Intrahepatic portosystemic venous shunt associated with biliary atresia: case report

We describe an infant with intrahepatic portosystemic venous shunt (IPSVS), which was detected by MR angiography. IPSVS is rare and its cause is disputed. However, with improvements in imaging the number of reports of IPSVS identified incidentally in patients without definite symptoms is increasing. The present case is the first associated with congenital biliary atresia and the youngest reported in the literature. Received: 1 August 1999/Accepted: 16 August 1999     

Ethanol exposure induces oxidative stress and impairs nitric oxide availability in the human placental villi: a possible mechanism of toxicity

OBJECTIVE: We undertook this investigation to explore the effects of ethanol exposure on nitric oxide synthase levels and nitric oxide release. Our hypothesis was that ethanol exposure modifies nitric oxide activity within the placenta as a result of oxidative stress. STUDY DESIGN: Four 10-g samples of term normal human placental villous tissue were perifused with nonrecirculating Dulbecco's modified Eagle's medium and 25-mmol/L N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid] with 0-, 50-, 100-, or 200-mmol/L ethanol. After 2 hours of exposure, tissue was removed, fixed, and frozen for analysis. Immunohistochemical analysis was performed for subtype I or neuronal nitric oxide synthase (nNOS), subtype II or inducible nitric oxide synthase (iNOS), and subtype III or endothelial nitric oxide synthase (eNOS) localization. Western blot analysis was performed for eNOS quantitation. Cyclic guanosine monophosphate and copper-zinc superoxide dismutase levels were measured by electroimmunoassay and kinetic assay, respectively. Nitric oxide release was analyzed by a Sievers nitric oxide analyzer. RESULTS: Immunohistochemical examination confirmed that only eNOS was localized to the syncytiotrophoblasts. After ethanol exposure, eNOS protein expression increased 2.5- to 3.0-fold over that of the control. Tissue cyclic guanosine monophosphate content and nitric oxide release into the effluent were decreased, whereas superoxide dismutase levels were increased at higher ethanol levels (P <.05). CONCLUSION: Ethanol exposure appears to induce oxidative stress, which may account for the decreased nitric oxide release, because nitric oxide may be shunted toward scavenging free radicals. Increased eNOS protein expression may be a response to the increased demand for nitric oxide. Decreased nitric oxide availability could adversely affect placental blood flow regulation, which could, in turn, account for the growth restriction seen in ethanol-exposed fetuses.     

Triazine Derivatives Inhibit Rat Hepatocarcinogenesis but Do Not Enhance Gap Junctional Intercellular Communication

We report here novel candidate chemopreventive agents active against experimental hepatocarcino-genesis. The triazine derivatives 6-(2-chlorophenyl)-2,4-diamino-l,3,5-triazine (2CPDAT), 6-(3-chlorophenyl)-2,4-diamino-l,3,5-triazine (3CPDAT), 6-(4-chlorophenyl)-2,4-diamino-l,3,5-triazine (4CPDAT), 6-(4-pyridyl)-2,4-diamino-l,3,5-triazine (PyDAT), and 6-(pyridine JV-oxid-4-yl)-2,4-diamino-l,3,5-triazine (PyNODAT), synthesized in our laboratory, in addition to 6-(2,5-dichloro-phenyl)-2,4-diamino-l,3,5-triazme (DCPDAT), or irsogladine, which is a widely used anti-ulcer drug, were investigated for potential chemopreventive effects in a rat liver medium-term bioassay system. A significant inhibitory influence on enzyme-altered liver foci was found for 2CPDAT, 3CPDAT, 4CPDAT, and PyNODAT, but not for DCPDAT or PyDAT, The involvement of gap jnnctional intercellular communication in the inhibition was studied, but no change in gap Junctional intercellular communication capacity in rat liver cells in vitro or in gap junction protein (connexin 32) expression in rat liver in vivo was noted. These results indicate that, although these irsogladine analogues exert inhibitory effects on rat liver carcinogenesis, their action is independent of modification of gap Junctional intercellular communication.     

In vivo Retrovirus-mediated Herpes Simplex Virus Thymidine Kinase Gene Therapy Approach for Adult T Cell Leukemia in a Rat Model

We have previously demonstrated that human T-lymphotropic virus type I (HTLV-tax-expressing human T cell lines are selectively eliminated in the presence of aciclovir, using a retroviral vector carrying the herpes simplex virus thymidine kinasc (HSV TK) gene under the control of the long terminal repeat (LTR) of HTLV-I. Based on these findings in vitro , we investigated whether this system could also be effective in vivo , using a rat model. Following infection of the HTLV-I-trans-formed and tot-expressing rat T cell line TARS-1 with this retrovirus (LNLTK virus), high levels of HSV TK expression were observed and resulted in increased susceptibility to ganciclovir (GCV). Tumors were generated by subcutaneous injection of TARS-1 in newborn syngeneic WKA/H rats. While the tumors derived from infected TARS-1 cells with control virus, as well as uninfected cells, continued to grow in all the rats with or without administration of GCV, those derived from LNLTK-infected cells exhibited dramatic regression upon GCV treatment. These results indicate that the HTLV-I LTR-HSV TK system also causes selective elimination of HTLV-I-transformed, (ax-expressing T cells in vivo. Therefore, our present study may provide a rationale for clinical gene therapy against adult T cell leukemia.     

Induction of Specific Cytotoxic T Lymphocytes against Autologous Brain Tumor by Crossreactive Allo-tumor Cell Stimulation

Cytotoxic T lymphocytes (CTL) against autologous malignant brain tumor were generated in peripheral blood lymphoid cells (PBL) prepared from a patient with a malignant brain tumor by stimulation of the cultured PBL for 7 days with attenuated Crossreactive malignant melanoma (MM2) cells pretreated with mitomycin C. The Crossreactive MM2 cells were effective for antigen stimulation for CTL induction in place of autologous glioblastoma cells, which are difficult to expand in culture. The optimal ratio between nylon wool-passed T lymphocytes and nylon wool-adherent accessory cells to induce CTL in the patient's PBL was found to be 25 to 1. In vitro -activated CTLs induced by MM2 were cytotoxic not only to MM2, but also to the autologous tumor cells in an HLA class I-restricted manner, and their surface phenotype was found to be CD3⁺ and CD8⁺. CTL therapy using cross-reactive allogeneic tumor cells as the stimulator could be clinically valuable to treat malignant brain tumors.     

Comparison of Cytology and Cervkography in Screening a High Risk Australian Population for Cervical Human Papillomavirus and Cervical intraepithelial Neoplasia

Summary: Two different screening methods, the Papanicolaou (Pap) smear and cervigram were compared in screening 245 Sydney women over a 6-month period in 1988 at a city sexually transmitted diseases (STD) centre, for cervical human papillomavirus (HPV), cervical intraepithelial neoplasia (CIN) and cervical cancer. The Pap smear through the identification of cytologically abnormal cells correctly detected 54% of cases of histologically proven CIN and 39.2% of cases of HPV. The cervigram through the identification of acetowhite epithelium and/or abnormal vessels on the cervix correctly detected 64% of cases of histologically proven CIN and 70.6% of cases of HPV. However, when both tests were used together, 92% of CIN lesions and 82.4% of HPV lesions were correctly identified. Histology of a colposcopically directed biopsy was used as the 'gold standard'. The sensitivity and specificity of the Pap smear after correction for verification bias was 46% and 78% respectively, and for the cervigram was 49% and 60% respectively. Hence neither screening test appears adequate on its own, at least in an STD population.     

Fetal sheep in utero hear through bone conduction

Purpose: Although the air-conduction pathway is the principal mode of sound transmission to the inner ear, this may not be true for the fetus in utero. The fetus detects and responds to sounds in the maternal environment. Exogenous sounds can reach the fetal inner ear through the ear canal and middle ear system, bone conduction, or both. This study was designed to compare the effectiveness of these two routes of sound transmission by recording cochlear microphonic potentials from the fetus in utero in response to airborne sounds.Materials and Methods: Cochlear microphonics (CMs) recorded from one round window (RW) of fetal sheep in utero were obtained in three conditions: (1) head uncovered; (2) head covered with a neoprene hood; and (3) head covered with a neoprene hood fashioned with a hole that permitted the pinna and ear canal to be exposed. Tone bursts (0.5, 1.0, and 2.0 kHz) were delivered through a loudspeaker at high intensities (100 to 135 dB sound pressure level) to the flank of the ewe. CMs were detected with indwelling electrodes, amplified, and averaged. CM input-output functions were obtained from the fetus in each of the three conditions described above.Results: CMs recorded with the head uncovered were more sensitive than were the CMs recorded with the hood in place. There was no difference in sensitivity between the condition during which the head was completely covered and the condition in which the pinna and ear canal canal are exposed.Conclusion: The principal mode of sound transmission into the fetal inner ear is through bone conduction.