In vitro Anti-human Immunodeficiency Virus Type 1 Activity of Biliverdin, a Bile Pigment

Biliverdin (BY) is a bile pigment having anti-allergic properties. We examined the effect of BV on human immunodeficiency virus type 1 (HIV-1) in vitro. BV completely inhibited the cytopathic effect of HIV-1 in MT-4 cells at concentrations of 22.2 μ g/ml or more. This inhibitory effect was also observed when BV was present during the adsorption period of HIV-1. However, BV was cytotoxic to MT-4 cells at concentrations above 800 μ g/ml. At a concentration of 66.7 μ g/ml, BV completely inhibited syncytia formation by HIV-infected and uninfected MOLT-4 cells. Moreover, after exposure of HIV-1 particles to BV for 2 h, the infectivity of the virus was reduced in a dose-dependent manner. It is speculated that the anti-HIV activity of BV is due to direct inactivation of virions and inhibition of virus binding to target cells.     

Okadaic acid and phorbol esters: comparative effects of these tumor promoters on cell transformation, intercellular communication and differentiation in vitro

Okadaic acid is a non-12-O-tetradecanoylphorbol-13-acetate (TPA)-type tumor promoter in the mouse skin carcinogenesis system. Here we report on the in vitro activity of okadaic acid in 3 assay systems: BALB/c 3T3 cell transformation, gap junctional intercellular communication (GJIC) in various cell types, and inhibition of induction of differentiation of Friend virus-transformed murine erythroleukemia (MEL) cells. The activity of okadaic acid was compared to that of the phorbol ester tumor promoters TPA and phorbol-12,13-didecanoate (PDD). In a test system involving a 2-week exposure of BALB/c 3T3 cells following 3-methylcholanthrene initiation, okadaic acid at a concentration of 10 ng/ml was equipotent to PDD as a promoter of cell transformation (4.9 and 3.7 foci/dish, respectively). Longer exposures to okadaic acid resulted in cytotoxicity. Okadaic acid-generated as well as PDD-generated transformed foci displayed a selective lack of GJIC between focus cells and surrounding normal cells, i.e., transformed cells communicate among themselves but not with surrounding cells. However, in contrast to TPA, there was no inhibition by okadaic acid, except at toxic doses, of homologous GJIC in BALB/c 3T3 cells or human and mouse keratinocytes. Furthermore, okadaic acid, unlike TPA, did not inhibit MEL cell differentiation. Together, these results indicate that okadaic acid acts as a promoter of cell transformation but that its mechanism of action is different from that of the phorbol ester tumor promoters.     

A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and splenic metastasis

Pseudomyxoma peritonei (PMP) is a rare clinical entity in which a diffuse collection of intraperitoneal gelatinous fluid is associated with gelatinous implants on the peritoneal surfaces and omentum. Hematogenic or lymphatic metastasis is extremely rare. In addition, an inguinal mass as an initial presentation is also relatively rare. This is a case report of a PMP patient who had splenic metastasis and showed an inguinal tumor as an initial presentation. A 59-year-old female patient, who had undergone bilateral oophorectomy because of a ruptured ovarian mucinous tumor of boderline malignancy 12 years previously, presented a presumptive diagnosis of a left inguinal irreducible hernia. Computed tomography revealed a low density mass in the pelvic cavity and in the inguinal lesion, as well as in the spleen without any diseases around the organ. The preoperative serum carcinoembryonic antigen (CEA) level was elevated. The patient underwent a resection of gelatinous tumor in the pelvic cavity, splenectomy, and appendectomy, as well as left inguinal herniorrhaphy. Histological examinations revealed a splenic metastasis of PMP originating from the ovarian low-grade mucinous tumor. She received postoperative intraperitoneal lavage as well as chemotherapy, and has survived for over 7 years postoperatively without any evidence of recurrence, as confirmed by repeated follow-up CT examinations and CEA determination. Splenic metastasis of PMP is extremely rare; this represents only the third reported case of its kind in the literature. Furthermore, it should be noted that an inguinal tumor can sometimes be an initial presentation of PMP.     

Parameter estimation of respiratory impedance measured by forced complex-wave oscillations

Respiratory impedance data measured using the forced oscillation method were analyzed using an equivalent circuit model and the following conclusions were obtained: 1) Use of the complex wave oscillation method provided a measurement range of over 9 cmH2O/1/s with a resolution of 0.13 cmH2O/1/s. 2) The respiratory system was expressed as a two-compartment model. By expressing the circuit characteristics as phasor loci, a method was shown whereby individual impedance parameter values could be derived from the measured impedance phasor loci. 3) Under enflurane anesthesia, the model parameter values were derived as R1 = 1.2, R2 = 1.6 cmH2O/1/s, C1 = 0.02, C2 = 0.041/cmH2O and L = 0.065 cmH2O/1/s2.     

Molecular mechanisms of TPA-mediated inhibition of gap-junctional intercellular communication: evidence for action on the assembly or function but not the expression of connexin 43 in rat liver epithelial cells.

We found that a rat liver epithelial cell line (IAR 20) expresses connexin 43, the major cardiac gap-junction protein, but not connexin 26 or connexin 32, major liver gap-junction proteins. The effects of TPA on connexin 43 expression in IAR 20 were investigated using northern blot analysis, western blot analysis, and an immunofluorescence technique. Gap-junctional intercellular communication (GJIC) in this cell line decreased within 60 min of 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment and recovered after 24 h. The number of immunofluorescence spots of connexin 43 on IAR 20 was closely related to the change in GJIC induced by TPA. However, TPA did not change the level of mRNA measured by northern blot analysis. Moreover, connexin 43 protein expression analyzed by western blotting suggests that connexin 43 proteins were still present in TPA-treated cells at a similar level. These results suggest that GJIC of these rat liver epithelial cells was mediated by connexin 43 protein and that TPA inhibited GJIC by inhibiting posttranslational processing of connexin 43 proteins, e.g., localization or assembly.