C3 production of cultured human epidermal keratinocytes is enhanced by IFNgamma and TNFalpha through different pathways.

We investigated the regulation of C3 production by human cultured epidermal keratinocytes by enzyme-linked immunosorbent assay. The results showed that IFNgamma and TNFalpha enhanced the synthesis of C3 by epidermal keratinocytes in a concentration-dependent manner. Moreover, a protein kinase C (PKC) inhibitor blocked C3 production, whereas PMA enhanced it.

Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups.

Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity (IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).

Regulation of human immunodeficiency virus gp160-mediated cell fusion by antibodies against fusion regulatory protein 1.

We have isolated new MAbs directed against the human fusion regulatory protein 1 (FRP-1; CD98) molecule using human FRP-1-expressing L929 cells as antigens. The biological activities, and in particular the human immunodeficiency virus (HIV)-mediated fusion regulatory activity of seven anti-FRP-1/CD98 MAbs were analysed using the U937/gp160 cell line, which is a CD4+ U937 cell line expressing HIV gp160. Two MAbs induced multinucleated giant cell formation in U937/gp160 cells and the other five MAbs showed no fusion-inducing ability.

Rhabdomyolysis following administration of cyclophosphamide: a case report in a BMT recipient.

Massive rhabdomyolysis followed by myocardial necrosis was observed in a 14-year-old patient undergoing allogeneic bone marrow transplantation for severe aplastic anemia. Rhabdomyolysis was preceded by the administration of cyclophosphamide as part of a preparative regimen for transplantation Although the specific etiology of this rhabdomyolysis is still unknown, an association with high-dose cyclophosphamide should be noted.

Intracellular localization of antigens recognized by anti-vimentin monoclonal antibodies (mAbs): cross-reactivities of anti-vimentin mAbs with other cellular components.

Monoclonal antibodies were raised against immunoaffinity-purified fusion regulatory protein (FRP)-1 complex from membrane fraction of HeLa cells. Immunoblotting and immunoprecipitation studies showed all ten antibodies reacted with a 55 kDa band of cell lysate and purified vimentin. Interestingly, one of the antibodies (mAb57) cross-reacted with purified tropomyosin and myosin.

Epidemiology and prognosis of subungual melanoma in 34 Japanese patients.

The incidence of malignant melanoma is much lower in the Japanese than in caucasians. However, amongst the various types of malignant melanoma, the subungual and periungual sites are commonly found in the Japanese. One hundred and fifty-one cases of cutaneous malignant melanoma were seen over a 25-year period at our hospital.

Pyripyropenes, novel ACAT inhibitors produced by Aspergillus fumigatus. IV. Structure elucidation of pyripyropenes M to R.

Six new pyripyropenes, M to R, were isolated from the ethyl acetate extracts of the jar fermentation broth of Aspergillus fumigatus FO-1289-2501. Structural elucidation indicated that all the pyripyropenes have the same pyridino-alpha-pyrone sesquiterpene core as pyripyropenes A to L. Among them pyripyropene M showed the most potent inhibition against acyl-CoA : cholesterol acyltransferase activity with an IC50 value of 3.

Xanthoquinodin B3, a new anticoccidial agent produced by Humicola sp. FO-888.

Xanthoquinodin B3, a new component of anticoccidial xanthoquinodins, which was detected in the culture broth of Humicola sp. FO-888, was isolated by heat treatment of the xanthoquinodins complex. Structural elucidation indicated that xanthoquinodin B3 has the same heterodimer of xanthone- and anthraquinone-derived monomers as other xanthoquinodins.

New isochromophilones VII and VIII produced by Penicillium sp. FO-4164.

New isochromophilones VII and VIII were isolated from the culture broth of Penicillium sp. FO-4164. The structures were elucidated as 6H-2-benzopyran-6,8(7H)-dione, 5-chloro-3-(3',5'-dimethyl-1',3'-heptadienyl)-1,7,8a-trihydro-7, 8a-dihydroxy-7-methyl-7-acetate for isochromophilone VII and 6H-2-benzopyran-6-one,5-chloro-3-(3',5'-dimethyl-1', 3'-heptadienyl)-1,7,8,8a-tetrahydro-7,8-dihydroxy-7-methyl-8-acetate for isochromophilone VIII.

Clinicopathological study of acral melanoma in situ in 44 Japanese patients.

Background: Acral lentiginous melanoma (ALM) has been a major focus of interest in Japan in the last 2 decades. A remarkable improvement recently made in the prognosis of ALM at our institution may possibly be explained by early detection including melanoma in situ.

Objective: We have retrospectively studied 44 cases of melanoma in situ in the past 25 years from 1970 to 1994, 61% of which have been seen in the last 5 years.

Identification of fusion regulatory protein (FRP)-1/4F2 related molecules: cytoskeletal proteins are associated with FRP-1 molecules that regulate multinucleated giant cell formation of monocytes and HIV-induced cell fusion.

Fusion regulatory proteins (FRPs) regulate virus-mediated cell fusion and multinucleated giant cell formation of monocytes. Anti-FRP-1 mAbs immunoprecipitated 80 kDa and 38 kDa proteins from HeLa cells. After long exposure other bands were detected, suggesting the presence of molecule(s) associated with FRP-1.

Successful bone marrow transplantation in a child with combined IgG subclass deficiency and neutropenia.

An 8-year-old boy with combined IgG1 deficiency and neutropenia underwent allogeneic BMT from his HLA-identical, MLC-negative sister, because immunoglobulin (Ig) infusions and prophylactic antibiotics failed to prevent life-threatening infections. Conditioning was with busulfan and cyclophosphamide, MTX and CYA were given for the prophylaxis of GVHD. For 16 months after BMT no serious infections have occurred and serum IgG1 levels have returned to the normal range without Ig replacement.

On an accident by liquid nitrogen--histological changes of skin in cold.

Two young researchers were found lying beside 3 Dewar flasks for liquid nitrogen in a cold experimental room of a university. They were sent to a hospital but died 1.5 h after cardiopulmonary resuscitation.

Identification of regions on the hemagglutinin-neuraminidase protein of human parainfluenza virus type 2 important for promoting cell fusion.

The hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of two paramyxoviruses, human parainfluenza virus type 2 (PIV2) and simian virus 41 (SV41), were expressed in HeLa cells by transfecting with recombinant plasmid harboring each glycoprotein gene. Expressed F proteins could not induce cell fusion by themselves, but evoked prominent cell fusion when coexpressed with homologous HN proteins. It was also proved that PIV2 HN protein could weakly promote SV41 F-mediated cell fusion.

Nodular melanoma in 62 Japanese patients: influence of initial surgical treatment on local recurrence and prognosis.

The incidence of malignant melanoma is much lower in Japanese than in Caucasians, and the commonest type of melanoma in Japanese is acral lentiginous melanoma (ALM). In contrast to the improved prognosis noted in ALM, it is now of increasing concern that there is a rise in both the frequency and mortality of nodular melanoma. During the 25 years from 1970 to 1994, we observed 190 patients with melanoma, including 62 nodular melanomas and 96 ALM, at the Department of Dermatology, Tohoku University Hospital, Sendai, Japan.

Molecular characterization of fusion regulatory protein-1 (FRP-1) that induces multinucleated giant cell formation of monocytes and HIV gp160-mediated cell fusion. FRP-1 and 4F2/CD98 are identical molecules.

Fusion regulatory protein (FRP)-1 regulates virus-mediated cell fusion and fusion of monocytes. Eleven of fifteen N-terminal amino acids of FRP-1 were the same as the amino acid sequence of 4F2/CD98 heavy chain. FRP-1 molecules were detected in Con A- or IL-2-stimulated lymphocytes, while FRP-1 was rare on resting lymphocytes.

Amidepsines, inhibitors of diacylglycerol acyltransferase produced by Humicola sp. FO-2942. II. Structure elucidation of amidepsines A, B and C.

Structures of amidepsines A, B, C and D, diacylglycerol acyltransferase (DGAT) inhibitors, were determined by spectroscopic studies including various NMR measurements. They were elucidated as 2-hydroxy-4-[[2-hydroxy-4-[(2,4-dimethoxy-6-methylbenzoyl) oxy]6-methylbenzoyl]-oxy]-6-methylbenzoic acid N-alanine amide for amidepsine A, 2-hydroxy-4-[[2-hydroxy-4-[(2-hydroxy-4-methoxy-6-methylbenzoyl) oxy]6-methylbenzoyl]oxy]-6-methylbenzoic acid N-alanine amide for amidepsine B and 2-hydroxy-4-[[2-hydroxy-4-[(2-hydroxy-4-methoxy-6-methylbenzoyl) oxy]6-methylbenzoyl]oxy]-6-methylbenzoic acid N-valine amide for amidepsine C. Amidepsine D was identified with 2,4-di-O-methylgryphoric acid.

Amidepsines, inhibitors of diacylglycerol acyltransferase produced by Humicola sp. FO-2942. I. Production, isolation and biological properties.

Humicola sp. FO-2942, a soil isolate, was found to produce a series of new inhibitors of diacylglycerol acyltransferase (DGAT). Three active compounds, designated amidepsines A, B and C, were isolated from the fermentation broth of the producing strain by solvent extraction, silica gel column chromatography, ODS column chromatography and HPLC.

Terpendoles, novel ACAT inhibitors produced by Albophoma yamanashiensis. III. Production, isolation and structure elucidation of new components.

Eight new components of terpendoles E to L were isolated and characterized from the culture broth of Albophoma yamanashiensis using a different production medium. All the structures were elucidated by spectroscopic analyses including various NMR experiments, indicating that all the terpendoles have the same indoloditerpene core as terpendoles A to D. Terpendoles J, K and L showed the moderate inhibition against acyl-CoA: cholesterol acyltransferase (ACAT) activity with IC50 values of 38.

Isochromophilones III-VI, inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium multicolor FO-3216.

New azaphilones named isochromophilones III-VI were isolated from the culture broth of Penicillium multicolor FO-3216 as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT). Their structures were elucidated by NMR and other spectroscopic analyses. The IC50 values of isochromophilones III, IV, V and VI for ACAT activity in an enzyme assay using rat liver microsomes were calculated to be 110, 50, 50 and 120 microM, respectively.

Successful treatment of an infant with veno-occlusive disease developed after allogeneic bone marrow transplantation by tissue plasminogen activator, heparin and prostaglandin E1.

A 15-month-old boy with severe aplastic anemia developed veno-occlusive disease (VOD) after allogeneic bone marrow transplantation (BMT), in which the preparative regimen included 50 mg/kg/day cyclophosphamide and anti-lymphocyte globulin for 4 consecutive days. The diagnosis was made based on clinical symptoms and data including, hepatomegaly, right upper quadrant abdominal pain, jaundice, ascites, coagulopathy and thrombocytopenia which was refractory to transfusions of platelet concentrate. We gave 2, 3, 5 and 5 mg/day/body of recombinant tissue plasminogen activator (tPA) followed by heparin and prostaglandin E1 (PGE1) effectively and without significant side effect on days 9, 10, 13 and 14, respectively.