Construction of Tn917ac1, a transposon useful for mutagenesis and cloning of Bacillus subtilis genes.

A Tn917 derivative was constructed for the purposes of mutagenesis and cloning of Bacillus subtilis genes. This transposon, Tn917ac1 (4.6 kb), consisted of terminal inverted repeats of Tn917, the res sequence, a ColE1 origin of replication (ori) and two drug-resistance genes. The plasmid carrying this transposon, named pD917, contained the erm-tnpR-tnpA gene cluster of Tn917 and a temperature-sensitive ori of pE194. For the purpose of mutagenesis, transposition of Tn917ac1 was induced by culturing strains harboring pD917 in a medium containing a low concentration of erythromycin. Cells with a Tn917ac1 insertion in the chromosome were selected on agar containing chloramphenicol after heat treatment to eliminate the plasmidic form of pD917. DNA fragments adjacent to Tn917ac1 could be cloned by restriction digestion of the chromosomal DNA and by transforming the self-ligated restriction fragments into Escherichia coli. Sequence analysis revealed that Tn917ac1 was integrated into the chromosome of B. subtilis by transposition in a recE strain and by transposition or integration of pD917 in a wild-type strain. Tn917ac1 has been demonstrated to be useful for mutating and cloning of the genes involved in the biosynthesis of fengycin in B. subtilis F29-3.

The juxtaoral organ of Chievitz.

Juxtaroral organs were found in 14 of 25 consecutive autopsies in adults who did not have carcinoma or other lesions of the oral mucosa. Nearly all of the epithelium was squamous-like, but an occasional lumen was present, lined with cuboidal cells. Small nerves were intimately associated with the epithelial component. Awareness of this normal structure may be crucial in preventing unnecessarily extensive surgery should it be misinterpreted as perineural invasion by carcinoma.

Cutaneous manifestations of histoplasmosis in the acquired immune deficiency syndrome.

The clinical and histologic features of cutaneous histoplasmosis in three patients with acquired immunodeficiency syndrome (AIDS) are described. The patients presented with multiple discrete papules on the extremities, trunk, and face, some of which were follicular. Histologically, the skin biopsies were characterized by a sparse perivascular infiltrate with polymorphonuclear leukocytes, lymphocytes, and occasional histiocytes. Prominent leukocytoclasia and associated dermal necrosis were seen around the superficial blood vessels of the dermis. The Histoplasma capsulatum organisms were for the most part extracellular and difficult to visualize on the hematoxylin and eosin-stained sections. A diagnosis of atypical leukocytoclastic vasculitis was considered. Histoplasmosis is a relatively common mycosis among AIDS patients, and it is sometimes the first manifestation of the syndrome. The clinical and histologic findings described herein may be relatively common among AIDS patients and are quite different from those of classic disseminated histoplasmosis.

Treatment of malignant carcinoid syndrome with a long-acting somatostatin analogue.

A patient with malignant carcinoid syndrome was treated with a long-acting somatostatin analogue. The cutaneous and systemic improvement our patient had while receiving this therapy is described.

Nonmelanized macromelanosomes in a cellular blue nevus. Light and electron microscopic observations.

We noted nonmelanized and partially melanized macromelanosomes in a cellular blue nevus and studied their light microscopic and ultrastructural features. Numerous intracytoplasmic eosinophilic inclusions were found in the lesion; individual cells contained up to nine, although most cells demonstrated two or three. The "macromelanosomelike" inclusions ranged in size from 1 to 15 microns. Most of them were partially melanized, and some were nonmelanized. These globules were periodic acid-Schiff positive and diastase resistant, with a centrally melanized core, best seen with the Fontana-Masson technique. S100 protein stained positively the cytoplasm of some nevus cells but not the inclusions. Electron microscopy confirmed the centrifugal melanization of these structures and their targetlike morphologic characteristics. Nine other cellular blue nevi from our files failed to show similar intracytoplasmic inclusions.

Detection of human papillomavirus in nongenital Bowen's disease by in situ DNA hybridization.

Genital Bowen's disease has been strongly linked in recent studies to human papillomavirus (HPV). Nongenital Bowen's disease has been less well investigated, although isolated reports, all of which involved detection of HPV after extraction of DNA from fresh-frozen tissue, have been made. We investigated 25 cases of nongenital Bowen's disease in 5 black and 20 white patients for the presence of HPV types 1, 6, 11, 16, and 18 using paraffin-embedded tissues. Human papillomavirus was present in six specimens from 3 of the 5 black patients (one previously reported to be positive on Southern blot) and 3 of the 20 white patients; HPV 16 was detected in all 6 cases on low-stringency testing, but only 4 remained positive on high-stringency testing. This suggests an HPV closely related to but not entirely homologous with HPV 16 in the 2 remaining cases. Five of the 6 positive specimens were lesions from the hands and feet and 1 was from the volar aspect of the arm. Clinical factors associated with the presence of HPV included black race, location on the palmar surface and the feet, young age, and verrucous or hyperkeratotic clinical appearance. Of the 6 positive cases, all 5 of the patients available for examination also had evidence of HPV-associated genital lesions. No specific histopathologic features were found to be indicative of the presence or absence of HPV.

Systemic lupus erythematosus occurring in a patient with epidermolysis bullosa acquisita.

A dystrophic bullous eruption that met all the criteria for epidermolysis bullosa acquisita (EBA) developed in a 19-year-old woman five years before the onset of clinical and serologic evidence of systemic lupus erythematosus (SLE). Electron microscopic studies of skin lesions both before and after the development of SLE were consistent with the previously reported electron microscopic findings in patients with EBA. Direct immunofluorescence microscopic studies done on bullae before and after the diagnosis of SLE showed linear depositions of immunoglobulin and complement; indirect immunofluorescence microscopic study findings consistently showed no abnormalities. These findings have been noted in other cases of EBA and may implicate autoimmune, immunologic factors in the pathogenesis of the disease process. To our knowledge, the finding of SLE in association with EBA has not been previously reported.

Bowen's disease of the feet. Presence of human papillomavirus 16 DNA in tumor tissue.

A 36-year-old black man with bilateral squamous cell carcinoma in situ of the feet is described. The DNA hybridization analysis performed on the tumor tissue demonstrated the presence of human papillomavirus 16 DNA. Human papillomavirus 16 has been detected repeatedly in genital carcinomas, and evidence is mounting that it may play an important role in the development of malignancy.

Simultaneously active lesions of vitiligo and erythema dyschromicum perstans.

Recently, a patient presented to us with skin that had areas of normal pigmentation, hyperpigmentation, and depigmentation. Workup eventually showed him to have simultaneously active lesions of a depigmenting disorder, vitiligo, and a hyperpigmenting disorder, erythema dyschromicum perstans.

Vesicular Jarisch-Herxheimer reaction.

The Jarisch-Herxheimer reaction is a self-limited, febrile episode that may occur following antibiotic therapy for syphilis. We report four cases of a heretofore unrecognized vesicular variant of the Jarisch-Herxheimer reaction. It is important to distinguish this phenomenon from an allergic drug eruption.

Chromomycosis. The association of fungal elements and wood splinters.

In two separate specimens received for histopathologic examination, pigmented fungal elements were found within or on embedded wood splinters associated with a foreign-body reaction. The fungus was found to be in direct contact with the surrounding dermis. These findings support the concept of inoculation as a pathogenetic mechanism in cutaneous chromomycosis.

Pachyonychia congenita. Electron microscopic and epidermal glycoprotein assessment before and during isotretinoin treatment.

Two patients, a father and son, with pachyonychia congenita were treated with orally administered isotretinoin because the extreme deformity and discomfort associated with their massive keratoderma interfered with their work and school, respectively. While clinical benefits could not be sustained, electron microscopic findings compatible with suppression of abnormal keratinization were observed. In addition, skin biopsy samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the gels were then subjected to a lectin overlay technique with concanavalin A labeled with iodine 125. The distribution of specific glycoproteins was found to be different for lesional as against normal epidermis. The procedure was repeated after oral treatment with isotretinoin. The labeled glycoprotein pattern of the lesional epidermis was clearly distinguishable from both the pretreatment lesional and the normal epidermis; it was mostly intermediate between the two. The normal epidermis was virtually unaffected by the retinoid treatment.

Effect of dietary omega-3 and omega-6 fatty acid sources on PUVA-induced cutaneous toxicity and tumorigenesis in the hairless mouse.

Because of concern about psoralen-induced phototoxicity and photocarcinogenesis, we investigated the effects of dietary lipids in a mouse model in which 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy has been shown to be carcinogenic. SKH-Hr-1 hairless albino mice were fed diets containing either omega-3 or omega-6 fatty-acid sources (menhaden oil and corn oil, respectively). After 2 weeks on the diets, the mice were treated topically with 8-MOP and then exposed to UVA (5 J/cm2). Mice receiving the omega-3 fatty-acid source exhibited a marked decrease in inflammatory response and a more rapid repair, as expressed both grossly and microscopically. In support of the latter response, i.e. repair, ornithine decarboxylase activity was about 20% greater in animals receiving the omega-3 fatty-acid source. The effects of the dietary fatty acid sources on PUVA tumorigenesis were examined in long-term studies in which animals were treated topically with 0.01% 8-MOP thrice weekly after which they were exposed to UVA (1 J/cm2). These studies indicated that a dietary lipid rich in omega-3 fatty acid and known to exhibit anti-inflammatory properties can markedly ameliorate the course of PUVA toxicity but does not impede the course of PUVA tumorigenesis.

Cutaneous manifestations of dysproteinemias.

A number of cutaneous lesions may represent signs of underlying dysproteinemia. The lesions may result from direct infiltration by plasmacytes and immunoblasts--such as plasmacytomas seen with multiple myeloma--or they may result from indirect effects of the immunoglobulins by a number of different mechanisms. Because the spectrum of cutaneous lesions is so large and at times nonspecific, it is important to keep dysproteinemia in one's differential diagnosis at all times. Careful monitoring of these patients is important since the latency period for the actual development of a plasma cell malignancy may be years.

Eyelid pigment implantation: early and late histopathology.

Full-thickness sections of upper and lower eyelids were obtained from patients who had eyelid pigment implantation performed by one surgeon. These four patients represented eyelid pigment implantation at varying postoperative stages ranging from 6 months to 4 years. Light microscopic evaluation revealed pigment within dermis and superficial orbicularis muscle. Light and electron microscopic evaluation revealed the vast majority of the pigment to be located intracellularly, primarily within macrophages. No foreign-body reaction was seen around the implanted material. Electron probe analysis of the pigment showed only the presence of iron. Analysis of the unused pigment revealed small amounts of silica and magnesium. These substances could not be identified by electron probe analysis in the eyelid tissues.

Disciform erythrasma.

A case of disciform erythrasma is presented. This unusual manifestation of a common cutaneous infection may mimic other dermatologic disorders, including lichen sclerosus et atrophicus and plaque-type parapsoriasis. The condition is characterized by an atrophic appearing surface, located in nonintertriginous areas. Appropriate diagnostic procedures easily differentiate disciform erythrasma. These include Wood's light examination, potassium hydroxide preparation, and skin scrapings or tissue sections stained with Gram stain, periodic acid-Schiff, Giemsa, or methylene blue.

Renal cell carcinoma metastatic to skin.

A case of renal cell carcinoma metastatic to the skin is reported. Renal cell carcinoma is a relatively uncommon malignancy that frequently metastasizes to the skin.

Malignant histiocytosis.

Malignant histiocytosis, also known as histiocytic medullary reticulosis, is a rare neoplasm of malignant histiocytes. Clinical findings include fever, weight loss, hepatosplenomegaly, lymphadenopathy, anemia, thrombocytopenia, and a rapidly worsening course. Approximately 7 percent of patients have skin manifestations early in the course of their disease. In these patients, diagnosis based on examination of a skin biopsy specimen may be crucial. A case of malignant histiocytosis is presented in which the diagnosis was first suggested by findings on the skin biopsy specimen.

Atypical mycobacterial infection in a patient with hairy cell leukemia.

A case of a cutaneous tumor caused by atypical mycobacterial infection (Mycobacterium kansasii) in a patient with hairy cell leukemia is reported. Surgical removal of the lesion and subsequent combination antituberculotic treatment led to a cure of this infection. Remission of the leukemia was achieved with interferon alfa.

Giant molluscum contagiosum of the sole.

Molluscum contagiosum is usually diagnosed on the basis of clinical findings. However, when this common lesion is present in an unusual location, such as the sole of the foot, diagnosis may be more difficult. The following case demonstrates that molluscum contagiosum infection should be considered in the differential diagnosis of lesions of the soles.