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Biomedical subjects

X H Liu

Publications and source records attributed to X H Liu.

At least 145 records · Page 8Linked to original sources

Protective effect of bifemelane hydrochloride on ischemic hippocampal CA1 neuronal damage in the gerbil: relation to induction of HSP70.

A protective effect of bifemelane hydrochloride (BF) on hippocampal CA1 neuronal death in gerbils was investigated following transient forebrain ischemia in relation to the induction of 70-kd heat shock protein (HSP70) and its mRNA. Histological examination showed that the neuronal density of the hippocampal CA1 sector treated with 10 and 30 mg/kg of BF (i.p.) was higher than that of the vehicle (p < 0.05 and p < 0.01, respectively) at 7 days after ischemia. Immunohistochemistry against HSP70 protein and in situ hybridization for the mRNA revealed that the inductions of immunoreactive HSP70 and the mRNA were remarkably reduced and limited in the brain hippocampi treated with BF (30 mg/kg) as compared with vehicle-treated animals. These data indicate that BF possesses a protective effect against ischemic injury to the vulnerable CA1 neurons. The possible mechanisms of the protection are discussed.

Animals↗

Androgens regulate proliferation of human prostate cancer cells in culture by increasing transforming growth factor-alpha (TGF-alpha) and epidermal growth factor (EGF)/TGF-alpha receptor.

Androgens affect growth of the prostate gland and many prostate cancers. Androgens could mediate their mitogenic effects on prostate cells by an autocrine loop involving epidermal growth factor (EGF) and transforming growth factor (TGF)-alpha that bind to the EGF/TGF-alpha receptor. We examined the effects of 5 alpha-dihydrotestosterone (DHT) and testosterone (T), EGF, and EGF-alpha on cell proliferation and 3H-thymidine incorporation in an androgen-dependent human prostate cancer cell line, ALVA101, in serum-free medium. The regulation of TGF-alpha and EGF/TGF-alpha receptor messenger RNA (mRNA) levels were determined by Northern blot analysis and EGF/TGF-alpha receptor protein by immunoblot. After 24 h of treatment of ALVA101 cells with DHT (10(-8) M) or T (10(-8) M), TGF-alpha mRNA levels increased 3- and 2.5-fold, respectively, and EGF/TGF-alpha receptor mRNA levels 2- and 1.5-fold, respectively. Cell numbers increased at day 5 in response to 10(-8) M DHT (18%, P < 0.01), 10(-8) M T (15%, P < 0.01), 20 ng/ml EGF (16%, P < 0.01), and 50 ng/mL TGF-alpha (34%, P < 0.01). DHT combined with TGF-alpha or T combined with EGF increased cell number 43% and 40% above control, respectively (P < 0.01 vs. DHT, P < 0.05 vs. TGF-alpha, T, EGF alone). The anti-EGF/TGF-alpha receptor antibody (528) blocked the cell proliferation induced by either DHT or TGF-alpha. We conclude that DHT and T stimulate synthesis of TGF-alpha and EGF/TGF-alpha receptor mRNAs and EGF/TGF-alpha receptor content in ALVA101 cells. This mitogenic effect of androgen on ALVA101 cells may involve TGF-alpha and the EGF/TGF-alpha receptor autocrine loop.

Androgens↗

The prognostic value of the HNK-1 (Leu-7) antigen in prostatic cancer--an immunohistochemical study.

The anti-HNK-1 (Leu-7) monoclonal antibody (MAb) was revealed to be reactive with noncancerous and cancerous prostatic epithelial cells, although this antibody was originally found to be reactive against natural killer cells. However, the prognostic significance of HNK-1 antigen in prostatic cancer patients remains unknown. The expression of HNK-1 antigen on prostatic cancer was investigated immunohistochemically using the avidin-biotin-peroxidase complex (ABC) method with the anti-HNK-1 monoclonal antibody. Of the 52 patients with prostatic cancer, 49 patients (94%) showed reactivity to anti-HNK-1 MAb and the immunoreaction was associated with the histological differentiation of prostatic cancer. Well differentiated cancer showed the highest percentage of positively stained cancer cells and poorly differentiated cancer showed the lowest percentage. No statistically significant differences existed between groups classified by stage, although the more advanced cancers tended to have weaker reactions. The five-year survival rate and interval free of progression were then studied using the Kaplan-Meier method on 33 patients with stage D2 disease who had received endocrine therapy. The findings indicated that a high survival rate and a longer interval free of progression were associated with a higher fraction of positively stained cancer cells. In conclusion, the expression of HNK-1 antigen on prostatic cancer may be a useful prognostic factor in patients with prostatic cancer.

Adult↗

Adjustment for non-differential misclassification error in the generalized linear model.

It is well known that estimates of association between an outcome variable and a set of categorical covariates, some of which are measured with misclassification, tend to be biased upon application of the usual methods of estimation that ignore the classification error. We propose a method to adjust for misclassification in covariates when one applies the generalized linear model. In the case where one can observe some true covariates only through surrogates, we combine a latent class analysis with the approach to incorporate multiple surrogates into the model. We include discussion on the efficacy of repeated measurements which one can view as a special case of multiple surrogates with identical distribution. We provide two examples to demonstrate the applicability of the method and the efficacy of multiple replicates for a covariate subject to misclassification in a regression framework.

Adolescent↗

Correlation of mutations of oncogene C-Ha-ras at codon 12 with metastasis and survival of gastric cancer patients.

Mutations of c-Ha-ras at codon 12 were detected from 11 out of 27 fresh tissues and cell-lines of human gastric cancer patients using PCR-restriction analysis. Further statistical investigation showed that the presence of point mutations was related to the distal metastases and the survival time of gastric cancer patients after surgical operations.

Electrophoresis, Polyacrylamide Gel↗

[Pharmacokinetics of norethindrone enanthate 200 mg after intramuscular injection in 25 Chinese women].

Pharmacokinetic profile was studied in 25 healthy fertile Chinese female volunteers after im norethindrone enanthate (NET-EN) 200 mg. The results were compared with the data from British women in our previous paper. Following a single im NET-EN 200 mg, the times to reach peak levels of NET-EN and NET were 4.0 +/- 2.8 d and 5.4 +/- 2.0 d, and their peak values were 5.0 +/- 1.8 and 12.6 +/- 0.9 ng.ml-1, respectively. Mean elimination T1/2 of NET was significantly longer than that of NET-EN. Mean apparent elimination T1/2 were 14.8 +/- 3.8 d for and 11.4 +/- 5.7 d for NET-EN. The elimination rate of NET in Chinese women was significantly slower than that in British women. There was no significant ethnic difference in absorption kinetics of NET and NET-EN.

Adult↗

Elliptinium, norcantharidin and tetrachlordecaoxide in combined chemo-immunotherapy prolong the survival of Friend-virus-infected mice.

The association of several drugs with different target specificities has long been proven to be more efficient than one single agent in the treatment of cancer. This strategy might also be of benefit in the cure of retrovirus-induced diseases. The effectiveness of several drug combinations was evaluated on DBA/2 mice injected with Friend leukaemia virus (FLV). Elliptinium (ELP), a known chemotherapeutic agent with possible antiviral activity, was given in association with norcantharidin (NCTD) (shown previously to increase the cytotoxic potential of human lymphocytes) and/or in association with tetrachlordecaoxide (TCDO), which augments both humoral and cellular immune responses. ELP alone at a dose of 0.2 mg/kg in long-term treatment significantly increased the survival of mice infected by FLV. When ELP, TCDO (2 micrograms/kg) and NCTD (2 mg/kg) were given together, the survival time was prolonged 1.6 times and 2 times as compared to the group treated by ELP alone or to non-treated controls, respectively. Moreover, the combined treatment gave more effective inhibition of hepatomegaly than ELP alone, suggesting that this protocol might have an organ-specific effect and might suppress the leukaemogenesis induced by FLV in some erythropoietic organs. These results indicate that a chemotherapeutic agent (ELP) associated with two immunomodulatory substances (NCTD and TCDO) is more effective than chemotherapy alone in controlling retroviral infection and in the prolongation of survival. These data taken together suggest that the role of the two immunomodulatory agents might be to suppress the retroviral infection synergistically with ELP and enhance immune functions. Possible modes of action are discussed and are under investigation.

Adjuvants, Immunologic↗

Enhanced production of interleukin 1 by mouse peritoneal macrophages after aclacinomycin administration.

The peritoneal cells of mice injected with aclacinomycin (ACM), an oncostatic drug of the anthracyclin family, were found to secrete more interleukin (IL-1), after two successive 24-h periods of in vitro LPS stimulation than those of control mice. This measured IL-1 production is one of the signs of enhanced macrophage activity. The cells of ACM-injected mice also contained more intracellular IL-1 than those of controls. In contrast, macrophages from ACM-injected mice only increased their IL-1 production after the first 24-h incubation with PMA, and not after the second 24-h incubation. The response to ACM was dose- and time-dependent. We have also compared the IL-1 production by macrophages from mice injected with other anthracyclins, at doses equimolar to that of 4 mg/kg ACM and we have observed that adriamycin, 4'-epiadriamycin and aclacinomycin had similar activity, while THP-adriamycin an daunorubicine were slightly more active. Exploitation of this increased IL-1 production by macrophages could be beneficial in the design of tumor treatment protocols.

Aclarubicin↗

Solution conformation of the type I collagen alpha-2 chain telopeptides studied by 1H and 13C NMR spectroscopy.

The high-field 1H and 13C NMR studies of the N- and C-terminal telopeptides of the alpha-2 chain of collagen were carried out in CD3OH/H2O solutions. All proton assignments are based on two-dimensional phase-sensitive COSY and ROESY experiments. The conformation of the N-telopeptide (nonamer) is predominantly extended with a small proportion of the molecules existing in a type I beta turn. The four residues involved in this turn are D3-A4-K5-G6 which is stabilized by a C = O(D3)-NH(G6) hydrogen bond. The C-terminal telopeptide is extended throughout. A model is proposed involving charge-charge and hydrophobic interactions between the extended alpha-2 chain N-telopeptide and the adjacent segments of triple-helix. A similar model is proposed for the C-telopeptide.

Amino Acid Sequence↗

A retrospective study on diagnosis and treatment of severe acute pancreatitis.

Severe acute pancreatitis is highly controversial on its diagnostic criteria, the optimum time for surgery, the selection of surgical procedures, and the prevention and treatment of complications. We treated 40 patients with severe acute pancreatitis from July 1983 to July 1988. The comparison of clinical and laboratory data of severe acute pancreatitis and mild acute pancreatitis showed that in some patients neither Ranson's nor Bank's criteria are reliable in classifying or predicting the severity of the disease. The coexistence of acute peritonitis and bloody ascites with elevated amylase level is very helpful to identify the local conditions of pancreatic necrosis and hemorrhage. We suggest early operation (within 48 hours) be applied in severe acute pancreatitis. In our series, five types of surgical procedures were used. We consider that proper treatment of acute respiratory distress syndrome (ARDS) is most important in the management of severe pancreatitis.

Abscess↗

The Cox proportional hazards model with change point: an epidemiologic application.

In this paper, we develop the Cox proportional hazards model with special structured time-dependent covariates in the context of prospective epidemiologic studies. Our model possesses the following two features: (i) different relative risk parameters are allowed for early versus late onset of the disease of interest; (ii) an additional parameter is introduced so that specification is not required for the time (age) at which a change of the magnitude of the relative risks takes place, the so-called change point. Some difficulties with statistical inference for the proposed model are briefly discussed, and the large-sample distribution of a test for no change point is derived. As an illustration, we apply the model to a set of data gathered on a group of white male medical students of The Johns Hopkins Medical School enrolled between 1948 and 1964. We examine the hypothesis that the effect of reactivity to the cold pressor test may vary with early versus late onset of hypertension.

Biometry↗

Enhanced activity of peritoneal cells after aclacinomycin injection: effect of pretreatment with superoxide dismutase on aclacinomycin-induced cytological alterations and antitumoral activity.

Peritoneal macrophages from mice injected with aclacinomycin (ACM) (4 mg/kg, i.p.) showed increased functional activity, as assessed by increased antitumoral activity in vitro and in vivo and zymosan-triggered chemoluminescence. They also showed ultrastructural signs of activation (increased number of cytoplasmic organelles), and atypical alterations (giant vacuoles and giant lysosomes containing heterogenous myelinoid bodies, lipofuscine-like substance, cytoplasmic debris, and a fine granular material). As these atypical alterations could be due to the generation of superoxide following ACM injection, superoxide dismutase (SOD) was injected 1 h prior to ACM administration. Neither the morphological characteristics of activation, nor the enhanced metabolic and antitumoral activities induced by ACM were affected by SOD pretreatment, but the atypical alterations were inhibited in a dose-dependent manner. Heat-inactivated SOD did not prevent their appearance. The atypical alterations were not found in peritoneal macrophages from talc or lipopolysaccharide-injected mice, but they were present in Adriamycin-treated mice and were also prevented by SOD pretreatment, indicating that the alterations are due to anthracycline treatment. Finally, [125I]SOD was phagocytized by peritoneal macrophages in vitro and in vivo and not by L1210 tumoral cells, explaining why the atypical alterations induced by ACM were no longer seen after SOD pretreatment. The unchanged direct oncostatic activity of ACM following SOD pretreatment suggests that this combination may have some wider perhaps clinical, potential.

Aclarubicin↗

Nonesterified fatty acids modulate steroidogenesis in mouse Leydig cells.

The effects of nonesterified fatty acids (NEFA) in modulating testosterone synthesis stimulated by luteinizing hormone (LH, 10 ng/sample) were investigated in isolated adult mouse Leydig cells. LH-stimulated testosterone production was inhibited by triglycerides (0-500 mg/dl, 50 mg/dl, 94% of the control and 500 mg/dl, 40%) and by a mixture of NEFA (100 microM, 70% of control, 200 microM, 54%, and greater than 200 microM, less than 50%). Oleic acid was a more potent inhibitor than linoleic, stearic, or palmitic acids. 8-Bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP, 5 mM) stimulated testosterone production comparable to LH but failed to reverse the inhibition of steroidogenesis produced by the NEFA. The inhibition produced by NEFA was dependent on extracellular Ca2+; and a Ca2+ channel antagonist, verapamil (10 microM), enhanced the inhibition of chylomicrons and fatty acids. 22(R)-hydroxycholesterol (10 microM) reversed the inhibition produced by NEFA. The inhibitory effects of NEFA were reversible by removal of the fatty acids. The results indicate that NEFA are potent modulators of testosterone synthesis in Leydig cells stimulated with either LH, cAMP, or intracellular Ca2+. NEFA inhibit steroidogenesis at one of the steps preceding conversion of cholesterol to pregnenolone.

8-Bromo Cyclic Adenosine Monophosphate↗

A 1H and 13C NMR study on the role of salt-bridges in the formation of a type I beta-turn in N-acetyl-L-Asp-L-Glu-L-Lys-L-Ser-NH2.

The conformation of the tetrapeptide N-Acetyl-Asp7-Glu8-Lys9-Ser10-NH2, a fragment of the type I collagen alpha-1 chain N-telopeptide, has been studied by 1H and 13C NMR and circular dichroism spectroscopy. The spectroscopic evidence, based on two-dimensional, phase-sensitive NMR techniques such as COSY, ROESY, proton-carbon shift correlation and selective COLOC, indicates a strong dependence of the conformation on the experimental conditions. In CD3OH/H2O (60/40) at ca. neutral pH the tetrapeptide forms a beta-turn, stabilized by a hydrogen bond between NH(S10) and CO(D7) and a strong salt-bridge between COO-(E8) and NH3+(K9). The beta-turn is type I and appears to coexist with a non-hydrogen-bonded structure. The coexistence of these two conformers is proven by proton NMR data such as NH-NH ROEs, reduced NH-H alpha (E8) coupling constant, NH(E8) low-field shift and the temperature coefficient of NH(S10), whereas the conclusion regarding the salt-bridge is based on 13C results. In the same solvent, at a pH below the pKa of the carboxyl groups, no evidence for a conformation other than extended can be found. In aqueous solution at approximately neutral pH, evidence for the E8-K9 charge interaction is observed, but not for a hydrogen bond anywhere in the molecule.

Amino Acid Sequence↗

[Clinical differential diagnosis of depressive neurosis and neurasthenia].

This article reported diagnostic findings in application of Chinese diagnostic criteria of neurosis published by Chinese Journal of Neurology and Psychiatry (1986; 19: 318-321) to a series of neurotic patients. 66 cases and 50 cases were met criteria of depressive neurosis and neurasthenia respectively. Two groups were compared. The results revealed some similarities and a lot of differences between these two disorders. According to clinical features authors proposed main points of differential diagnosis between these two disorders.

Adolescent↗

Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate.

We have recently observed that cigarette smoking affects plasma androgen concentrations. The effects of nicotine and cotinine, two products of cigarette smoking, on testosterone metabolism were determined. The activity of delta 4 steroid 5 alpha-reductase, which converts testosterone to 5 alpha-dihydrotestosterone (DHT) was measured in isolated dog prostate nuclei using testosterone (0-200 nM) as substrate and NADPH as cofactor. Activity of 3 alpha-hydroxysteroid dehydrogenase (HSD), which converts DHT to 3 alpha-androstanediol (3 alpha-diol) and is a reversible enzyme, was measured in isolated dog prostate microsomes with DHT (0-20 microM) as substrate and NADPH as cofactor. When microsomal fractions were incubated for 1 hour with and without nicotine (0-50 microM) and cotinine (0-100 microM), enzyme activity of HSD was significantly suppressed (p less than 0.001). The Vmax was not affected significantly (p greater than 0.60) and Km increased with increasing concentrations of nicotine and cotinine (p less than 0.05). Both nicotine and cotinine are competitive inhibitors of HSD in dog prostate microsomes with Ki's of 61 and 89 microM, respectively. The apparent 5 alpha-reductase activity was unaffected by nicotine and cotinine. The inhibitors produced a marked effect on activity of HSD when used in concentrations achieved in humans who smoke cigarettes. The results suggest that nicotine and cotinine are competitive inhibitors of the HSD, an important enzyme involved in the metabolism of DHT and produce an accumulation of DHT. These products of cigarette smoking could alter androgen action in tissue such as skin and prostate.

3-Hydroxysteroid Dehydrogenases↗