Chronic actinic dermatitis developed during phototherapy for psoriasis.

A patient with psoriasis vulgaris had been successfully treated with PUVA and UVB therapy. During maintenance phototherapy, he suddenly became photosensitive and developed eczematous eruption. Minimal response doses to UVB and UVA were extremely low--1.09 mJ/cm2 and 0.3 J/cm2, respectively. No chemical substances were identified as the responsible photosensitizer. The condition was diagnosed as chronic actinic dermatitis (CAD). PUVA therapy was unsatisfactory because it was not possible to administer an adequate dose of UVA. Oral cyclosporine, topical corticosteroid and sunscreen were used with beneficial therapeutic effects on psoriasis and CAD. As far as we know, the development of CAD during phototherapy has not been previously reported.

Intra-abdominal desmoplastic small round cell tumor (IDSRT).

Intra-abdominal desmoplastic small round cell tumor (IDSRT) is a rare neoplasm that develops in the abdominal cavity in young people. We experienced a 27-year-old man who visited with ascites of unknown cause. Compression of the colon was found by barium enema examination. On colonoscopic examination, diffuse white elevated lesions, about 5 mm in diameter, surrounded by rubedo, so-called aphthoid lesions, were also observed. IDSRT was diagnosed by biopsy at laparotomy, and chemotherapy with cyclophosphamide, etoposide, doxorubicin, and cisplatin was performed. The tumors shrank temporarily (partial response), but subsequently grew in size again. The patient died during the second course of chemotherapy after relapse. We present one case report, together with a review of the literature.

Structures, enzymatic properties, and expression of novel human and mouse secretory phospholipase A(2)s.

Mammalian secretory phospholipase A(2)s (sPLA(2)s) form a family of structurally related enzymes that are involved in a variety of physiological and pathological processes via the release of arachidonic acid from membrane phospholipids or the binding to specific membrane receptors. Here, we report the cloning and characterization of a novel sPLA(2) that is the sixth isoform of the sPLA(2) family found in humans. The novel human mature sPLA(2) consists of 123 amino acids (M(r) = 14,000) and is most similar to group IIA sPLA(2) (sPLA(2)-IIA) with respect to the number and positions of cysteine residues as well as overall identity (51%). Therefore, this novel sPLA(2) should be categorized into group II and called group IIE (sPLA(2)-IIE) following the recently identified group IID sPLA(2) (sPLA(2)-IID). The enzymatic properties of recombinant human sPLA(2)-IIE were almost identical to those of sPLA(2)-IIA and IID in terms of Ca(2+) requirement, optimal pH, substrate specificity, as well as high susceptibility to the sPLA(2) inhibitor indoxam. Along with the biochemical properties of proteins, genetic and evolutional similarities were also observed among these three types of group II sPLA(2)s as to the chromosomal location of the human gene (1p36) and the exon/intron organization. The expression of sPLA(2)-IIE transcripts in humans was restricted to the brain, heart, lung, and placenta in contrast to broad expression profiles for sPLA(2)-IIA and -IID. In sPLA(2)-IIA-deficient mice, the expression of sPLA(2)-IIE was markedly enhanced in the lung and small intestine upon endotoxin challenge, which contrasted with the reduced expression of sPLA(2)-IID mRNA. In situ hybridization analysis revealed elevation of sPLA(2)-IIE mRNA at alveolar macrophage-like cells in the lung of endotoxin-treated mice. These findings suggest a distinct functional role of novel sPLA(2)-IIE in the progression of inflammatory processes.

A retinoic acid-inducible modular protease in budding ascidians.

Retinoic acid-treated mesenchyme cells of the budding ascidian Polyandrocarpa misakiensis acquire an organizer activity to induce a secondary body axis when implanted into developing buds. We identified several different mRNAs that were upregulated in the mesenchyme cells after retinoic acid treatment. We isolated a cDNA clone corresponding to one of these mRNAs. The C-terminal region of the predicted protein product is homologous to the catalytic domain of serine proteases that belong to the trypsin family. The N-terminal region contains several types of protein-protein interaction domains. We therefore named this protein tunicate retinoic acid-inducible modular protease (TRAMP). Expression of the TRAMP mRNA in mesenchyme cells during budding and its upregulation by retinoic acid were demonstrated by reverse transcription-PCR and in situ hybridization. A glutathione S-transferase-TRAMP fusion protein showed a protease activity with trypsin-like substrate specificity and stimulated proliferation of the cell line established in this species.

Cell-killing efficiency and number of platinum atoms binding to DNA, RNA, and protein molecules of HeLa cells treated with combinations of hyperthermia and cis-diamine(glycolato)platinum(II).

HeLa S-3 cells were treated with 195mPt-radiolabeled cis-diamine(glylato)platinum(II) (254-S) for 60 min at various temperatures, and the relationship between the lethal effect and the number of Pt atoms binding to DNA, RNA, and proteins was examined. The mean lethal concentration (D0) of 254-S for a 60-min treatment at 0 degree C, 25 degrees C, 37 degrees C, 40 degrees C, 42 degrees C, and 44 degrees C was 233, 132, 61.1, 42.7, 25.6, and 9.9 microM, respectively. By using identically treated cells, the numbers of Pt atoms combined with DNA, RNA, and protein molecules were determined in the subcellular fractions. Thus, the D0 values given as drug concentrations were replaced with the number of Pt atoms combined in each fraction. The, the cell-killing efficiency of the Pt atom was expressed as the reciprocal of the number of Pt atoms combined and was calculated for each molecule. The efficiency for the DNA molecule was 0.61 x 10(4), 1.09 x 10(4), 1.88 x 10(4), 1.90 x 10(4), 2.66 x 10(4), and 5.88 x 10(4) nucleotides, respectively, for the conditions described. From 0 degree C to 44 degrees C, the cell-killing efficiency of Pt atoms increased by a factor of 9.6.

UCE6, a new antitumor antibiotic with topoisomerase I-mediated DNA cleavage activity produced by actinomycetes: producing organism, fermentation, isolation and biological activity.

A novel antitumor antibiotic, UCE6 (1,3,8,10,11-pentahydroxy-2-methyl-10-(2-oxo-4-hydroxypentyl)na phthacene-5, 12-dione) with topoisomerase I-mediated DNA cleavage activity, was isolated from the culture broth of actinomycetes strain UOE6. Addition of silicone oil antifoam agent, KS69 (2%), to the fermentation enhanced the production of UCE6 by approximately 3 fold. A total of 1.15 g of UCE6 was recovered as reddish orange crystals from a 100 liter fermentation supplemented with 2% KS69. UCE6 exhibited growth inhibitory activity against HeLa S3, HCT116 and Lu-65 cells comparable to that of camptothecin.

Inhibitors of DNA topoisomerase I and II isolated from the Coptis rhizomes.

A water extract of Coptis chinensis was found to have the ability to stabilize the cleavable complex with mammalian DNA topoisomerase I. As the result of bioassay-guided fractionation, two protoberberine alkaloids, epiberberine and groenlandicine, were identified as active principles with topoisomerase I-mediated DNA cleavage activity in vitro. These two alkaloids did not induce topoisomerase II-mediated DNA cleavage. During further examination of the structurally related protoberberine alkaloids, berberrubine which is produced during the processing of Coptis rhizome as traditional medicine, was identified as a specific inducer of topoisomerase II-mediated DNA cleavage in vitro. These results indicated that protoberberine alkaloids are a chemical family which can induce cleavable complexes with topoisomerases I and II.

Effects of sensory stimulation on respiratory cardiac cycle variability in humans.

The effects of the phase of respiration on the response of respiratory cardiac cycle variability to sensory stimulation were studied in five healthy young male subjects. Transcutaneous electrical stimulation of the ulnar nerve or hand-grip exercise was applied during inspiration or expiration. Although both electrical stimulation and hand-grip exercise depressed respiratory cardiac cycle variability, the nature of the depression differed according to where in the respiration cycle the stimuli were applied. The amplitude of respiratory cardiac cycle variation was significantly decreased when either stimulus was applied during expiration (P < 0.05), and was unchanged when applied during inspiration (P > 0.05). These findings would suggest that cardiac vagal efferent activity was effectively inhibited by sensory stimulation during expiration, but was not inhibited by such stimulation during inspiration. This mechanism may account, in part, for the known suppression of respiratory cardiac cycle variability during exercise.

Calcitonin gene-related peptide increases in the dorsal root ganglia of adjuvant arthritic rat.

We examined the effect of adjuvant arthritis on the content of immunoreactive calcitonin gene-related peptide (iCGRP) in the dorsal root ganglia at L4-L6 levels and the spinal cord at a lumbar level in rats. Arthritis was induced by inoculating adjuvant into both hind-paws twice at a 10 day interval. In the arthritic rats 15 days after the first inoculation (day 15), the content of iCGRP was significantly increased in the dorsal root ganglia, with no change in the dorsal and ventral horns. The content in the dorsal root ganglia was still high on day 26 and had decreased by day 40. An intrathecal injection of colchicine (0.2 mg, 18 hr before killing) enhanced the increase of iCGRP in the dorsal root ganglia and decreased it in the dorsal horn of arthritic rats, although in noninoculated rats such treatment produced no significant changes in the content of iCGRP in both regions. The arthritis-induced increase in the content of iCGRP in the dorsal root ganglia was significantly reduced after treatment with the antiinflammatory analgesic, diclofenac sodium, in a dose of 3 mg/kg/day, PO for 10 days. Swelling and hyperalgesia in the hind-paw were depressed after such treatment. These results suggest that adjuvant arthritis with long-lasting inflammation with pain facilitates the turnover, especially biosynthesis, of CGRP in primary afferent neurons.