Volumetric Analysis of Gallbladder in Extremely Premature Infants

Background

We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants.

In vitro growth suppression and morphological change in a human renal cell carcinoma cell line by the introduction of normal chromosome 3 via microcell fusion

Cytogenetic and molecular studies of human renal cell carcinoma (RCC) have suggested that the genetic and functional losses of one or more putative tumor suppressor genes on the short arm of chromosome 3 play a crucial role in the development of this disease. To examine whether the introduction of chromosome 3 has any effects on the biology of RCC cells, we introduced either chromosome 3, 7, or 11 from normal human fibroblasts into a newly established human RCC cell line with loss of heterozygosity for 3p, via microcell-mediated chromosome transfer. Microcell hybrids containing an introduced, intact chromosome 3 showed a significant reduction in in vitro growth rate and saturation density together with morphological alteration; these properties were not altered in microcell hybrids containing an introduced chromosome 7 or 11. During long-term cultivation, one of the clones that had lost the introduced chromosome 3 showed growth properties and morphology similar to those of the parental cell lines. Thus, our findings provide additional evidence for the presence of a putative tumor suppressor gene or genes on normal chromosome 3p and indicate that the gene is a dominant, negative growth regulator whose loss promotes progressive features of the neoplastic phenotype. © 1994 Wiley-Liss, Inc.     

Suppression of experimental autoimmune uveoretinitis by anti-alphabeta TCR monoclonal antibody

PURPOSE: To evaluate the effects of anti-alphabeta T cell receptor monoclonal antibody (R73) on the induction of experimental autoimmune uveoretinitis (EAU) in rats. METHODS: Lewis rats in which EAU was induced were treated with R73. All rats were examined for the clinical course of EAU, pathological findings of the globe, delayed-type hypersensitivity, and the interleukin-2 (IL-2) gene and protein expression in the eye. RESULTS: The R73 treatment was effective for delaying EAU onset, decreasing the severity of EAU, and suppressing delayed-type hypersensitivity to the antigen. IL-2 gene and protein expression was reduced by R73 treatment in the anterior and posterior segments of the eye. CONCLUSION: R73 treatment is effective for suppression of the development of EAU, inhibiting IL-2 expression in the eye.     

Smokers lack morning increase in platelet sensitivity to nitric oxide

This study investigated whether a circadian variation is present in the sensitivity of platelets to nitric oxide (NO) and, if so, if long-term smoking modifies it. Blood samples were taken at 0:00, 6:00, 9:00, 12:00, and 18:00 from 14 nonsmokers and 10 smokers. Dose-response curves for platelet aggregation by collagen were constructed in both the presence and absence of 1.0 micro M of NOR-3, a NO donor. The antiaggregation properties of NOR-3 were quantified by the half maximal concentration (EC50) ratio in the presence of NOR-3 to that in its absence. Platelet aggregation showed a monophasic circadian rhythm, with the lowest levels at 6:00 and the highest at 18:00 in both groups. However, there was a significant (p < 0.01) upward shifting of platelet aggregation in the smokers. A circadian variation in sensitivity to NOR-3 also was demonstrated in the nonsmokers. The sensitivity was lowest at 6:00 (1.68 +/- 0.19), increased significantly at 9:00 (2.58 +/- 0.26; p < 0.01), and remained high at 12:00 (2.47 +/- 0.21; p < 0.05). In smokers, however, a circadian variation in platelet sensitivity to NOR-3 was not found. Furthermore, the sensitivity was significantly lower at 9:00 and 12:00 in smokers (1.94 +/- 0.26 and 1.76 +/- 0.13, respectively; p < 0.05 for both) than in nonsmokers. Thus, long-term smoking impairs the normal morning increase in platelet sensitivity to NO, making platelets in smokers more thrombogenic during the hazardous hours.     

Prolyl endopeptidase inhibitors from the roots of Lindera strychnifolia F. Vill

Prolyl endopeptidase (PEP, EC 3.4.21.26) has been proposed to play a role in degradation of proline-containing neuropeptides involved in the processes of learning and memory, e.g., vasopressin, substance P, and thyrotropin-releasing hormone (TRH). In the course of our search for bioactive constituents in medicinal plants, we studied the PEP inhibitory constituents of the roots of Lindera strychnifolia F. VILL and isolated two known tannins, epicatechin (1) and aesculitannin B (2), and four known sesquiterpenes, linderene (3), linderene acetate (4), linderalactone (5) and isolinderalactone (6) as inhibitors. On the inhibitory activities of six compounds against PEP from Flavobacterium meningosepticum and that from rat brain supernatant, compounds 1, 2 and 4 inhibited the enzyme from Flavobacterium more strongly than that from rat brain supernatant. However, compounds 3, 5 and 6 inhibited the enzymes from both origins to the same extent and furthermore, compound 6 was the strongest natural inhibitor against PEP from rat brain supernatant. The kinetic study of these inhibitors indicated that compounds 1, 2 are noncompetitive inhibitors and compounds 3-6 are competitive inhibitors. This is the first example of non-phenolic constituents showing significant competitive inhibitory activity being isolated from natural medicines.     

Extracellular magnesium ion modifies the actions of volatile anesthetics in area CA1 of rat hippocampus in vitro

BACKGROUND: Magnesium ion (Mg2+) is involved in important processes as modulation of ion channels, receptors, neurotransmitter release, and cell excitability in the central nervous system. Although extracellular Mg2+ concentration ([Mg2+]o) can be altered during general anesthesia, there has been no evidence for [Mg2+]o-dependent modification of anesthetic actions on neural excitability in central nervous system preparations. The purpose of current study was to determine whether the effects of volatile anesthetics are [Mg2+]o-dependent in mammalian central nervous system. METHODS: Extracellular electrophysiologic recordings from CA1 neurons in rat hippocampal slices were used to investigate the effects of [Mg2+]o and anesthetics on population spike amplitude and excitatory postsynaptic potential slope. RESULTS: The depression of population spike amplitudes and excitatory postsynaptic potential slopes by volatile anesthetics were significantly dependent on [Mg2+]o. The effects were attenuated in the presence of a constant [Mg2+]o/extracellular Ca2+ concentration ratio. However, neither N-methyl-d-aspartate receptor antagonists nor a non-N-methyl-d-aspartate receptor antagonist altered the [Mg2+]o-dependent anesthetic-induced depression of population spikes. Volatile anesthetics produced minimal effects on input-output (excitatory postsynaptic potential-population spike) relations or the threshold for population spike generation. The effects were not modified by changes in [Mg2+]o. In addition, the population spike amplitudes, elicited via antidromic (nonsynaptic) stimulation, were not influenced by [Mg2+]o in the presence of volatile anesthetics. CONCLUSIONS: These results provide support that alteration of [Mg2+]o modifies the actions of volatile anesthetics on synaptic transmission and that the effects could be, at least in part, a result of presynaptic Ca2+ channel-related mechanisms.     

Role of oxidative DNA damage caused by carbon tetrachloride-induced liver injury -- enhancement of MeIQ-induced glutathione S-transferase placental form-positive foci in rats

The strong association between chronic inflammation and development of cancer is well-established in chronic inflammatory states. Nitric oxide (NO) is generated by inflammatory cytokines due to the action of inducible nitric oxide (iNOS), oxidizing DNA to form 8-hydroxy-2'-deoxyguanosine (8-OHdG) adducts, a major species of oxidative DNA damage. In the present study, we investigated the enhancing effect of carbon tetrachloride, a typical hepatotoxic chemical, on rat 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) hepato-carcinogenesis. A total of 420, 21-day-old, male Fisher 344 rats were given MeIQx at a concentration of 0, 0.001 ppm (human exposure level), 0.01, 0.1, 1, 10 and 100 ppm in the diet, and each group was separated into carbon tetrachloride-treated and vehicle-treated subgroups. Carbon tetrachloride was given by subcutaneous (s.c.) injection twice a week at a dose of 0.125 ml/kg body weight (b.w.) for the first 10 weeks and then at 0.25 ml/kg b.w. during the next 10 weeks. All rats were sacrificed at the end of week 22. In the vehicle-treated animals, only 100 ppm MeIQx significantly increased the number of glutathione S-transferase placental form (GST-P)-positive foci in the liver compared with 0 ppm MeIQx. Co-administration of carbon tetrachloride enhanced the induction of GST-P-positive foci by MeIQx in each group and the curve was almost the same pattern as that of vehicle-treated group but their numbers were significantly enhanced with 10 ppm and above compared with 0 ppm MeIQx. Persistent liver injury and liver cell proliferation were histopathologically observed in carbon tetrachloride-treated groups. Increase of 8-hydroxydeoxyguanosine (8-OHdG) formation and iNOS overexpression were observed by co-administration of carbon tetrachloride in MeIQx-treated rat liver. Our results indicate that carbon tetrachloride enhances MeIQx hepato-carcinogenicity through increase in oxidative DNA damage but non-effect levels of MeIQx carcinogenic activity still exist.     

Enhanced expression of thymidylate synthase mediates resistance of uterine cervical cancer cells to radiation

It has been shown that there is an inverse relationship between the level of thymidylate synthase (TS) and therapeutic outcomes in patients with malignancies including cervical cancer. To clarify the mechanism of the poor prognosis of cervical cancer with high TS expression, we introduced TS cDNA to the human uterine cervical cancer cell line SKG-II and evaluated the effect of TS expression on its radiosensitivity. After selection, stable transformants of SKG-II cells expressing high level of TS (SKG-II/TS) and control cells (SKG-II/luciferase) were obtained. The level of TS measured by the FdUMP-TS binding assay was significantly higher (p < 0.05) in SKG-II/TS than in control (2.0 +/- 0.1 and 1.3 +/- 0.1 pmol/mg, respectively). No difference was observed in in vitro cell growth or in vivo tumor growth. On evaluation of in vitro radiosensitivity, the 50% growth inhibitory dose (ID(50)) was 3.1 +/- 0.1 Gy in SKG-II/TS and was significantly higher (p < 0.01) than that in control (2.2 +/- 0.1 Gy). From these results, it is suggested that one of the reasons of poor outcome of cervical cancer to radiation is high TS expression.