Volume 112  ·   Issue 04  ·  1999

OBJECTIVE To assess serial changes of bone mass before and after orthotopic liver transplantation (OLT). METHODS Consecutive bone mineral density (BMD) of lumbar spine (L2-L4) and femoral neck in 38 patients with chronic liver failure within 2 months before OLT, 6, 12 and 24 months after OLT was determined using dual energy X-ray absorptiometry. RESULTS 29% of 38 patients before OLT had osteoporosis (BMD below 2 standard deviate). BMD levels at L2-L4 and femoral neck decreased and incidence of osteoporosis increased in the first 6 months after OLT. Over beyond 6 months post-OLT BMD levels at L2-L4 increased to just slightly above the pretransplant level and incidence of osteoporosis decreased from 36.8% (6 months after OLT) to 7.9% (24 months after OLT). Although BMD levels at femoral neck by 12 and 24 months after OLT gradually increased, BMD levels at femoral neck were still lower than those before OLT. CONCLUSIONS There was already a low bone mass in patients with chronic liver disease before OLT and liver transplantation induced a marked and rapid bone loss.

OBJECTIVE To explore the effect of mifepristone in treating ectopic pregnancy. METHODS Thirty-eight patients with ectopic pregnancy and without tubal rupture or tubal abortion, aged between 23 and 46 years, were studied. The stage of amenorrhoea ranged from 34 to 51 days. The patients took mifepristone at a dosage 2 times anti-early pregnancy dosage. The symptoms, and serum human chorionic gonadotropin (beta-hCG) levels were monitored, and ultrasonic examination performed at regular intervals. RESULTS Thirty-seven of 38 patients were cured, the success rate being 97.4%. CONCLUSIONS Mifepristone is safe and effective to treat ectopic pregnancy.

OBJECTIVE To detect the proliferative activity of cervical cells in cervical intraepithelial neoplasia (CIN) and cervical carcinoma by using proliferating cell nuclear antigen (PCNA) immunohistochemistry and mitotic index (MI). METHODS Sixty specimens of CIN and cervical carcinoma from patients treated at the Obstetrics and Gynaecology Hospital, Shanghai Medical University, were analyzed. Among them, 8 were CIN I-II, 16 CIN III, 18 squamous carcinoma, and 18 adenocarcinoma. Serial 4 microns sections were prepared for haematoxylin and eosin (HE) staining to observe mitotic figure and pathological grading and for immunohistochemical staining of PACN which was performed by murine monoclonal antibody PC 10 (DAKO-PCNA). RESULTS PCNA index (PI) and MI of CIN III and cervical carcinoma were significantly higher than those of normal cervix and CIN I-II. PI and MI increased with progress of disease. In addition, higher level of PI was correlated with higher level of MI, and higher levels of PI and MI were related with higher histological grade. However, there was no significant relationship between PI, MI, clinical staging, and lymph node metastases. CONCLUSIONS PCNA and mitotic figure are useful for evaluating proliferative activity in CIN and cervical carcinoma, and could be used to distinguish CIN III from CIN I-II and evaluate the malignant potential of tumour tissues.

OBJECTIVE To investigate the special effect of donor antigen-trichosnthin (TCS) conjugate on depleting the immune reactive cells that respond to xenograft, and thus inducing specific xenograft tolerance. METHODS Rat anti-mouse antibodies coupled sepharose-4B beads were used to purify mouse H-2 antigens by affinity chromatography. Those purified H-2 antigens were conjugated with TCS by heterobifunctional reagents SPDP [3-(2-pyridyldithio) propionic acid-hydroxysuccinimide ester] and 2-IT (2-iminothiolane). The specific inhibition function of Ag-TCS to recipient's immune cells was measured in vitro. Ag-TCS conjugate (200 micrograms/kg, i.v.) was administered to the recipients (rats) 4 days prior to cardiac xenotransplantation of mouse to rat. RESULTS In vitro, the proliferation of immune reactive cells in the recipients pretreated with Ag-TCS was inhibited. The Ag-TCS conjugate significantly prolonged the cardiac survival time (6.88±1.36 days) compared with cyclosporine A (CsA) group (2.83±0.75 days) (P<0.01). CONCLUSIONS Donor Ag-TCS conjugate can induce specific tolerance to xenograft.

OBJECTIVE To investigate the relationship between intercellular adhesion molecule-1 (ICAM-1) and the accumulation of eosinophils in nasal polyp tissue to better understand the mechanism of airway eosinophilic inflammation. METHODS The expression of ICAM-1 and its natural ligand, lymphocyte function-associated antigen-1 (LFA-1), in normal nasal mucosa from 6 controls and in nasal polyp tissue from 19 patients with nasal polyposis were determined with immunohistochemistry. With dual immunohistochemistry and May-Griünwald Giemsa stain (MGG), the expression of LFA-1 and infiltrating eosinophils in nasal polyp tissue was observed. RESULTS The expression of ICAM-1 and LFA-1 was stronger in the nasal polyp tissue than in normal nasal mucosa. There was a positive relationship between the infiltration of eosinophils and the expression of LFA-1 on eosinophils. CONCLUSIONS Accumulation of eosinophils in nasal polyp tissue is associated with the counter-effect between adhesion molecules and its ligand on eosinophils.

OBJECTIVE To study the interrelation between nitric oxide (NO) and endothelin-1 (ET1) in experimental acute hypoxic rats, and to evaluate the mechanism of acute hypoxic pulmonary hypertension affected by NO and ET1 and its intervention. METHODS Nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical staining method, Griess biochemical assay and radioimmune assay were applied to investigate the changes of nitric oxide syntheses (NOS), NO and ET1 in normal, hypoxic, and L-Arginine (L-Arg) and dexamethasone treated hypoxic rats. RESULTS In normal rats, the NOS stain was localized in pulmonary vascular endothelium, and in the hypoxic rats, the activity of NOS was significantly lower. The level of plasma NO was significantly lower during acute hypoxia, but L-Arg as well as dexamethasone could prevent the drop of plasma NO. The level of plasma ET1 rose up significantly in the acute hypoxic rats, but after L-Arg therapy, it was significantly reduced, however, dexamethasone could not affect plasma ET1. The level of plasma cyclic guanosine monophosphate (cGMP) was significantly lower in the acute hypoxic rats, and L-Arg could prevent the drop of plasma cGMP, but dexamethasone could not prevent the drop of plasma cGMP. CONCLUSIONS NO and ET1 may modulate hypoxic pulmonary hypertension and acute hypoxia can result in acute hypoxic pulmonary hypertension. L-Arg can reverse the acute hypoxic pulmonary hypertension. Further study is needed if dexamethasone is beneficial in acute hypoxic diseases. NO may play an important role in physiology of the lung and acute hypoxic diseases.

OBJECTIVE To investigate the role of purinergic P2Z receptors for apoptosis of human leukemic lymphocytes mediated by extracellular adenosine triphosphate (ATP). METHODS A total of 13 B-chronic lymphocytic leukemia (CLL) patients were studied. Exposure of leukemic lymphocytes with (n = 8) or without (n = 5) P2Z receptors to ATP, benzoylbenzoic-ATP (BzATP), 2-methylthio-ATP (2MeSATP), adenosine-5' [gamma-thio] triphosphate (ATP-gamma S), and other nucleosides for 8 h in vitro. Apoptosis was detected by electron microscopy (EM), agarose gel electrophoresis, and the quantitative assay-TdT assay. RESULTS Apoptosis was detected only in leukemic lymphocytes with P2Z receptors. Using a quantitative assay, ATP-induced DNA strand breaks were found to occur specifically with BzATP, ATP and 2MeSATP, but not for analogue ATP-gamma S nor other nucleosides. Meanwhile, ATP-induced DNA fragmentation was fully blocked by pretreatment with oxidized ATP (OxATP), a compound recently shown to block P2Z receptors. Also, it is shown that the Ca2+/calmodulin complex plays a role in the regulation of the apoptosis induced by ATP on CLL cells, because an antagonist of this complex, 1-[N, O-bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) was found to inhibit the ATP-induced apoptosis. Furthermore, choline, an inhibitor of phospholipase D (PLD), is first shown to partially inhibit ATP-induced apoptosis. CONCLUSIONS These data indicate that P2Z receptors on lymphocytes play an important role in the apoptosis induced by ATP in vitro.

OBJECTIVE To use NB4, an authentic human acute promyelocytic leukemia cell line, as well as the marrow cells from patients with acute promyelocytic leukemia (APL), containing the PML/RAR alpha fusion gene and fused protein to examine the growth inhibition and cytodifferentiation induced by all-trans retinoic acid (ATRA), butyric acid (BA) and its prodrug tributyrin (TB) either as a single agent or in combinations. METHODS NB4 and APL cells were cultured in presence of ATRA, BA and TB respectively either as a single agent or in combinations at various concentration ratio. Cell growth was measured and myeloid differentiation was determined by morphology and the percentage of positive nitroblue tetrazolium reduction (NBT) on consecutive days over the whole process of culture. RESULTS NB4 cells can be induced by ATRA alone and synergistically induced by the combinations of BA or TB with ATRA to differentiate. The synergy was reflected by a remarkable decrease in the effective concentration of ATRA required in the combinations in comparison with it as a sole agent. The combinations also shortened the time for the cells to reach the same level of maturation as that needed for ATRA alone. The potentiation on ATRA-induced differentiation of NB4 cells seemed depending on an appropriate concentration ratio of each inducer in the combinations and the time of action. A preliminary result of in vitro induction of primarily cultured leukemic cells from APL patients by the combined inducers was promising. CONCLUSIONS The combinations of ATRA with BA or TB at an appropriate ratio may improve the clinical outcome of differentiation therapy for APL patients.

OBJECTIVE To prepare a kit for screening individuals with glucose-6-phosphate dehydrogenase (G6PD) defect. The kit is easy to use and to get the fast as well as reliable results. Especially it is suitable for the anti-malaria spots usually located in the remote countryside where no electricity is available. METHODS The double filter paper method and other 2 techniques, the quantitative method and the single filter paper method, were used to determine G6PD activity in 70 samples of human erythrocytes. It was found that the results of the double filter paper method and those of the single filter paper method in the first 8 hours after the drying of the blood-soaked filter paper were consistent with those of the quantitative method. When a piece of blood-soaked paper is left under room temperature more than 24 hours, G6PD in the erythrocytes deteriorated spontaneously and consequently the number of positive cases increased along with the elapse of time. RESULTS Satisfactory results were achieved when the kit was used to screen cases of G6PD defect from 151 farmers who were receiving anti-malaria therapy. The kit was made according to a technique named "double filter paper" method. CONCLUSIONS These findings suggest that the double filter paper method can reveal the level of G6PD activity and the results are rapidly obtained when the method is used on the anti-malaria spot.

OBJECTIVE To observe the therapeutic effects of triclabendazole in the treatment of dogs with Paragonimiasis westermani. METHODS Six dogs were experimentally infected, each with 100 metacercariae of Paragonimus westermani intraperitoneally and divided into untreated and treated groups, 3 dogs were treated orally with triclabendazole 100 mg/kg.d-1 for 2 consecutive days on day 170 after infection. Stool egg count was done by Stoll method. All dogs were killed on day 38 after treatment and the number of worm cysts and worms in the lungs were examined by naked eye and microscopically. RESULTS Stool eggs became negative from day 7 to day 14 after starting chemotherapy in treated dogs. The numbers of worm cysts in the lungs of untreated dogs were 18, 24 and 24 on necropsy, while those in the treated dogs were 10, 7 and 4, respectively. The numbers of adult worms in the untreated dogs were 38, 51 and 42, while in the treated dogs only 2 small adult worms were found in one dog and no worm was found in the other two dogs. The mean worm reduction rate was 98.5%. CONCLUSIONS Triclabendazole is highly effective against Paragonimus westermani in experimentally infected dogs.

Purpose Both oncogenic viruses and cell cycle control proteins are fast-growth research areas. More and more evidence indicates that virus infection and replication are often associated with apoptosis and interfere with cell cycle pathways. To understand the mechanisms by which viral proteins regulate apoptosis and target the cellular pathways may lead to the development of new remedies for some cancers. Data source English literature searched by MEDLINE from January 1995 to August 1998. Study selection and data extraction More than one hundred research papers published in these areas over the past three years. Only new and important breakthroughs in these papers are selected. The review focuses on DNA viruses associated with the development of human cancers. Results and conclusions Some DNA viruses contain oncogenic proteins which transform normal cells in vitro and induce tumors in animals. These viral proteins target the cellular pathways and block apoptosis induced by receptors or in response to signal transduction. Viral interference with host cell apoptosis leads to enhanced viral replication and may promote carcinogenesis. Oncogenes and tumor suppressor genes, such as Retinoblastoma (RB) and p53, play important roles in regulation of these interactions.