Assessment of epidermal growth factor receptor with 99mTc-ethylenedicysteine-C225 monoclonal antibody

Epidermal growth factor receptor (EGFR) plays an important role in cell division and cancer progression, as well as angiogenesis and metastasis. Since many tumor cells exhibit the EGFR on their surface, functional imaging of EGFR provides not only a non-invasive, reproducible, quantifiable alternative to biopsies, but it also greatly complements pharmacokinetic studies by correlating clinical responses with biological effects. Moreover, molecular endpoints of anti-EGFR therapy could be assessed effectively. C225 is a chimeric monoclonal antibody that targets the human extracellular EGFR and inhibits the growth of EGFR-expressing tumor cells. Also, it has been demonstrated that C225, in combination with chemotherapeutic drugs or radiotherapy, is effective in eradicating well-established tumors in nude mice. We have developed 99mTc-labeled C225 using ethylenedicysteine (EC) as a chelator. This study aimed at measuring uptake of 99mTc-EC-C225 in EGFR+ tumor-bearing animal models and preliminary feasibility of imaging patients with head and neck carcinomas. In vitro Western blot analysis and cytotoxicity assays were used to examine the integrity of EC-C225. Tissue distribution studies of 99mTc-EC-C225 were evaluated in tumor-bearing rodents at 0.5-4 h. In vivo biodistribution of 99mTc-EC-C225 in tumor-bearing rodents showed increased tumor-to-tissue ratios as a function of time. In vitro and biodistribution studies demonstrated the possibility of using 99mTc-EC-C225 to assess EGFR expression. SPECT images confirmed that the tumors could be visualized with 99mTc-EC-C225 from 0.5 to 4 h in tumor bearing rodents. We conclude that 99mTc-EC-C225 may be useful to assess tumor EGFR expression. This may be useful in the future for selecting patients for treatment with C225.     

Evaluation of cell proliferation in ear and lymph node using BrdU immunohistochemistry for mouse ear swelling test

The mouse ear swelling test (MEST) was developed as an alternative to guinea pig models for measuring the contact sensitization potential. However, the MEST relies on the quantitative measurement of ear swelling by micrometer as the means of determining the endpoint. The purpose of this study was to investigate the possibility of using cell proliferation in the ear and lymph node by bromodeoxyuridine (BrdU) immunohistochemistry as a reliable marker for MEST. Female Balb/c mice were treated by the topical application of various sensitizers, 2,4-dinitrochlorobenzene (DNCB), toluene diisocyanate (TDI) and α-hexylcinnamaldehyde (HCA) and an irritant, sodium lauryl sulfate (SLS) following the protocol of MEST. The proliferation of cells in the ear and auricular lymph node was analyzed by BrdU incorporations into cells. There were significant increases in the cell proliferations of the ear and auricular lymph node in mice treated with DNCB and TDI compared to the vehicle control. All allergens and the irritant were correctly identified by the MEST using BrdU immunohistochemistry of lymph node responses. The standard MEST assay showed positive results in the case of the strong sensitizers, DNCB and TDI. However, HCA and SLS were not correctly identified in the ear swelling assay. These results suggest that the measurement of cell proliferation in the auricular lymph node using BrdU immunohistochemistry could provide a reliable marker for MEST.     

Transcaruncular approach to blowout fractures of the medial orbital wall

Transcutaneous and transconjunctival approaches are still frequently used to repair orbital wall fractures. However, medial orbital wall fracture remains a challenging area for plastic surgeons due to technical difficulties and postoperative scars. The transcaruncular approach is described and we present our experience with this approach to access the medial orbital wall in 10 patients with blowout fracture in the medial orbital region. All patients were corrected satisfactorily without cutaneous scar. The transcaruncular approach is a useful technique to repair medial orbital wall fractures.     

Serum cytokine profiles in patients with Plasmodium vivax malaria: a comparison between those who presented with and without hepatic dysfunction

The aim of this study was to compare the serum cytokine profiles of Plasmodium vivax malaria patients who presented with and without hepatic dysfunction. This is a retrospective analysis of 74 consecutive cases of P. vivax malaria seen at 3 military hospitals near the Demilitarized Zone in South Korea from 1999 to 2000. All patients studied were adult active duty servicemen. On admission, the mean (+/- SEM) age of the patients who presented with (n = 36) and without hepatic dysfunction (n = 38) was 21.6 +/- 0.24 and 22.5 +/- 0.44 years, respectively (P = 0.72). On admission, there was no significant difference between the 2 patient populations in terms of mean temperature, haemoglobin level, haematocrit, total white blood cell count, platelet count, parasite index, and serum concentration of transforming growth factor-beta. Plasmodium vivax malaria patients who presented with hepatic dysfunction had significantly higher mean serum concentrations of soluble Fas ligand, interleukin (IL)-l, IL-4, IL-6, IL-10, tumor necrosis factor-alpha, and interferon-gamma than those without hepatic dysfunction, suggesting the involvement of these cytokines in the development of hepatic dysfunction. The mean serum concentration of IL-12 was significantly lower in patients with hepatic dysfunction. The mean body temperature was not significantly different between the 2 patient populations.     

Antibacterial compounds from the leaves of<Emphasis Type="Italic">Acanthopanax senticosus</Emphasis>

Chiisanogenin (1), hyperin (2) and chiisanoside (3) were isolated from the leaves of Acanthopanax senticosus, and were tested for their inhibitory activities against 6 strains of bacteria. Among them, chiisanogenin (1) revealed broad but moderate antibacterial activities against G (+) and G (-) bacteria, the minimum inhibitory concentration (MIC) being in the range of 50-100 microg/ml.     

Hypocholesterolemic property of<Emphasis Type="Italic">Yucca schidigera</Emphasis> and<Emphasis Type="Italic">Quillaja saponaria</Emphasis> extracts in human body

This study was undertaken to observe the effects of the blend of partially purified Yucca schidigera and Quillaja saponaria extracts on cholesterol levels in the human's blood and gastrointestinal functions, and to determine if a new cholesterol-lowering drug can be developed by the further purification of the extracts. Ultrafiltration and sequential diafiltration increased the amounts of steroidal saponin in aqueous yucca extract and terpenoid saponin in aqueous quillaja extract from 9.3% and 21.4% to 17.2% and 61.8%, respectively. Taking 0.9 mg of the blend (6:4, v:v) of the resulting filtrates a day for 4 weeks resulted in the decreases in total and LDL cholesterol levels in blood plasma of hyper-cholesterolemic patients with enhancement in gastrointestinal symptoms of patients.     

Synthesis and PGE<Subscript>2</Subscript> inhibitory activity of vinylated and allylated chrysin analogues

Vinylated and allylated chrysin analogues were prepared as congeners of prenylated flavonoids and evaluated their anti-inflammatory activity. 8-Substituted chrysin analogues were prepared from 2'-hydroxy-3'-iodo-4',6'-dimethoxyacetophenone in 3 steps. 3-Allylated chrysin analogues were prepared from chrysin in 3 steps. Synthesized chrysin analogues (4, 5 and 8) showed moderate inhibitory activities of PGE2 production from LPS-induced RAW 264.7 cells.     

High radiochemical yield synthesis of 3'-deoxy-3'-[18F]fluorothymidine using (5'-O-dimethoxytrityl-2'-deoxy-3'-O-nosyl-beta-D-threo pentofuranosyl)thymine and its 3-N-BOC-protected analogue as a labeling precursor

We prepared 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) from 3'-O-nosyl thymidine derivative 3 or its pyrimidine ring N-BOC-protected analogue 5 and optimized [(18)F]fluorination condition for a high radiochemical yield. The optimal condition for [(18)F]fluorination with precursor 3 was 30 mg (41.1 micromol)/300 microl CH(3)CN at 130 degrees C for 5 min, while precursor 5 required 34 mg (40 micromol)/300 microl CH(3)CN at 110 degrees C for 5 min. After HPLC purification at neutral pH, we achieved high radiochemical yields of 40 +/- 5.2% and 42 +/- 5.4% (decay-corrected) within 60 min of preparation time with radiochemical purities of >97%.     

Clinical usefulness of human cytomegalovirus antigenemia assay after kidney transplantation

BACKGROUND: Human (H) cytomegalovirus (CMV) infections are a major cause of morbidity and mortality among kidney transplants. We performed a prospective study to evaluate the clinical usefulness of HCMV antigenemia assay for preemptive treatment after kidney transplantation. METHODS: A total of 100 patients were followed up by HCMV antigenemia assay at posttransplantation weeks 1, 3, 5, 7, 9, 13, 17, and 21. Asymptomatic patients with positive antigenemia were observed without specific antiviral therapy. RESULTS: Most patients had been given cyclosporine A- and prednisolone-based immunosuppressive therapy (99.0%) and were HCMV seropositive before transplantation (99.0%). A positive antigenemia assay was detected in 41 patients among 97 eligible patients. Symptomatic CMV diseases were observed in 10 of 41 patients. HCMV infections were related to history of acute rejection and use of antithymocyte globulin. HCMV-related symptoms and signs were clearly correlated with the level of antigenemia. All patients who had an HCMV antigenemia titer of higher than 50 per 400,000 leukocytes developed HCMV-related symptoms and signs during the follow-up period. This criterion showed the highest positive predictive value and specificity in the development of symptomatic HCMV infection. CONCLUSIONS: Data suggest that HCMV antigenemia titer can be used as a useful guide to preemptive treatment of HCMV infection after kidney transplantation in HCMV-positive donor and recipient.