Phase Behaviors of Charged Macromolecules in Aqueous Solutions

Compared to the charge–charge interaction, the role of the dipole-dipole interaction has long been ignored in the phase behaviors of charged macromolecules in solutions. Charged macromolecules in solutions exhibit rich phase behaviors due to their complexity and they have been studied extensively. Phase separation can happen for charged macromolecules in the presence of monovalent salt, multivalent salt, and oppositely charged polymers, surfactants, etc., and for more advanced charged macromolecules such as polyzwitterions and polyampholytes, the phase diagram is even richer. In this perspective, the unacknowledged role of dipole-dipole interaction in the phase behaviors of charged macromolecular solutions will be introduced. Dipolar polymers can form complex, self-regulating structures which can be employed in various fields from drug-delivery systems to next-generation polymers. More importantly, it will shed light on how some of the life's basic and coherent structures such as biomolecular condensates and membrane-less organelles are assembled and built by charged biomacromolecules such as DNA, RNA, and proteins.     

The effect of TGFβ1 on murine tumor growth following direct intratumoral injection of plasmid DNA

In order to investigate TGFβ1 gene expression and its effect on murine tumor growth following direct intratumoral injection of naked plasmid DNA encoding human TGFβ1, LM₃ murine lung adenocarcinoma cells were inoculated subcutaneously to T₇₃₉ mice and grew to tumor nodules in 2 weeks. Multiple direct intratumoral injection of plasmid DNA, PMAMneo- TGFβ1, were given and compared with saline or vector plasmid administration groups. The growth of tumor was observed till the 8th week when the mice were killed for Northern blot analysis and histopathological study of tumoral tissue. The results showed that the growth of tumor was boosted in the TGFβ1 gene treated mice as compared with the control groups, whereas there was no significant difference in the metastatic behavior. Northern blot showed efficient expression of TGFβ1 mRNA in the treated group. The present study indicated that TGFβ1 may stimulate tumor growthin vivo through certain mechanisms. And direct intra-tumoral injection of nude plasmid DNA may be a promising gene transfer strategyin vivo. This work was supported by the National Natural Science Foundation of China (No. 39370761).     

Enhanced survival of glioma bearing rats following boron neutron capture therapy with blood-brain barrier disruption and intracarotid injection of boronophenylalanine

Boronophenylalanine (BPA) has been used for boron neutron capture therapy (BNCT) of brain tumors in both experimental animals and humans. The purpose of the present study was to determine if the efficacy of BNCT could be enhanced by means of intracarotid (i.c.) injection of BPA with or without blood-brain barrier disruption (BBB-D) and neutron irradiation using a rat brain tumor model. For biodistribution studies, F98 glioma cells were implanted stereotactically into the brains of Fischer rats, and12 days later BBB-D was carried out by i.c. infusion of 25% mannitol (1.373 mOsmol/ml), followed immediately by i.c. administration of 300, 500 or 800 mg of BPA/kg body weight (b.w.). At the 500 mg dose a fourfold increase in tumor boron concentration (94.5 g/g) was seen at 2.5 hours after BBB-D, compared to 20.8 g/g in i.v. injected animals. The best composite tumor to normal tissue ratios were observed at 2.5 hours after BBB-D, at which time the tumor: blood (T: Bl) ratio was10.9, and the tumor: brain (T: Br) ratio was 7.5, compared to 3.2 and 5.0 respectively for i.v. injected rats. In contrast, animals that had received i.c. BPA without BBB-D had T: Bl and T: Br ratios of 8.5 and 5.9, respectively, and the tumor boron concentration was 42.7g/g. For therapy experiments, initiated 14 days after intracerebral implantation of F98 glioma cells, 500 mg/kg b.w. of BPA were administered i.v. or i.c. with or without BBB-D, and the animals were irradiated 2.5 hourslater at the Brookhaven Medical Research Reactor with a collimated beam of thermal neutrons delivered to the head. The mean survival time for untreated control rats was 24 ± 3 days, 30 ± 2 days for irradiated controls, 37 ± 3 days for those receiving i.v. BPA, 52 ± 15 days for rats receiving i.c. BPA without BBB-D, and 95 ± 95 days for BBB-D followed by i.c. BPA and BNCT. The latter group had a 246% increase in life span (ILS) compared to untreated controls and a 124% ILS compared to that of i.v. injected animals. These survival data are the best ever obtained with the F98 glioma model and suggest that i.c. administration of BPA with or without BBB-D may be useful as a means to increase the efficacy of BNCT.     

Inhibition of telomerase activity correlates with a decrease in the RNA component of telomerase during differentiation

In most normal somatic cells the telomeres of human chromosomes shorten with each cell division because of low expression or lack of telomerase activity. Telomerase, a ribonucleoprotein that synthesizes telomeric DNA onto chromosomal ends, is reactivated or upregulated in tumor cells and maintains the stability of telomere length. We previously showed that treatment of HL60 leukemia cells with differentiation-inducing agents resulted in inhibition of telomerase activity. In the present study, we found that the decrease in telomerase activity did not temporally correlate with the expression of a differentiation marker, CD11b, on the cell surface. Mixing of protein extracts from telomerase-negative differentiated HL60 cells with those from parental HL60 cells did not result in inhibition of telomerase activity, suggesting that a diffusible cellular telomerase inhibitor was not produced in the differentiated cells. However, a decrease in telomerase activity correlated with a selective decrease of telomerase RNA expression, a decrease in the levels of total cellular RNA, and an increase in cells at G(0) phase.     

Increasing nosocomial infections of methicillin-resistant Staphylococcus aureus at a teaching hospital in Taiwan

Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide important pathogen in nosocomial infections. To investigate the extent of the problem in Taiwan, analysis for the period of 1981-1994 was carried out of prospective surveillance data from the National Taiwan University Hospital, a major university teaching hospital in Taiwan. The number of nosocomial MRSA infections increased from five in 1981 to 133 in 1994, and the incidence increased from 0.2 episodes/1000 discharges in 1981 to 2.9 episodes/1000 discharges in 1994. The most common infection site was surgical wounds, which accounted for 26.3% of total 577 episodes of nosocomial MRSA infections during the study period. However, bacteraemia has become more and more common during the past 14 years. MRSA infections occured more frequently in patients stayed in the burn unit and other intensive care units than in the general wards. Other than oxacillin, the resistance rate to many other antibiotics also increased in S. aureus strains causing nosocomial infections in this hospital. Vancomycin remained active to all these S. aureus strains, even until 1994.     

Recurrence after resection ofα-fetoprotein-positive hepatocellular carcinoma

The long-term prognosis of surgery for hepatocellular carcinoma (HCC) is not yet satisfactory, the main reason being the high recurrence rate. The authors report the results of a long-term follow-up of 308 patients with HCC who became -fetoprotein-(AFP)-negative after resection between 1975 and 1991. By March 1992, there was recurrence in 134 patients (43.5%). The 1-, 3-, 5- and 10-year recurrence rates were 9.2%, 38.8%, 54.9% and 85.0%, respectively. The 5-year survival rate was 49.7% for patients who had undergone a second hepatic resection (n=48). Analysis of factors influencing postoperative recurrence indicated that patients subjected to mass survey, with a lower -glutamyltransferase level, at an early stage of TNM classification, with a tumour of less than 5 cm, without tumour embolus, and with postoperative immunotherapy had a lower incidence of recurrence. It is concluded that the earlier the disease is diagnosed, the less the recurrence rate; adjuvant immunotherapy may reduce postoperative recurrence, and the early detection and resection of a recurrent tumour are important to prolonging survival further after curative resection of HCC.Abbreviations HCC hepatocellular carcinoma - AFP -fetoprotein - HBsAg hepatitis B surface antigen Presented in part at the 4th Wilson T. S. Wang International Surgical Symposium, 11–13 December 1992, Hong Kong.     

Release of [3H]5-hydroxytryptamine from the intermediate area of rat thoracic spinal cord is modulated by presynaptic autoreceptors

Serotonin (5-HT) nerve terminals innervate sympathetic preganglionic neurons of the intermediolateral cell column (IML); however, neither the depolarization-induced release of 5-HT nor the presence of presynaptic modulatory autoreceptors have been directly studied in this system. We used in vitro superfusion of the microdissected intermediate area (including the intermediolateral cell column, intercalated nucleus, and central autonomic nucleus) of the rat thoracic spinal cord to measure basal and stimulated release of preloaded [³H]5-HT. Elevated K⁺ evoked a concentration- and Ca²⁺ dependent release of [³H]5-HT. Exogenous 5-HT and the 5-HT_1B agonist, CGS-12066B, both decreased the K⁺-stimulated release of [³H]5-HT. A 5-HT_1B antagonist (methiothepin) blocked the 5-HT- and the CGS-12066B-induced inhibition of K⁺-evoked release of [³H]5-HT. A 5-HT_1A antagonist (NAN-190) did not alter the inhibitory actions of exogenous 5-HT. Moreover, a 5-HT_1A agonist (8-OH-DPAT), a 5-HT_2A/2C agonist [(+/-)-DOI hydrochloride], and a 5-HT₃ agonist (2-methyl-5-HT) did not alter the K⁺ evoked release of [³H]5-HT. These data demonstrate that 5-HT is released from the intermediate area of the rat thoracic spinal cord. The 5-HT receptor subtype involved in the inhibition of the evoked release of [³H]5-HT is of the 5-HT_1B subtype. These findings may help clarify the complex role of 5-HT in spinal regulation of the sympathetic nervous system. © 1994 Wiley-Liss, Inc

1 This article is US Government work and, as such, is in the public domain in the United States of America.

     

流行性出血热患者早期免疫应答的研究

应用反向被动血凝集抑制试验和血凝集抑制试验检测流行性出血热患者早期血清（７病日内）中病毒核蛋白、膜蛋白抗体。１０３例患者血清,仅核蛋白抗体出现者３３例,病情转径及无变化者３１例（９３．９４％）．而转重者仅２例（６．０６％）,且其血清抗体主要为ＩｇＧ型。仅膜蛋白抗体出现的患者９例,病情转重者８例（８８．８９％）,其抗体主要为ＩｇＭ．核蛋白、膜蛋白抗体均阳性的６１例患者,病情转归介于上述二者之间．提示：核蛋白抗体先出现的患者,病情多转轻,而膜蛋白抗体先出现的患者,病情普遍转重,似与病毒的＂一次性打击＂有关。在仅核蛋白抗体出现的患者中,有２例病情转重,但其抗体球蛋白类型为ＩｇＧ,故尚不能排除本病有＂二次感染＂的可能,这一现象在推行本病预防接种时值得重视,另对进一步探讨本病的发病机理及预测患者的病情转归亦具参考价值。     

“小粘膜”型胃癌诊断的探讨

所谓“小粘膜”型胃癌系指病灶直径小于４ｃｍ,局限于粘膜层或仅有轻度粘膜下层侵犯的早期胃癌。本文总结经内镜发现并得到手术、病理证实的“小粘膜”型胃癌１２例,着重对期诊断问题作一探讨。