Low-dose prednisolone ameliorates acute renal failure caused by cholesterol crystal embolism.

AIMS: The prognosis of renal cholesterol crystal embolism (CCE) is poor. Although various treatments for CCE have been attempted, there is no optimal therapy. We tested the effect of low-dose prednisolone (PS) on CCE-related acute renal failure (ARF). PATIENTS AND METHODS: 7 patients (mean age 69 years) diagnosed with CCE-related ARF were treated with oral PS at 15-20 mg/day for 2-4 weeks, which was then tapered at 5 mg/day over 2-4 weeks, followed by 5 mg/day maintenance dose. Recurrent ARF during PS tapering was treated with a larger dose of PS. RESULTS: Inciting factors were identified in four patients: coronary angiography (n=3) and cerebral angiography (n=1). On admission, serum creatinine (SCr) was 2.1 +/- 0.3 mg/dl (mean +/- SEM). SCr and eosinophil count before treatment were 4.2 +/- 0.4 mg/dl and 682 +/- 73/microl, respectively. PS therapy improved ARF in all cases at week 2 (SCr 3.8 +/- 0.5 mg/dl) parallel to a decrease in eosinophilia (116 +/- 30/microl), and at week 4 (3.1 +/- 0.4 mg/dl and 134 +/- 20/microl, respectively). At last follow-up, renal function was improved or maintained in 5 patients compared with that at week 4 post-treatment. One patient died of lung cancer. Another required LDL apheresis and hemodialysis but died due to CCE-related multi-organ failure. A third patient had recurrent ARF and was re-treated with a larger dose of PS, which resulted in an immediate decrease in SCr. However, the patient developed acute renal dysfunction due to congestive heart failure, and required hemodialysis. CONCLUSIONS: Low-dose PS improved CCE-related ARF, probably through amelioration of inflammatory reaction surrounding affected renal vessels.

Analytical method to examine the effects of carbon dioxide lasers on skin: a study using wrinkles induced in hairless mice.

BACKGROUND AND OBJECTIVE: Investigation of the wrinkle smoothing process elicited by CO(2) laser treatment is important for understanding the mechanism involved in their repair. STUDY DESIGN/MATERIALS AND METHODS: Hairless mice with wrinkles induced in their dorsal skin by long-term exposure to ultraviolet radiation in the wavelength range of 290-320 nm were treated with a CO(2) laser. By using this model, we investigated the external appearance, histologic changes, and the mechanical properties of the skin during the wrinkle repair. RESULTS: Laser treatment with an appropriate intensity caused wrinkles to smooth completely. In the healing process, reepithelialization and collagen tissue regeneration in the upper dermis was observed. However, marked changes in the skin were noted, such as increases in the collagen layer and in the skin thickness, and changes in the mechanical properties of the skin, despite the favorable external appearance. CONCLUSIONS: An abnormal state characterized by excessive collagen regeneration and other changes in the dermis occur concomitantly with wrinkle smoothing.

Malignant melanoma cells in the eccrine apparatus.

A case of malignant melanoma arising on the sole of a 75-year-old Japanese man is presented. Histopathologically, in addition to the intraepidermal and intradermal malignant melanoma cells reaching the upper part of the dermis, cells were also found in the deep part of the ductal epithelium of the eccrine apparatus. Melanoma cells, and melanocytic nevus cells as well, are rarely found within the epithelial structure of sweat glands, yet they are frequently found in that of hair follicles. In order to avoid a residue of melanoma cells in the deep part of the eccrine apparatus, a fairly deep excision should be performed even for this melanoma.

Carbon dioxide laser treatment promotes repair of the three-dimensional network of elastic fibres in rat skin.

BACKGROUND: We have previously reported that ultraviolet (UV) B irradiation induces a loss of linearity in the three-dimensional structure of dermal elastic fibres, which results in the reduction of elastic properties of the skin and leads to wrinkle formation. We further reported that repair of wrinkles by all-trans retinoic acid is accompanied by recovery of the linearity of elastic fibres. Carbon dioxide (CO2) lasers are widely used for treating wrinkles in cosmetic surgery. OBJECTIVES: To perform CO2 laser treatment of wrinkles induced in rat skin by UVB irradiation and to evaluate changes in the three-dimensional structure of dermal elastic fibres during wrinkle repair. METHODS: Wrinkles were induced in the hind limb skin of Sprague-Dawley rats by UVB irradiation (130 mJ cm-2 three times weekly for 6 weeks), followed by CO2 laser treatment (11.3 J cm-2). The surface appearance of the skin was evaluated by replica observation 6 and 10 weeks after CO2 laser treatment followed by measurement of mechanical properties using a Cutometer. Subsequently, perfusion fixation and digestion with formic acid were performed and elastic fibres were observed by scanning electron microscopy (SEM). Image analysis of SEM micrographs was carried out to evaluate the linearity in the three-dimensional structure of elastic fibres. RESULTS: Six weeks after CO2 laser treatment, all parameters of skin mechanical properties in the UVB-irradiated group recovered to levels of the control non-irradiated group, accompanied by repair of wrinkles and a significant increase in linearity of the three-dimensional structure of elastic fibres. CONCLUSIONS: These findings indicate that CO2 laser treatment has a therapeutic potential to repair wrinkles to non-irradiated levels through recovery of the three-dimensional structure of elastic fibres.

Multiple palisading granulomas in the scalp of an infant: a case report.

BACKGROUND: We describe an unusual lesion that represents an uncommon but important element in the differential diagnosis of subcutaneous scalp nodules in a child. CASE DESCRIPTION: A 1-year-old boy presented with two clusters of subcutaneous scalp nodules. The lesions increased in size and number. Computed tomography showed no changes in underlying bone. Findings on magnetic resonance imaging were nonspecific. Serologic and clinical evaluation showed no evidence of rheumatic disease. Complete excision of the nodules, together with adjacent fascia and galea, was performed. Histopathologic examination showed the lesions to be palisading granulomas; given the absence of rheumatic disease, these represented deep granuloma annulare, a benign condition. No recurrence has been observed in our patient. CONCLUSION: While we chose total excision because of preoperative concerns about a possible malignant tumor, some other authors have suggested that surgery be limited to confirmatory biopsy when a benign lesion such as palisading granuloma is strongly suspected.

Response of naevus of Ota to Q-switched ruby laser treatment according to lesion colour.

Lesions of naevus of Ota range in colour from light brown to blue, and even greenish-black. To develop guidelines for optimal treatment, we evaluated the number of Q-switched ruby laser treatments required to eliminate the pigmentation of such lesions classified by colour. Over a period of 6 years, we evaluated 151 Japanese patients with naevus of Ota who had been treated with the Q-switched ruby laser at a low energy level (wavelength 694.3 nm; pulse duration 28 x 10-9 s; energy fluence 5 J/cm2; spot size 6.5 mm) every 2 months. Each lesion was classified by colour as brown (n = 22), brown-violet (n = 42), violet-blue (n = 81) and blue-green (n = 6). The 22 predominantly brown lesions attained an excellent (100-95%) or good (95-75%) cosmetic result following three laser treatments in all patients who received this number of treatments. In the 42 brown-violet lesions, 25 of the 29 good or excellent results were achieved after four treatments; the 13 less successful results were in patients who had one to three treatments. In the 81 violet-blue lesions, 54 of the 65 good or excellent results were achieved after four treatments and 64 of 65 after five treatments, whereas all 16 less good results were in patients who had only one to three treatments. However, in the six blue-green lesions, six or more treatments were required to achieve a similarly favourable result. At the end of treatment, the area was virtually free of scarring, and its texture resembled that of the surrounding normal skin. We have confirmed that the use of the Q-switched ruby laser at a low energy level can eliminate the pigmentation of naevus of Ota. While the desired improvement can be obtained within 1 year, the number of treatments appears to depend on the predominant colour of the lesion.

Molecular cloning, sequencing, and expression of the gene encoding alkaline ceramidase from Pseudomonas aeruginosa. Cloning of a ceramidase homologue from Mycobacterium tuberculosis.

We previously reported the purification and characterization of a novel type of alkaline ceramidase from Pseudomonas aeruginosa strain AN17 (Okino, N., Tani, M., Imayama, S., and Ito, M. (1998) J. Biol. Chem. 273, 14368-14373). Here, we report the molecular cloning, sequencing, and expression of the gene encoding the ceramidase of this strain. Specific oligonucleotide primers were synthesized using the peptide sequences of the purified ceramidase obtained by digestion with lysylendopeptidase and used for polymerase chain reaction. DNA fragments thus amplified were used as probes to clone the gene encoding the ceramidase from a genomic library of strain AN17. The open reading frame of 2,010 nucleotides encoded a polypeptide of 670 amino acids including a signal sequence of 24 residues, 64 residues of which matched the amino acid sequence determined for the purified enzyme. The molecular weight of the mature enzyme was estimated to be 70,767 from the deduced amino acid sequence. Expression of the ceramidase gene in Escherichia coli, resulted in production of a soluble enzyme with the identical N-terminal amino acid sequence. Recombinant ceramidase was purified to homogeneity from the lysate of E. coli cells and confirmed to be identical to the Pseudomonas enzyme in its specificity and other enzymatic properties. No significant sequence similarities were found in other known functional proteins including human acid ceramidase. However, we found a sequence homologous to the ceramidase in hypothetical proteins encoded in Mycobacterium tuberculosis, Dictyostelium discoideum, and Arabidopsis thaliana. The homologue of the ceramidase gene was thus cloned from an M. tuberculosis cosmid and expressed in E. coli, and the gene was demonstrated to encode an alkaline ceramidase. This is the first report for the cloning of an alkaline ceramidase.

Long- and short-term histological observations of congenital nevi treated with the normal-mode ruby laser.

OBJECTIVE: To evaluate histologically the long- and short-term changes associated with cosmetic improvement or failure of normal-mode ruby laser treatment of patients with congenital nevi. DESIGN: A biopsy of the laser-treated lesions of 10 patients with good or poor cosmetic results was performed at periods up to 8 years 10 months after treatment (mean, 4 years 9 months). Short-term findings were evaluated in 3 patients. SETTING: Ueda Setsuko Clinic and the Dermatology Unit of the Kyushu University, Fukuoka, Japan. PATIENTS: Of the 85 Japanese patients with relatively large congenital nevi who had been treated with the normal-mode ruby laser since 1990, 13 gave informed consent for biopsy and histological examination of the treated area. RESULTS: A long-term follow-up study of the 8 patients with good cosmetic results showed the presence of residual nevus cells 1.11 +/- 0.35 mm (mean +/- SD) (range, 0.63-2.05 mm) below the skin surface. Above these cells was a layer of connective tissue that formed a subtle microscopic scar that preserved the normal structure of the papillary dermis. Hair follicles were damaged at the base, and the hairs were attenuated. However, in the 2 patients with poor cosmetic results, nests of pigmented cells were commonly seen in the epidermis, and melanin was relatively abundant in basal keratinocytes. No malignant changes were observed in any patient. A short-term study in 3 patients showed damage to pigmented cells in the epidermis and upper dermis as observed following electrodesiccation. CONCLUSIONS: Multiple treatments with the normal-mode ruby laser produced immediate thermal damage to the superficial nests of nevus cells and a subsequent remodeling of the superficial connective tissue. When the thickness of the subtle microscopic scar reached 1 mm, it masked the underlying residual nevus cells and achieved a good cosmetic result. Follow-up for at least 8 years after laser treatment showed no evidence of malignant change in the treated areas.

On rugged shape of skin tumor (basal cell carcinoma).

Basal cell carcinoma (BCC) is the most common cancer of the skin that is made of transformed basal cells of the human epidermis, and spreads along the epidermis--dermis junction. It often forms tumor cell mass that protrudes towards the dermal connective tissue with many branches. Histopathological examination of the cancer demonstrates the cell mass of a rugged shape appearing as many regular spaced islands in a two-dimensional section. We study the process of cell proliferation and spatial pattern formation of the skin tumor by a pair of partial differential equations of tumor cells and nutrients. The assumptions are: (1) proliferation rate of tumor cells depends on the availability of nutrients, which simply diffuse out of capillaries through connective tissue; (2) nutrients are consumed by active tumor cells; (3) cell diffusion coefficient expressing tumor cell movements increase with the cell density and the nutrient availability. Starting from the initial condition with a single layer of tumor cells. the model develops a smooth colony if n'0 is large, but a characteristic rugged spatial pattern of tumor cell mass if n'0 is small, in which n'0 is nutrient concentration multiplied by square root of growth efficiency divided by diffusion coefficient of nutrients. The proportion of the area occupied by tumor cells increases with n'0. The coefficient of variation in the width of "islands" of tumor cell mass is rather small (0.2 reverse similar0.6), implying the regularity of the spatial pattern. We also analyses the photographs of a two-dimensional section of tumor cell mass and compare the spatial patterns generated by the model.

The proliferative properties of tumor cells differentially correlate with the host immune responses in anogenital Bowen's disease.

Bowen's disease is a squamous cell carcinoma in situ that rarely invades into the underlying dermis. In order to evaluate the relationship between the cytological properties of the tumor cells and the host immune response, we have examined the expression of p53 and proliferating cell nuclear antigen (PCNA), and the number of mitotic cells, clumping cells, koilocytes, Langerhans cells (LCs) and dermal lymphoid cell infiltration in 18 cases of anogenital Bowen's disease. When compared with normal anogenital skins (n = 10), a statistically significant number of p53-positive cells, PCNA-positive cells, mitotic cells, clumping cells, koilocytes and dermal lymphoid cells was observed in the cases of Bowen's disease. Importantly, there existed a very strong correlation between the number of PCNA-positive tumor cells and the number of infiltrated dermal lymphoid cells. Moreover, the number of mitotic cells significantly correlated with the number of intratumoral LCs. The in situ hybridization technique for human papilloma virus (HPV) demonstrated that the HPV-infected Bowen's disease showed a similar histological and immunohistological pattern as the HPV-non-infected counterparts, except for increased koilocyte formation and decreased p53 positivity. The present data suggest that the proliferative activity of Bowen's disease significantly correlates with the host immune reaction, and that the host immune system may differentially recognize the different cytological properties of tumor cells in the Bowen's disease.

Normal-mode ruby laser for treating congenital nevi.

BACKGROUND: Q-switched laser therapy is known to be highly effective in treating dermal melanocytosis and pigmented epidermal lesions. However, to our knowledge, there are no reports on the effectiveness of laser therapy for congenital nevi. We evaluated the clinical efficacy and side effects of normal-mode ruby laser therapy for congenital pigmented lesions containing abundant melanin. OBSERVATIONS: A normal-mode ruby laser (pulse duration, 0.3-1.0 x 10(-3) seconds; energy fluence, 10-30 J/cm2; and spot size, 10 x 10 or 15 x 15 mm) (Toshiba Corp, Tokyo, Japan) was used to treat 3 patients with congenital nevi at intervals of 1 to 4 months. In all 3 cases, the pigmented lesions were significantly reduced almost to the level of the surrounding normal skin after 4 laser treatments. The treated areas were virtually free of scarring, and the skin texture resembled that of the surrounding normal skin. Unsightly hair growth was also reduced. CONCLUSIONS: The normal-mode ruby laser was effective in treating congenital nevi and produced good cosmetic results. The risk of recurrence is unknown, but the 3 patients in our study did not have any recurrences during the 18- to 39-month study period.

Leser-Trélat sign with anaplastic ependymoma--an autopsy case.

A 36-year-old Japanese male, who 7 years previously had been diagnosed as having an ependymoma in the left parietal region, had received surgery, chemotherapy and radiotherapy. He later developed a rapid growth of multiple skin lesions on his back and extremities, which coincided with a regrowth of the tumor. Postmortem examination revealed that the ependymoma showed anaplastic transformation and necrosis; however, no malignancy was observed in the extracranial organs. The skin lesions were histologically diagnosed as seborrheic keratoses. We have, therefore, diagnosed the patient as having Leser-Trélat sign associated with anaplastic ependymoma.

Presence of elevated carcinoembryonic antigen on absorbent disks applied to nipple area of breast carcinoma patients.

BACKGROUND: Carcinoembryonic antigen (CEA) is used as a serum marker to detect and monitor the status of various kinds of malignant tumors. To determine whether CEA might be detected in secretions collected topically from around the nipple area, and whether its secretion might differ in a cancerous versus a noncancerous breast, we developed a simple method for collecting and measuring CEA, using a small cellulose membrane disk and an enzyme immunoassay. METHODS: We measured the amount of CEA excreted from the nipple area of 22 healthy control women and 32 women with unilateral breast carcinoma confirmed histologically. Secretions were collected from the nipple area by affixing a small (20 mm diameter) absorbent disk made of nitrocellulose membrane backed with filter paper to that area for 24 hours. Substances absorbed by the membrane were then subjected to an immunoassay for CEA using anti-CEA antibodies. RESULTS: In the 22 healthy subjects, a small amount of CEA (0.6 +/- 0.9 units) was secreted from each nipple, which was equally low regardless of the phase of the menstrual cycle. In contrast, 30 of the 32 women with breast carcinoma secreted significantly greater amounts of CEA from the cancerous (16.1 +/- 8.2) than the noncancerous (2.0 +/- 2.2) breast. Such a difference (14.1 +/- 8.0) in CEA excretion was not observed in the healthy controls (0 +/- 0). CONCLUSIONS: These findings suggest that such disks may provide a simple and noninvasive method of collecting trace molecules, including CEA, in skin secretions around the nipple to evaluate functional disorders of the mammary glands, particularly breast carcinoma. Additional studies are indicated in larger groups of women with various stages of breast carcinoma as well as with benign breast diseases.

Angiocentric immunoproliferative lesions of the skin show lobular panniculitis and are mainly disorders of large granular lymphocytes.

Eleven patients with angiocentric immunoproliferative lesion (AIL) of the skin were studied. Histologically, three patients were grouped into AIL grade II (AIL-II), whereas eight showed angiocentric lymphoma (AIL-III). All the patients' specimens exhibited lobular panniculitis. Infiltrating atypical lymphocytes in nine patients possessed electron-dense membrane bound granules in electron microscopy. Phenotypically, the lymphoid cells in the AIL-II patients were positive for CD3 epsilon; two of these showed a positive reaction to CD2, CD7, and CD8, but lacked natural killer-associated (NKa) antigens CD16, CD56, and CD57. In six AIL-III patients, lymphoma cells were positive for CD2 in all patients, CD56 in five, CD3 epsilon in four, CD7 in four, interleukin-2 beta receptor in four, a pore-forming protein in four, and CD30 in three patients. The remaining two AIL-III patients had B-cell lymphoma. By the Southern blot analysis, three patients with AIL-III showed a rearranged T-cell-receptor beta-gene or a deletion of its germline. The preceding results in nine of 11 patients suggest that abnormal or neoplastic large granular lymphocytes with the characteristics of T and NK cells have an important role in producing the angiocentric/angiodestructive features and lobular panniculitis. Clinically, all three patients with AIL-II and four with AIL-III showed liver dysfunction, cytopenia, and abnormal coagulopathy during the clinical course. Five patients with AIL-III died within 8 months. The histological grading of AIL, patients' age, and limited clinical stage of the disease seem to correlate with response to the treatment and prognosis.

Increased serum level of interleukin-6 in patients with psoriatic arthritis and thrombocytosis.

The role of elevations of serum cytokines in psoriasis is a provocative issue. We report two patients with psoriasis who had episodes of fever, arthritis, and general fatigue. Their symptoms seemed to be associated with increases in serum levels of interleukin (IL)-6, which paralleled the severity of clinical symptoms as well as elevated serum titers of C-reactive protein (CRP) and platelet counts. Since IL-6 is a multipotential cytokine with B-cell activating, T-cell activating, and thrombocytopoietic functions, the symptoms and abnormal laboratory findings in these patients may have been related to their increased serum levels of IL-6. Monitoring the serum level of this cytokine may thus be useful in evaluating the clinical status of patients with psoriatic arthritis.

Differential cell surface distribution of adhesion molecules demonstrated by immuno-scanning electron microscopy.

Scanning electron microscopy with immuno-gold labeling revealed that epidermal keratinocytes expressed ICAM-1 and HLA-DR molecules on their surfaces in patterns that differed in mycosis fungoides (MF) and lichenoid reaction (LR). ICAM-1 molecules, visualized as deposits of gold particles, were present as clusters adjacent to the junctions interconnecting the keratinocytes of MF lesions. LFA-1 molecules were seen as granules on the surfaces of all infiltrates, most of which also expressed ICAM-1. HLA-DR molecules were seen continuously along the borders of the individual keratinocytes. In LR, ICAM-1 and HLA-DR were expressed only sparsely on the undersurface of the epidermis, whereas the infiltrates expressed LFA-1 molecules on their surfaces. These findings may explain the differing histological features of MF and LR: ICAM-1 molecules present on the intercellular junctions of MF epidermis lead the LFA-1-bearing cells to migrate into the interspaces of the keratinocytes, thus producing "epidermotropism". These cells aggregate by means of co-expressed ICAM-1 to thus produce the appearance of a "microabscess". In LR, on the other hand, the minimal expression of ICAM-1 on the epidermal undersurface leaves most infiltrates within the dermis, thus producing a "band-like infiltrate" beneath the epidermis.

Deposition of basic fibroblast growth factor on surface of epidermal melanocytes suggesting the stromal control of epidermal pigmentation.

Scanning electron microscopy with immunogold labeling was used to demonstrate the in vivo distribution of molecules of basic fibroblast growth factor (bFGF) that were expressed and/or present on the surface of the cells of the normal epidermis and dermal connective tissue of humans. We found that molecules of bFGF, seen as deposits of gold particles, were present densely on the surfaces of the melanocytes but not the epidermal keratinocytes. In connective tissue, these molecules were present exclusively on the surfaces of the fibroblasts, macrophages, vascular endothelial cells, and the basement membrane surrounding the endothelial tube. The selective deposition of bFGF molecules on the melanocytes suggests that the dermal connective tissue may be involved in controlling the proliferation of melanocytes by means of bFGF molecules in vivo, since these melanocytes require bFGF to proliferate in vitro. The latter is synthesized and stored exclusively in the connective tissue.