A sustained high-temperature fusion plasma regime facilitated by fast ions.

Nuclear fusion is one of the most attractive alternatives to carbon-dependent energy sources1. Harnessing energy from nuclear fusion in a large reactor scale, however, still presents many scientific challenges despite the many years of research and steady advances in magnetic confinement approaches. State-of-the-art magnetic fusion devices cannot yet achieve a sustainable fusion performance, which requires a high temperature above 100 million kelvin and sufficient control of instabilities to ensure steady-state operation on the order of tens of seconds2,3. Here we report experiments at the Korea Superconducting Tokamak Advanced Research4 device producing a plasma fusion regime that satisfies most of the above requirements: thanks to abundant fast ions stabilizing the core plasma turbulence, we generate plasmas at a temperature of 100 million kelvin lasting up to 20 seconds without plasma edge instabilities or impurity accumulation. A low plasma density combined with a moderate input power for operation is key to establishing this regime by preserving a high fraction of fast ions. This regime is rarely subject to disruption and can be sustained reliably even without a sophisticated control, and thus represents a promising path towards commercial fusion reactors.

Nonambipolar Transport due to Electrons with 3D Resistive Response in the KSTAR Tokamak.

A small nonaxisymmetric (3D) magnetic field can induce nonambipolar transport of the particle species confined in a tokamak and thus a significant change of plasma rotation. This process can be in a favor of instability control in the region where the tokamak plasma is sufficiently collisional and resistive, as observed in the applications of n=1 resonant magnetic perturbations to the KSTAR tokamak. The plasma rotation can be globally accelerated due to radially drifting electrons and constrained to the electron root, if the radial transport is enhanced by an amplified 3D response. This mechanism is verified by a kinetically self-consistent magnetohydrodynamic modeling for both response and transport, which offers the quantitative explanations on the internal n=1 structure detected by electron-cyclotron-emission imaging and the cocurrent plasma spinning observed in the experiments.

The impact of hepatitis B virus infection and vaccination on the development of non-Hodgkin lymphoma.

Hepatitis B virus (HBV) infection has been documented as a risk factor for non-Hodgkin lymphoma (NHL). However, there are few large cohort studies, and there is no report about the impact of HBV vaccination. We conducted this study to evaluate these issues. We used the nationwide cohort of the Taiwan National Health Insurance Research Database for 1997-2013. We compared the incidence and the risk of developing NHL and CD20+ aggressive lymphoma between HBV and non-HBV cohorts. The hazard ratios (HRs) were computed using Cox proportional hazards models. We matched these two large cohorts to reconfirm the data. We also compared the incidence of NHL between cohorts born before and after the inception of universal HBV vaccination. We found that HBV infection increased the risk for developing NHL and CD20+ aggressive lymphoma, with HRs of 4.14 and 5.52, with a higher incidence of 17.07 and 13.9 per 100 000 person-years, respectively, compared to the non-HBV cohort. The incidence of NHL in the cohort born in the era before universal HBV vaccination was higher with 1.85 per 100 000 person-years compared to 0.74 in the cohort born later aged younger than 20. Our study confirms that HBV confers a greater risk for developing NHL, especially CD20+ aggressive lymphoma. The impact of HBV vaccination is protective against lymphoma development in the teenagers in an endemic area, but longer follow-up is needed for older age.

Solid nanoemulsion as antigen and immunopotentiator carrier for transcutaneous immunization.

Imiquimod, a toll-like receptor 7 (TLR7) agonist, is an active pharmaceutical ingredient (API) established for the topical treatment of several dermal cancerous and precancerous skin lesions. Within this work, the immunostimulatory effect of imiquimod is further exploited in a transcutaneous immunization (TCI) approach based on a solid nanoemulsion (SN) formulation. SN contains a combination of imiquimod with the model peptide antigen SIINFEKL as a novel approach to omit needle and syringe and optimize dermal antigen administration. Excipients including sucrose fatty acid esters and the pharmaceutically acceptable oils MCT (middle chain triglycerides), avocado oil, jojoba wax and squalene are high pressure homogenized together with the antigen SIINFEKL. Freeze drying was performed to eliminate water and to achieve spreadable properties of the formulation for dermal administration. The influence of the different oil components was assessed regarding in vitro drug permeation in a Franz diffusion cell model using a murine skin setup. In vivo performance in terms of cytotoxic T-cell response was assessed in a C57BL/6 mouse model. Whereas Aldara® cream contains imiquimod in a dissolved state, the SN formulations carry the active in a suspended state. This resulted in a reduction of imiquimod permeation across murine skin from the SN when compared to Aldara® cream. In spite of this permeation rate reduction, each SN induced an in vivo immune response by specific T-cell lysis. A stabilized solid nanosuspension containing squalene/tocopherol exhibited a significantly higher performance (p⩽0.05) in comparison with Aldara® cream. MCT based SN exerted an in vivo effect comparable to Aldara®. In conclusion, anhydrous highly dispersed vehicles containing imiquimod in a submicron particle size distribution can represent promising formulations for TCI. The choice of the oil component has a strong influence on SN performance, independent of in vitro drug permeation.

A KRAS mutation status-stratified randomized phase II trial of gemcitabine and oxaliplatin alone or in combination with cetuximab in advanced biliary tract cancer.

BACKGROUND: Previous clinical trials have not proved that adding epidermal growth factor receptor inhibitors to chemotherapy confers a survival benefit for patients with advanced biliary tract cancer (ABTC). Whether the KRAS mutation status of tumor cells confounded the results of past studies is unknown. PATIENTS AND METHODS: ABTC patients stratified by KRAS status, Eastern Cooperative Oncology Group performance status, and primary tumor location were randomized 1 : 1 to receive GEMOX (800 mg/m(2) gemcitabine and 85 mg/m(2) oxaliplatin) or C-GEMOX (500 mg/m(2) cetuximab plus GEMOX) every 2 weeks. The primary end point was objective response rate (ORR). RESULTS: The study enrolled 122 patients between December 2010 and May 2012 (62 treated with C-GEMOX and 60 with GEMOX). Compared with GEMOX alone, C-GEMOX was associated with trend to better ORR (27% versus 15%; P = 0.12) and progression-free survival (PFS, 6.7 versus 4.1 months; P = 0.05), but not overall survival (OS, 10.6 versus 9.8 months; P = 0.91). KRAS mutations, which were detected in 36% of tumor samples, did not affect the trends of difference in ORR and PFS between C-GEMOX and GEMOX. The two treatment arms had similar adverse events, except that more patients had skin rashes, allergic reactions, and neutropenia in the C-GEMOX arm. Of patients with C-GEMOX, the presence of a grade 2 or 3 skin rash was associated with significantly better ORR, PFS, and OS. CONCLUSIONS: Addition of cetuximab did not significantly improve the ORR of GEMOX chemotherapy in ABTC, although a trend of PFS improvement was observed. The trend of improvement did not correlate with KRAS mutation status. CLINICAL TRIALS NUMBER: This study is registered at ClinicalTrials.gov (NCT01267344). All patients gave written informed consent.

Position-controlled uniform GaAs nanowires on silicon using nanoimprint lithography.

We report on the epitaxial growth of large-area position-controlled self-catalyzed GaAs nanowires (NWs) directly on Si by molecular beam epitaxy (MBE). Nanohole patterns are defined in a SiO2 mask on 2 in. Si wafers using nanoimprint lithography (NIL) for the growth of positioned GaAs NWs. To optimize the yield of vertical NWs the MBE growth parameter space is tuned, including Ga predeposition time, Ga and As fluxes, growth temperature, and annealing treatment prior to NW growth. In addition, a non-negligible radial growth is observed with increasing growth time and is found to be independent of the As species (i.e., As2 or As4) and the growth temperatures studied. Cross-sectional transmission electron microscopy analysis of the GaAs NW/Si substrate heterointerface reveals an epitaxial growth where NW base fills the oxide hole opening and eventually extends over the oxide mask. These findings have important implications for NW-based device designs with axial and radial p-n junctions. Finally, NIL positioned GaAs/AlGaAs core-shell heterostructured NWs are grown on Si to study the optical properties of the NWs. Room-temperature photoluminescence spectroscopy of ensembles of as-grown core-shell NWs reveals uniform and high optical quality, as required for the subsequent device applications. The combination of NIL and MBE thereby demonstrates the successful heterogeneous integration of highly uniform GaAs NWs on Si, important for fabricating high throughput, large-area position-controlled NW arrays for various optoelectronic device applications.

Comparison of bacterial strains and antibiotic susceptibilities in urinary isolates of spinal cord injury patients from the community and hospital.

STUDY DESIGN: A one-year epidemiological survey. OBJECTIVE: To compare bacterial strains and antimicrobial susceptibilities of urinary isolates from hospital and community spinal cord injury (SCI) patients. SETTING: A specialized SCI unit in a freestanding rehabilitation hospital. METHODS: From June 2012 through May 2013, urine cultures were obtained from all of the newly admitted patients. Bacterial strains and antimicrobial susceptibilities were compared between patients from community and hospital settings. RESULTS: The proportion of Enterobacteriaceae in the total urinary isolates from hospital-dwelling patients was smaller than that from community-dwelling patients (66.0 vs. 85.5%, P<0.001), while the proportions of Pseudomonas, Acinetobacter and Enterococcus species were relatively larger (8.7%, 6.0% and 12.0% vs. 2.8%, 0.7% and 2.8%, respectively, P<0.05). The isolates from hospital-dwelling patients showed lower susceptibility to ampicillin, amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole and all generations of cephalosporin (P<0.05), and a higher prevalence of extended-spectrum beta-lactamase (ESBL)-producers (41.7 vs. 5.4%, P<0.001), compared with those from community-dwelling patients. The susceptibility rates to levofloxacin were lower than 50% in both community and hospital-dwelling patients. CONCLUSION: Broader-spectrum antibiotics should be considered in treating nosocomial urinary tract infection (UTI) of SCI patients because of the relatively wide variety of organisms and higher frequency of antibiotic-resistant strains, including ESBL-producing Enterobacteriaceae in hospital-derived specimens. Furthermore, in areas with high prevalence of fluoroquinolone resistance, fluoroquinolones should be used with caution during empirical treatment for UTI in SCI patients.

Rotational resonance of nonaxisymmetric magnetic braking in the KSTAR tokamak.

One of the important rotational resonances in nonaxisymmetric neoclassical transport has been experimentally validated in the KSTAR tokamak by applying highly nonresonant n=1 magnetic perturbations to rapidly rotating plasmas. These so-called bounce-harmonic resonances are expected to occur in the presence of magnetic braking perturbations when the toroidal rotation is fast enough to resonate with periodic parallel motions of trapped particles. The predicted and observed resonant peak along with the toroidal rotation implies that the toroidal rotation in tokamaks can be controlled naturally in favorable conditions to stability, using nonaxisymmetric magnetic perturbations.

Isolation and characterization of antifungal compound from Lactobacillus plantarum KCC-10 from forage silage with potential beneficial properties.

AIMS: The purpose of this study was to isolate, identify and characterize an antifungal compound from Lactobacillus plantarum KCC-10 from forage silage with potential beneficial properties. METHODS AND RESULTS: The 16S rRNA gene-based phylogenetic affiliation was determined using bioinformatic tools and identified as Lactobacillus sp. KCC-10 with 100% sequence similarity to L. plantarum. The antifungal substances were extracted with ethyl acetate from spent medium in which Lactobacillus sp. KCC-10 was cultivated. Antifungal activity was assessed using the broth microdilution technique. The compounds were obtained by eluting the crude extract with various concentrations of solvents followed by chromatographic purification. Based on the infrared, (13) C nuclear magnetic resonance (NMR) and (1) H NMR spectral data, the compound was identified as a phenolic-related antibiotic. The minimum inhibitory concentration of the compound against Aspergillus clavatus, A. oryzae, Botrytis elliptica and Scytalidium vaccinii was 2.5 mg ml(-1) and that against A. fumigatus, A. niger and S. fusca was 5.0 mg ml(-1) , respectively. In addition, Lactobacillus sp. KCC-10 was highly sensitive towards oxgall (0.3%) but grew well in the presence of sodium taurocholate (0.3%). An antimicrobial susceptibility pattern was an intrinsic feature of this strain; thus, consumption does not represent a health risk to humans or animals. CONCLUSION: Novel L. plantarum KCC-10 with antifungal and potential probiotic properties was characterized for use in animal food. SIGNIFICANCE AND IMPACT OF THE STUDY: This study revealed that L. plantarum KCC-10 exhibited good antifungal activity similar to that of probiotic Lactobacillus strains.

Appearance and dynamics of helical flux tubes under electron cyclotron resonance heating in the core of KSTAR plasmas.

Dual (or sometimes multiple) flux tubes (DFTs) have been observed in the core of sawtoothing KSTAR tokamak plasmas with electron cyclotron resonance heating. The time evolution of the flux tubes visualized by a 2D electron cyclotron emission imaging diagnostic typically consists of four distinctive phases: (1) growth of one flux tube out of multiple small flux tubes during the initial buildup period following a sawtooth crash, resulting in a single dominant flux tube along the m/n=1/1 helical magnetic field lines, (2) sudden rapid growth of another flux tube via a fast heat transfer from the first one, resulting in approximately identical DFTs, (3) coalescence of the two flux tubes into a single m/n=1/1 flux tube resembling the internal kink mode in the normal sawteeth, which is explained by a model of two current-carrying wires confined on a flux surface, and (4) fast localized crash of the merged flux tube similar to the standard sawtooth crash. The dynamics of the DFTs implies that the internal kink mode is not a unique prerequisite to the sawtooth crash, providing a new insight on the control of the sawtooth.

Suppression of edge localized modes in high-confinement KSTAR plasmas by nonaxisymmetric magnetic perturbations.

Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.

Effects of electron-cyclotron-resonance-heating-induced internal kink mode on the toroidal rotation in the KSTAR Tokamak.

It is observed that the magnitude of the toroidal rotation speed is reduced by the central electron cyclotron resonance heating (ECRH) regardless of the direction of the toroidal rotation. The magnetohydrodynamics activities generally appear with the rotation change due to ECRH. It is shown that the internal kink mode is induced by the central ECRH and breaks the toroidal symmetry. When the magnetohydrodynamics activities are present, the toroidal plasma viscosity is not negligible. The observed effects of ECRH on the toroidal plasma rotation are explained by the neoclassical toroidal viscosity in this Letter. It is found that the neoclassical toroidal viscosity torque caused by the internal kink mode damps the toroidal rotation.

Efficacy and safety of dose-modified docetaxel plus cisplatin-based induction chemotherapy in Asian patients with locally advanced head and neck cancer.

WHAT IS KNOWN AND OBJECTIVE: The beneficial effects of docetaxel plus cisplatin-based induction chemotherapy for patients with unresectable, advanced head and neck cancer (HNC) have been documented in Western countries. However, the efficacy of such treatment has not been confirmed in Asian patients. We aimed to determine whether incorporation of dose-modified docetaxel into a cisplatin-based induction regimen would be both effective and tolerable in our Asian population of patients. METHODS: Thirty-six patients with stage III or IV HNC who had undergone cisplatin-based induction chemotherapy were included in the current analysis. Fifty-three percentage of the patients had received induction chemotherapy with bolus cisplatin and continuous 5-fluorouracil (PF group), while the remaining 47% had additionally received dose-modified docetaxel (TPF group). We assessed the relative impact of the two treatments on clinical outcomes and treatment-related toxicities. RESULTS AND DISCUSSION: The disease control rate was higher in the TPF group (92·9% vs. 76·5%), although the difference did not reach statistical significance (P = 0·217). Addition of docetaxel increased the median progression-free survival to 435 days, which was 2·3 times longer than that (188 days) of patients not receiving docetaxel (P = 0·019). Non-haematological toxicity profile was similar and acceptable in both treatment groups. Higher incidence of grade 3/4 neutropenia and more episodes of neutropenic fever-related hospitalization occurred in the docetaxel-treated patients, but most of them were managed uneventfully. WHAT IS NEW AND CONCLUSION: Addition of dose-modified docetaxel to cisplatin-based induction chemotherapy was both efficacious and generally safe. Docetaxel addition significantly prolonged progression-free survival and had an acceptable safety profile in our Asian population of patients with locoregionally advanced HNC.

Anti-melanoma, tyrosinase inhibitory and anti-microbial activities of gold nanoparticles synthesized from aqueous leaf extracts of Teraxacum officinale.

There has been a tenacious search for pharmaceuticals of natural origin, as they are cost-effective and are noted for having little or no side effects. The rate at which diseases are developing resistance to synthetic drugs is quite alarming, and the side effects of these drugs remain an excruciating agony to the pharmaceutical industry. Gold nanoparticles (AuNPs) have wide applications in current technology. However, their use in medicine has not been adequately explored. Chemical methods for the synthesis are associated with environmental benignity and tissue toxicity on in vivo administration. For the first time, we have synthesized AuNPs from leaf extracts of Teraxacum officinale that were found to have significant anti-melanoma, tyrosinase inhibitory and anti-microbial effects, and hence stand as promising candidates for use in cosmetics medical and food industries.

pH-dependent perforation of macrophage phagosomes by listeriolysin O from Listeria monocytogenes.

The pore-forming toxin listeriolysin O (LLO) is a major virulence factor implicated in escape of Listeria monocytogenes from phagocytic vacuoles. Here we describe the pH-dependence of vacuolar perforation by LLO, using the membrane-impermeant fluorophore 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) to monitor the pH and integrity of vacuoles in mouse bone marrow-derived macrophages. Perforation was observed when acidic vacuoles containing wild-type L. monocytogenes displayed sudden increases in pH and release of HPTS into the cytosol. These changes were not seen with LLO-deficient mutants. Perforation occurred at acidic vacuolar pH (4.9-6.7) and was reduced in frequency or prevented completely when macrophages were treated with the lysosomotropic agents ammonium chloride or bafilomycin A1. We conclude that acidic pH facilitates LLO activity in vivo.

A phase II study of weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin as first-line chemotherapy in patients with locally advanced or metastatic gastric cancer.

BACKGROUND: Docetaxel plus cisplatin and 5-fluorouracil has become a new standard for treating advanced gastric cancer. However, high rates of severe neutropenia limit its application. Modification of the regimen could be the solution to get similar activity but less myelosuppression. METHODS: Patients with histologically confirmed, locally advanced, or recurrent/metastatic gastric adenocarcinoma without previous chemotherapy were enrolled. This regimen consisted of docetaxel (Tyxan, TTY, Taipei, Taiwan) 30-min infusion at a dose of 36 mg m(-2), followed by cisplatin 30 mg m(-2) infusion over 1 h on days 1 and 8, and oral tegafur/uracil 300 mg m(-2) per day plus leucovorin 90 mg per day on days 1-14, every 3 weeks. Tumour response was evaluated after every 2 cycles of treatment. RESULTS: From August 2007 to March 2009, 45 patients were enrolled. The median age was 56 years (range: 22-75). Among the 40 patients evaluable for tumour response, one achieved a complete response, 22 had partial responses and 11 had stable disease. The overall response rates of the evaluable and intent-to-treat (ITT) populations were 58% (95% CI: 41-74%) and 53% (95% CI: 38-68%), respectively. The disease control rates in these populations were 85% (95% CI: 70-94%) and 82% (95% CI: 68-92%), respectively. In the ITT analysis, the median time to progression and overall survival were 6.8 and 13.9 months, respectively. Major grade 3-4 toxicities were neutropenia (51%), anaemia (22%), diarrhoea (16%), and infections (20%). No patient died of treatment-related toxicities. CONCLUSION: Concurrent weekly docetaxel and cisplatin plus oral tegafur/uracil and leucovorin are effective and well tolerated in the treatment of advanced gastric cancer.

Providing essential clinical care for non-COVID-19 patients in a Seoul metropolitan acute care hospital amidst ongoing treatment of COVID-19 patients.

We assessed infection control efforts by comparing data collected over 20 weeks during a pandemic under a dual-track healthcare system. A decline in non-COVID-19 patients visiting the emergency department by 37.6% (P<0.01) was observed since admitting COVID-19 cases. However, patients with acute myocardial infarction (AMI), stroke, severe trauma and acute appendicitis presenting for emergency care did not decrease. Door-to-balloon time (34.3 (± 11.3) min vs 22.7 (± 8.3) min) for AMI improved significantly (P<0.01) while door-to-needle time (55.7 (± 23.9) min vs 54.0 (± 18.0) min) in stroke management remained steady (P=0.80). Simultaneously, time-sensitive care involving other clinical services, including patients requiring chemotherapy, radiation therapy and haemodialysis did not change.

The incidence and risk of second primary cancers in patients with nasopharyngeal carcinoma: a population-based study in Taiwan over a 25-year period (1979-2003).

BACKGROUND: Very few reports are available on the incidence and risk of second primary cancers in nasopharyngeal carcinoma (NPC) cases, and most of these are single-institution reviews with relatively small case numbers and short follow-up. PATIENTS AND METHODS: A population-based study was conducted. We quantified standardized incidence ratios (SIRs) and cumulative incidence of second cancers among 23 639 individuals with initial diagnoses of NPC. RESULTS: We found a 24% increased risk of second cancers in NPC patients compared with the general population [SIR = 1.24, 95% confidence interval 1.15-1.33]. Elevated SIRs were observed in the following second primary cancers: oral/pharyngeal, salivary gland, sarcoma, skin and leukemia/lymphoma. The cumulative incidence >10 years was 3.26%. The risk was higher in younger patients, especially those <40 years old. After diagnosis of second cancers, the median survival time was 1.7 years. CONCLUSIONS: This is the largest population-based study to date from a high-incidence area. We found that NPC is associated with an increased risk of second malignancies, which had a negative impact on the survival of patients who survived NPC.

Nod factor enhances calcium uptake by soybean.

Inoculation with rhizobia or application of Nod factors (lipo-chitooligosaccharides, LCOs) causes transient increases in cytosolic calcium concentration in root hairs of legume plants. We conducted experiments to evaluate whether application of LCO and inoculation with rhizobia improved (45)CaCl(2) uptake into soybean (Glycine max [L.] Merr.) leaves. Roots of soybean seedlings with one developing trifoliolate were immersed in Murashige and Skoog (MS) basal liquid medium containing treatment solutions and (45)CaCl(2), and the plants were incubated under continuous light. After 24 h, leaf samples were taken, and their radioactivity levels were determined. Addition of NodBj-V (C18:1 MeFuc) at a concentration of 10(-7) M increased (45)Ca(2+) uptake. Inoculation with genistein-induced Bradyrhizobium japonicum strain 532C and USDA3 also increased (45)Ca(2+) uptake; whereas, inoculation with strain Bj-168, a nodC-mutant incapable of producing LCO, did not. Rhizobia that do not normally nodulate soybean, i.e. Rhizobium leguminosarum, and Sinorhizobium meliloti did not affect calcium uptake, nor did the tetramer or pentamer of chitosan, or lumichrome. Surprisingly, Rhizobium sp. NGR234, which can nodulate some types of soybean, although without effective N(2)-fixation, also did not affect calcium uptake. This work suggests that the rhizobial symbiosis, in addition to its known role in provision of nitrogen fixation, also improves early calcium uptake into soybean plants.

Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice.

Using light and electron microscopy, we investigated the in vivo distribution of liposomes sterically stabilized by specific lipids which prolong their circulation in blood. Tissue distribution of sterically stabilized liposomes composed of distearoyl phosphatidylcholine:cholesterol:monosialoganglioside GM1 (10:5:1)-encapsulated 67Ga-Desferal indicates that more than 30% of liposomes still remain in the blood at 24 h after tail vein injection. Moreover, such liposomes accumulated in tumors (C-26 colon carcinoma cells implanted s.c.), reaching almost the same level of uptake as liver (approximately 20% injected dose/g tissue). The microscopic localization of liposomes labeled with encapsulated colloidal gold or rhodamine-labeled dextran coincided well with the tissue distribution. To evaluate circulation parameters, two sizes of gold-containing egg phosphatidylcholine:cholesterol:distearoyl phosphatidylethanolamine (derivatized at its amino position with a 1900 molecular weight segment of polyethylene glycol) (10:5:0.8) liposomes were injected. The plasma was examined by electron microscopy of negative-stained preparations at 0.5, 4, and 24 h after liposome injection. It was found that the ratio of small (less than 100 nm diameter) to large (greater than 100 nm) liposomes increased with time, indicating a much faster clearance of the larger liposomes. To detect the localization of liposomes in various tissues, appropriate samples were fixed 24 h after the injection of gold-containing liposomes (between 80 and 100 nm in diameter) composed of egg phosphatidylcholine:cholesterol:monosialoganglioside GM1 (10:5:1) or egg phosphatidylcholine:cholesterol:derivatized distearoyl phosphatidylethanolamine. The tissues examined for this study included normal liver, bone marrow, and implanted neoplasms. Silver-enhanced colloidal gold was found predominantly within Kupffer cells in the normal liver and within macrophages in the bone marrow. Rarely were any silver-enhanced gold particles detected in hepatocytes. In all preparations, electron microscopy revealed the presence of gold in endosomes and lysosomes of fixed sinusoidal lining macrophages in the liver and bone marrow. Peripheral to the implanted tumors, silver enhancement revealed gold in small blood vessels and focally beyond the vessel boundaries in extracellular spaces around tumor cells. Gold particles were not observed within the tumor cell cytoplasm. At the tumor border, nonenhanced gold was occasionally seen by electron microscopy in cells of the mononuclear phagocyte system. We obtained the same localization pattern as with silver enhancement by using an alternative aqueous content marker, rhodamine B isothiocyanate-dextran. We conclude that liposomes of specific composition, which have the ability to remain in circulation with a half-life of 12-24 h, are also able to transverse the endothelium of small blood vessels, including those in tumors, and extravasate into extracellular spaces.(ABSTRACT TRUNCATED AT 400 WORDS)