas of the vulvae for the presence of HPV DNA using the polymerase chain reaction. The subjects' ages ranged from 27 to 43 years. In all cases, smooth or filiform papules were symmetrically located on the inner surface of both labia minora. Histologically, the lesions consist of acanthosis or papillomatosis without koilocytes and mitotic activity. Eight of 16 specimens were studied by transmission electron microscopy (TEM). No HPV granules were found in the nuclei of keratinocytes. HPV DNA could not be detected in all specimens. Positive controls were present in each assay. These results suggest that the papules of hirsutoid papillomas of the vulvae are unrelated to HPV. Chronic irritants and inflammation may play an important role in pathogenesis.

Adult↗

Flow cytometric analysis of pig epidermal keratinocytes: effects of ultraviolet B irradiation (UVB) and topical PUVA treatment.

The effects of a single application of ultraviolet B irradiation (UVB) and topical PUVA treatment on pig epidermal cell kinetics were studied by DNA-flow cytometry (FCM), 3H-thymidine uptake, mitotic counts and 2-3H-deoxy-D-glucose uptake. Following UVB irradiation (2MED: 250 mJ/cm2) and PUVA (0.9, 1.4 J/cm2) treatment, thymidine uptake and mitosis were markedly decreased. This was followed by a transient increase in all of these parameters. The maximal increase was observed at 96 h following the UVB irradiation and at 168 h following the PUVA treatment (0.9 J/cm2), respectively. The suppression of DNA synthesis and mitosis persisted for a longer period in PUVA-treated than in UVB-treated epidermis. At 48-72 h after the UVB irradiation and 72-144 h after the PUVA treatment, an increase in the cells of the G2/M fraction was observed. This was associated with the decreased mitotic counts, suggesting accumulation of G2-blocked cells. Histologically, PUVA-treated epidermis showed a considerable degenerative change. Mild acanthosis was noted at 72-96 h in UVB-treated epidermis and at 168 h in PUVA-treated epidermis. These results indicate that the inhibition of DNA synthesis and increase in G2-phase cells are associated with the UVB and PUVA induced suppression of epidermal cell proliferation. These suppressive effects that persisted longer in PUVA-treated, than in UVB-treated epidermis, were followed by an increased epidermal keratinocyte proliferation of pig skin in vivo.

Animals↗

Colocalization of scavenger receptor in CD68 positive foam cells in verruciform xanthoma.

Verruciform xanthoma is a rare variant of xanthoma that appears predominantly on oral mucosa and the anogenital area. The histologic features are characterized by marked accumulation of foam cells in the papillary dermis with verrucous epidermal acanthosis and hyperkeratosis. However, little is known of the nature or origin of foam cells. Recent studies have emphasized the crucial role of macrophage scavenger receptors in the formation of foam cells in atherogenesis. We examined the immunohistologic localization of scavenger receptors in genital verruciform xanthoma. We found that the massively infiltrated foam cells in the papillary dermis were CD68+ monocyte-macrophage lineage cells, and that the majority of CD68+ cells coexpressed scavenger receptors. The in situ staining pattern of scavenger receptor in foam cells was mainly of an intracytoplasmic vacuolar pattern similar to that of dermal resident macrophages found in normal skin. Furthermore, CD1a+ Langerhans cells, completely negative for scavenger receptor, were markedly decreased in number in verruciform xanthoma. These results indicate that scavenger receptor-bearing CD68+ cells are also actively involved in the development of cutaneous verruciform xanthoma, as has been shown to be the case in atherogenesis.

Aged↗

Oral florid papillomatosis.

A case of oral florid papillomatosis involving the superior and inferior alveolar ridges, the palate and the tongue in a young woman is presented. Histological examination showed papillary hyperplasia with marked acanthosis. The basement membrane remained intact. The patient was treated with a combination of recombinant-alpha 2a interferon and carbon dioxide laser surgery.

Adult↗

The insulin resistant subphenotype of polycystic ovary syndrome: clinical parameters and pathogenesis.

OBJECTIVE: This study was undertaken to compare clinical and biochemical characteristics of the insulin resistant (IR) and non-IR subphenotypes of polycystic ovary syndrome (PCOS). STUDY DESIGN: Infertile PCOS women were classified as IR (n=32) or non-IR (n=46) on the basis of fasting glucose and insulin levels. The incidence of acanthosis nigricans (AN), hirsutism, and ovulation in response to clomiphene citrate (CC) was compared between the 2 groups, along with serum levels of gonadotropins, and sex steroids. Blood samples from 28 PCOS patients and 8 controls were analyzed by enzymatic immunoassay for autophosphorylated insulin receptor (APIR) and total insulin receptor (TIR) content. RESULTS: Insulin resistance was associated with obesity (odds ratio [OR]=3.5, P <.05), AN (OR=6.0, P <.05), hirsutism (OR=3.1, P <.05), and resistance to CC (OR=5.0, P <.05). Mean levels of LH, LH/FSH ratios, and testosterone were lower in women with IR (11.5 +/- 6.8 mIU/mL, 2.0 +/- 1.0, and 56.6 +/- 29.0 ng/dL, respectively) compared with women without IR (15.0 +/- 13.4 mIU/mL, 2.4 +/- 1.5, and 72.5 +/- 29.8 ng/dL, respectively) (P <.05). Mean APIR/TIR ratios in IR women were lower than in non-IR women (P <.05 at 100 nmol/L of insulin) and controls (P <.01 at 1, 10 and 100 nmol/L insulin). CONCLUSION: Patients with IR are more likely to be obese and have AN, hirsutism, resistance to CC, and lower LH, LH/FSH ratios, and testosterone levels. Furthermore, IR patients appear to have defective autophosphorylation of the insulin receptor, a key element in insulin action, and a possible mechanism for IR in PCOS.

Adult↗

The prevalence of androgen excess among patients with minimal unwanted hair growth.

OBJECTIVE: The prevalence of androgen excess (AE) and the value of preemptive endocrine evaluation in women with minimal unwanted hair growth are unclear. SUBJECTS: A total of 228 patients presented with minimal unwanted hair growth and a mF-G score of 5 or less. Total and free testosterone, dehydroepiandrosterone sulfate, 17-hydroxy-progesterone, sex hormone-binding globulin, and basal insulin and glucose levels were measured. RESULTS: Of the patients, 54% demonstrated an AE disorder (50%: polycystic ovary syndrome, 2%: hyperandrogenic insulin-resistant acanthosis nigricans syndrome, 2%: nonclassic adrenal hyperplasia), 29% isolated oligoovulation, 6% isolated hyperandrogenemia, and 10% had a normal evaluation. Of the patients with menstrual irregularities, 65% had an underlying AE disorder compared with 22% of those with normal menstrual function ( P < .001). Of eumenorrheic patients, 11% had oligo-ovulation and an AE disorder. CONCLUSION: Patients with minimal unwanted hair growth should be evaluated endocrinologically because approximately 50% of subjects demonstrate an AE disorder. Eumenorrhea does not preclude an underlying AE disorder, and ovulatory function should be assessed in these women.

Age Distribution↗

[Anorectal Buschke-Lowenstein tumor. (Three cases report)].

Buschke-Lowenstein tumor or giant condyloma acuminata is characterized by a proliferation locally aggressive with extensive tissue destruction. We report three cases of Buschke-Lowenstein tumor with anorectal localization. The histology is characterized by papillomatosis and endo or exophytic acanthosis secondary to papillomavirus. The variety of treatment regimens applied do not allow formulation of definitive therapeutic guidelines.

Adult↗

[Weight of obesity in (pre)type 2 diabetes in children and adolescents: how and when to screen for?].

There has been wide recognition in the past decade of the increasing frequency of type 2 diabetes in youth, largely but not exclusively in North America. In some American locations and populations, incidence and prevalence of type 2 diabetes are much higher than those of type 1 diabetes, because of increased calorie and fat intake, and decreased exercise. The increasing prevalence of type 2 diabetes in the United States has closely paralleled the increase in childhood obesity noted there, but now across the Western world. Besides obesity, the other youth risk factors for type 2 diabetes are: ethnicity, puberty, family history, metabolic syndrome, polycystic ovary syndrome, acanthosis nigricans. Any feature or condition associated with insulin resistance/hyperinsulinemia should alert to screen youth at increased risk for (pre)type 2 diabetes. Treatment goals are to decrease weight and increase exercise, to normalize insulinemia, glycemia and HbA1c, to control hypertension and hyperlipidemia. The aim of the pharmacological therapy is to decrease insulin resistance, namely by metformin. Sometimes, insulin therapy is necessary.

Adolescent↗

Transgenic rats overexpressing the human MrgX3 gene show cataracts and an abnormal skin phenotype.

The human MrgX3 gene, belonging to the mrgs/SNSRs (mas related genes/sensory neuron specific receptors) family, was overexpressed in transgenic rats using the actin promoter. Two animal lines showed cataracts with liquification/degeneration and swelling of the lens fiber cells. The transient epidermal desquamation was observed in line with higher gene expression. Histopathology of the transgenic rats showed acanthosis and focal parakeratosis. In the epidermis, there was an increase in cellular keratin 14, keratin 10, and loricrin, as well as PGP 9.5 in innervating nerve fibers. These phenotypes accompanied an increase in the number of proliferating cells. These results suggest that overexpression of the human MrgX3 gene causes a disturbance of the normal cell-differentiation process.

Animals↗

Life-threatening paraneoplastic cutaneous syndromes.

Paraneoplastic syndromes are diseases or symptom complexes associated with malignancy, usually internal. In dermatology, we modify the definition to refer to dermatoses associated with internal malignancy. In this article, we discuss the link between malignancy and such dermatologic disorders as acanthosis nigricans, acrokeratosis paraneoplastica of Bazex, dermatomyositis, erythema gyratum repens, necrolytic migratory erythema (glucagonoma syndrome), and paraneoplastic pemphigus and discuss, where such information is known, the mechanism by which these paraneoplastic diseases occur.

Critical Illness↗

Dermatology of androgen-related disorders.

Hyperandrogenism in women can be caused by various conditions, the most prevalent of which is polycystic ovary syndrome. Common dermatologic manifestations of hyperandrogenism include hirsutism, acne, acanthosis nigricans, and androgenic alopecia. Hirsute women often have increased activity of 5 alpha-reductase, the enzyme that converts the androgen testosterone to its active metabolite, in hair follicles. Likewise, androgens affect the formation of acne by increasing sebum production from sebaceous glands in the skin. The diagnosis of polycystic ovary syndrome includes a complete history, physical examination with emphasis on evidence of androgen excess, and appropriate laboratory investigation to exclude other causes of hyperandrogenism. Treatments for the dermatologic conditions of hyperandrogenism include lifestyle modification, oral contraceptives, antiandrogens, and insulin-sensitizing medications.

5-alpha Reductase Inhibitors↗

Diabetes mellitus.

Dermatologic problems are common in diabetes, with approximately 30% of patients experiencing some cutaneous involvement during the course of their illness. Skin manifestations generally appear during the course of the disease in patients known to have diabetes, but they may also be the first presenting sign of diabetes or even precede the diagnosis by many years. The skin involvement can be autoimmune in nature, such as acanthosis nigricans, necrobiosis lipoidica, diabetic dermopathy, scleredema, and granuloma annulare, or infectious in the form of erythrasma, necrotizing fasciitis, and mucormycosis. Pharmacologic management of diabetes, in addition, can also result in skin changes, such as lipoatrophy and lipohypertrophy, at the site of injection of insulin, and oral antidiabetic agents can cause multiple skin reactions as adverse effects. The management of these cutaneous manifestations is tailored according to the underlying pathophysiology, but a tight control of blood glucose is a prerequisite in all management strategies.

Blood Glucose↗

Skin manifestations in acromegaly.

Cutaneous changes in acromegaly result from excess GH and IGF-1 action on skin cells and adnexae. Skin puffiness due to dermal glycosaminoglycan accumulation and edema are most prominent in the face, hands and feet. Oily skin with large pores, hypertrichosis, and excessive sweating are common features. Pigmented skin tags, acanthosis nigricans, and psoriasis are also encountered. Alteration in skin capillaries produce increased vasoconstriction. Discerning these changes contributes to early diagnosis and treatment of this high-morbidity disorder. Controlling GH and IGF-1 over-secretion alleviates most cutaneous manifestations of acromegaly; however, regression may be incomplete.

Acromegaly↗