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Biomedical subjects

S H Yeh

Publications and source records attributed to S H Yeh.

At least 19 recordsLinked to original sources

The measurement of 60Co contaminated rebar buildings with thermoluminescence dosemeters.

Three contaminated housing units, yielding annual dose levels of 6, 22 and 57 mSv, were selected randomly from identified radiation contaminated buildings (RCBs) to perform this experiment. The results are presented of a study to investigate the probability of finding RCBs by using eight thermoluminescence dosemeters (TLDs) for each suspected radiation contaminated housing unit. The results revealed that, for these three housing units, the probabilities of detecting contaminated housing units using eight TLDs were 93%, 86% and 99%, respectively. The number of TLDs required for such a determination depended strongly on both the radiation contaminated level (i.e., the activity) in the housing unit and the distribution of contaminated columns and beams in the house.

Air Pollution, Indoor↗

A role for the PI-3 kinase signaling pathway in fear conditioning and synaptic plasticity in the amygdala.

Western blot analysis of neuronal tissues taken from fear-conditioned rats showed a selective activation of phosphatidylinositol 3-kinase (PI-3 kinase) in the amygdala. PI-3 kinase was also activated in response to long-term potentiation (LTP)-inducing tetanic stimulation. PI-3 kinase inhibitors blocked tetanus-induced LTP as well as PI-3 kinase activation. In parallel, these inhibitors interfered with long-term fear memory while leaving short-term memory intact. Tetanus and forskolin-induced activation of mitogen-activated protein kinase (MAPK) was blocked by PI-3 kinase inhibitors, which also inhibited cAMP response element binding protein (CREB) phosphorylation. These results provide novel evidence of a requirement of PI-3 kinase activation in the amygdala for synaptic plasticity and memory consolidation, and this activation may occur at a point upstream of MAPK activation.

Afferent Pathways↗

Antibody responses to bovine parainfluenza virus type 3 (PIV3) vaccination and human PIV3 infection in young infants.

A phase 2 clinical trial was conducted to evaluate the antibody responses to bovine parainfluenza virus type 3 (bPIV3) vaccination in young infants. Three groups were tested as follows: placebo (n=66) and 10(5) (n=64) or 10(6) (n=62) TCID(50) of bPIV3. The vaccine or placebo was administered intranasally at ages 2, 4, 6, and 12-15 months, and serum specimens were collected at ages 2, 6, 7, 12-15, and 13-16 months. Serum hemagglutination inhibition (HI) and IgA antibody titers against bPIV3 and human PIV3 (hPIV3) were measured. The results indicate that antibody responses to bPIV3 vaccination are more likely to be detected by the bPIV3 IgA and HI assays than by the hPIV3 IgA and HI assays, that bPIV3-induced antibody response can be differentiated from hPIV3-induced antibody response most reliably by comparing bPIV3 and hPIV3 HI titers, and that bPIV3 vaccine prevents vaccine recipients from developing antibody profiles of hPIV3 primary infection.

Administration, Intranasal↗

Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma.

BACKGROUND & AIMS: Cirrhotic nodules have long been assumed to be the precancerous lesions of hepatocellular carcinoma (HCC). We thus investigated the allelic imbalance (AI) in cirrhotic nodules to define the genetic aberrations in early hepatocarcinogenesis. METHODS: One hundred eighty cirrhotic nodules from 7 female patients with HCC were collected by microdissection. Their clonality nature was assessed by examining the X chromosome methylation pattern. AI in monoclonal cirrhotic nodules and the corresponding HCCs were analyzed with microsatellite polymorphic markers. RESULTS: One hundred one out of 180 nodules (56.1%) were monoclonal and the average fractional AI (FAI) was 21%, lower than the 40% in HCC. Their overall AI patterns differed significantly from that in HCC (P < 0.001) with FAI on 2q, 4q, 8p, and Xq higher than the mean value. Comparison of FAI in nodules (stratified by increasing total AI events) further revealed a progressive increase of FAI on 4q, 8p, and Xq. In contrast, FAI on 1p, 13q, 16q, and 17p were low in nodules but rose above the mean only in HCC. CONCLUSIONS: About half of the cirrhotic nodules are monoclonal and already have chromosome aberrations. AI on 4q, 8p, and Xq may be the earlier mutations, whereas AI on 1p, 13q, 16q, and 17p occurs late in hepatocarcinogenesis.

Adult↗

Safety and immunogenicity of a pentavalent diphtheria, tetanus, pertussis, hepatitis B and polio combination vaccine in infants.

INTRODUCTION: The objectives of this study were to evaluate the safety and immunogenicity of a new combination vaccine (DTaP-HB-IPV) containing diphtheria, tetanus, acellular pertussis and hepatitis B (HB) and a new inactivated poliovirus vaccine (IPV) manufactured by GlaxoSmithKline (GSK). This vaccine was given in an all IPV or sequential IPV and oral polio vaccine (OPV) schedule. Another combination vaccine, DTaP-HB (GSK), was similarly evaluated given with OPV or IPV. METHODS: Four hundred infants were randomized into one of four study groups and immunized at 2, 4 and 6 months of age. Group A received three doses of DTaP-HB-IPV; Group B received DTaP-HB-IPV at 2 and 4 months and DTaP-HB with OPV (Orimune) at 6 months; Group C received three doses of DTaP-HB with licensed IPV (IPOL) administered separately; Group D received separate doses of OPV, DTaP (Infanrix; GSK) and HB (Engerix; GSK). All subjects received conjugate Haemophilus influenzae type b vaccine (Hib) (OmniHIB) at 2, 4 and 6 months of age given at a separate injection site. Subjects who returned at 12 to 18 months of age (229) received booster immunization with DTaP and Hib. Safety was evaluated after each vaccine dose. Blood was drawn before the first dose and one month after the third dose as well as before and after the booster dose. RESULTS: There were no vaccine-related serious adverse events in any group after any vaccine dose. Minor systemic and local adverse events were also not significantly different among the four groups after any dose. There were no differences in the immune response rates for Hib, HB, polio (types 1, 2 and 3), diphtheria, tetanus or pertussis antigens (pertussis toxin, filamentous hemagglutinin, pertactin) among groups, although there were some quantitative differences in specific antibody titers among groups. DTaP-HB-IPV and DTaP-HB combination vaccines had safety and immunogenicity equivalent to those of standard individually administered vaccines. The new IPV was not inferior to IPOL. CONCLUSION: Use of the pentavalent combination vaccine would greatly reduce the number of required injections during the first 2 years of life, thereby simplifying the immunization schedule, enhancing compliance and facilitating acceptance of additional injections engendered by introduction of newer vaccines.

Diphtheria-Tetanus-acellular Pertussis Vaccines↗

Strategies for development of combination vaccines.

BACKGROUND: The increasing complexity of the recommended childhood immunization schedule has resulted in the need for combination vaccines. METHODS: Through an extensive review of the current literature, various strategies and issues related to the development of combination vaccines are discussed. RESULTS: Issues that should be considered when combining vaccine components include the current childhood immunization schedule, compatibility of components, availability of antigens for targeted diseases, safety, efficacy, immunogenicity and route of delivery. When choosing an appropriate combination of antigen(s)/serotype(s) for a global or national formulation, careful consideration must be made when selecting serotypes to combine depending on the market or area of use. It is important to know that potential interactions can involve other components of the vaccines, including buffers, adjuvants and preservatives. The Food and Drug Administration requires that the combination not only have immunogenicity comparable with those of the component vaccines, but that its safety profile be comparable with the most reactogenic component. The Food and Drug Administration also recommends that a test of noninferiority be performed, such that the combination performs similarly to the separate components with regard to antibody titers. CONCLUSIONS: Combination vaccines are critical to the success of vaccination programs, and each new combination must be carefully studied to ensure comparable safety and immunogenicity of the individual components.

Antigens↗

[The outcomes of restraint reduction program in nursing homes].

One of the problems in nursing home care in Taiwan is resident restraint, including physical and chemical restraints. This pre-experimental study was conducted to investigate whether a restraint reduction program could reduce the prevalence of restraint in nursing homes. Three registered nursing homes were randomly selected from nursing homes in the Kaohsiung area. Staff and residents of these nursing homes were educated in restraint alternatives, balance training and managing behavior problems in one month of interventions. Three days before and after interventions, prevalence of restraints, falls, and of pressure sores, balance reaction, frequency of agitation, use of psychotic drugs, as well as the restraint knowledge of the nursing staff, was measured. After the restraint reduction program, the prevalence of restraint and frequency of resident agitation decreased significantly. The prevalence of falls and pressure sores of residents was not changed significantly. The restraint knowledge of the nursing staff significantly increased after the restraint reduction program. The information from this study led to a better strategy to reduce restraint for the elderly in nursing homes. The results could also provide a model to improve the quality of care in nursing homes in Taiwan.

Aged↗

Minimal toxicity to myeloid progenitor cells of weekly 24-hr infusion of high-dose 5-fluorouracil: direct evidence from colony forming unit-granulocyte and monocyte (CFU-GM) clonogenic assay.

Although very high doses of 5-fluorouracil was used in the weekly 24-h infusion, high-dose 5-fluorouracil (2600 mg/m2/week) and leucovorin (500 mg/m2/week) protocol, myelosuppression was surprisingly low. The current study was conducted to investigate the possible mechanism underlying the low myelosuppression. To mimic the clinical situation, peripheral blood progenitor cells collected from 12 patients were used for colony forming unit-granulocyte and monocyte clonogenic assay; and 2 representative modes of 5-fluorouracil exposure (30 min. versus 24 hr) were examined for cytotoxic effects on human myeloid progenitor cells. Previous pharmacokinetic studies have estimated the concentrations of 5-fluorouracil in the bone marrow to be 200-400 microM and 1-2 microM for the 30 min. infusion (600-900 mg/m2) and the 24 hr-infusion (1000-2000 mg/m2) regimens, respectively. The results of our colony-forming unit-granulocyte and monocyte clonogenic assay showed that 24-hr exposure to 5-fluorouracil (2 microM) and 30 min. exposure to 5-fluorouracil (100 microM) resulted in 27.2% and 78.2% inhibition of the colony formation, respectively. Our data provided direct evidence which may explain why myelotoxicity is significantly less in weekly 24 hr infusion of fluorouracil than in the conventional bolus regimens.

Adolescent↗

Chromosomal changes and clonality relationship between primary and recurrent hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is highly malignant and prone to recur after surgical treatment. Differentiation between a true relapse of HCC and a second primary tumor is of clinical importance. However, no convenient method is currently available. METHODS: Comparative genomic hybridization (CGH) was used to analyze 31 pairs of initial and recurrent HCC samples obtained from patients undergoing 2 consecutive surgeries. The resulting chromosomal aberration profiles were used as genomic fingerprints to determine tumor clonalities and their relationships. RESULTS: Eleven recurrent tumors with high clonal relationship (CR) values (>0.95) were found to be relapsed HCCs, and 11 tumors with CR values close to 0 were found to be second primary HCCs. The other 9 paired samples had inconclusive CR values between 0.95 and 0.4. Two were confirmed by hepatitis B virus integration and X chromosome inactivation analysis to be de novo cancers (CR values, 0.35 and 0. 23, respectively). Initial HCCs that subsequently relapsed accumulated more chromosomal aberration events than those that developed de novo HCC (mean, 16.1 +/- 4.5 vs. 5.4 +/- 4.8 events; P < 0.01). Also, they more frequently showed gains on chromosome arms 3q, 6p, 8q, and 17q and losses on 4q and 16p. CONCLUSIONS: CGH is useful for chromosomal aberration study and tumor clonality analysis. More and characteristic genomic changes in the initial HCC suggest that subsequent tumor recurrence is a true relapse.

Adult↗

Prolonged and enhanced suppression of thymidylate synthase by weekly 24-h infusion of high-dose 5-fluorouracil.

We have recently demonstrated that HDFL (high-dose 5-FU 2600 mg m-2 week-1 and leucovorin 500 mg m-2 week-1, weekly 24-h infusion) is highly active in the treatment of gastric cancer. To further clarify the possible mechanism underlying the improved activity of HDFL compared with conventional 5-FU regimens, we conducted in vitro studies examining the effect of these regimens on the differential regulation of thymidylate synthase (TS) in NCI-N87, a human gastric cancer cell line. The expected serum concentrations of 5-FU are 100-200 mM (lasting for less than 30 min) and 5-10 mM (lasting for 24 h) for the conventional 5-FU regimens (bolus injection or short intravenous infusion of 5-FU 370-500 mg m-2) and the HDFL regimens, respectively. Western blot analysis revealed that 24-h exposure of NCI-N87 to 2.5-10.0 mM of 5-FU resulted in a dose-dependent depletion of free TS, lasting for more than 24 h. In contrast, 30-min exposure of NCI-N87 to 200 mM of 5-FU resulted in a less than 12-h depletion of free TS. Moreover, 24-h exposure to 5-FU resulted in a higher S-phase blockade and enhanced cytotoxicity. In both modes of 5-FU treatment, the initial rapid depletion of free TS was accompanied by a rapid increment of a higher-molecular-weight TS molecule, suggesting that rapid formation of the ternary complex was the key mechanism of 5-FU action during this period. Northern blot analysis showed that the steady-state mRNA of TS was not affected by either of the schedules. We conclude that 24-h exposure of gastric cancer cells to low concentration of 5-FU resulted in better suppression of free TS, a higher degree of S-phase blockade, and enhanced cytotoxicity compared to 30-min exposure to high concentration of 5-FU. These in vitro results may help explain the improved clinical efficacy of HDFL regimens compared to conventional 5-FU regimens.

Antimetabolites, Antineoplastic↗

Parapharyngeal abscess due to cat-scratch disease.

The spectrum of illness attributed to cat-scratch disease (CSD) continues to expand. Although a common cause of cervical adenitis in children, CSD has not been associated as a cause of deep fascial space infections of the head and neck. We describe a child with extensive parapharyngeal adenitis and abscesses due to CSD confirmed by histological and serological evaluations.

Abscess↗

11C-acetate clearance in nasopharyngeal carcinoma.

This study assessed 11C-acetate turnover (clearance) in nasopharyngeal carcinoma (NPC). Data were acquired by dynamic PET after the intravenous injection of 4.625 MBq.kg-1 body weight of 11C-acetate for 30 min. Tomograms were reconstructed and evaluated visually. A time-activity curve of the nasopharynx and neck was generated and the clearance rate of 11C-acetate from the nasopharynx in the slow phase and from NPC was calculated using 0.693/T1/2. Ten patients with nasopharyngeal carcinoma and nine normal subjects were studied. The clearance of 11C-acetate from the normal nasopharynx was rapid and biexponential, in contrast to the rapid uptake followed by extremely slow clearance in patients with NPC. The clearance rate (mean +/- S.D.) was 0.0074 +/- 0.0042 in NPC and 0.0263 +/- 0.0152 in controls in the slow phase, being significantly different between the two groups with no overlap. All nasopharyngeal carcinomas were clearly visualized, in contrast to no obvious retention in the normal nasopharynx. Our initial results indicate that 11C-acetate clearance can be used to differentiate nasopharyngeal carcinoma from a normal nasopharynx. This finding may lead to new applications of 11C-acetate in oncology.

Acetates↗

Whole-body PET with (fluorine-18)-2-deoxyglucose for detecting recurrent ovarian carcinoma. Initial report.

OBJECTIVE: To investigate positron emission tomography (PET) with (fluorine-18)-2-deoxyglucose (FDG) for detecting recurrent ovarian carcinoma. STUDY DESIGN: Wholebody FDG-PET scanning was performed on five patients before surgical exploration. All five patients were suspected of having recurrence based upon clinical findings and underwent surgery after scanning. RESULTS: In all five patients, PET images demonstrated increased FDG uptake in a distribution that correlated with surgical-pathologic findings (100%); computer tomography can detect 60% of such patients with malignant disease. Two cases with unexplained elevated serum CA-125 had lesions localized by PET. CONCLUSION: Recurrence of ovarian carcinoma was clearly imaged with FDG-PET and was confirmed by surgical pathology. FDG-PET might be a fairly effective tool for detecting recurrent ovarian carcinoma.

CA-125 Antigen↗

Gene therapy with tumor vaccine increases the survival of hepatoma-bearing mice.

BACKGROUND: Tumor vaccines combined with cytokine gene therapy and Bacillus Calmette-Guérin (BCG) were tested for prevention and therapeutic effects in the H6 mouse hepatoma model. METHODS: Plasmid DNA of expression vectors carrying cDNA of mouse interleukin (IL)-2 and mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) were used for transfection to obtain H6 mouse hepatoma cells that secreted IL-2 (H6/IL-2) or GM-CSF (H6/GM-CSF). For tumor prevention, groups of mice were immunized twice with irradiated tumor cells with untransduced H6, H6/IL-2, H6/GM-CSF, or an equal mixture of H6/IL-2 and H6/GM-CSF. Three weeks later, these mice were inoculated subcutaneously with live H6 hepatoma cells, and tumor growth was measured. For therapeutic studies, mice first inoculated with live H6 cells were treated three days later with various irradiated tumor cell vaccines alone or in combination with BCG. Subsequent tumor growth was measured. RESULTS: In tumor prevention studies, significant protection from tumor growth has been observed in animals vaccinated with irradiated cytokine-secreting H6 cells compared with those immunized with irradiated parental H6 cells. In tumor therapy studies, subsequent administration of irradiated H6/GM-CSF cells in combination with BCG impeded the tumorigenicity of preinoculated live H6 hepatoma cells. CONCLUSIONS: These results suggest that cytokine-secreting tumor vaccines have a prophylactic effect and BCG, in combination with irradiated H6/GM-CSF cells, shows a synergistic effect on delaying the growth of H6 mouse hepatomas.

Animals↗

Fluorine-18 fluoromisonidazole tumour to muscle retention ratio for the detection of hypoxia in nasopharyngeal carcinoma.

In vivo demonstration of hypoxia is of significance for tumour patient management. Fluorine-18 fluoromisonidazole ([18F]FMISO) is a proven hypoxic imaging agent. We developed an [18F]FMISO tumour to muscle retention ratio (TMRR) for the detection of tumour hypoxia in nasopharyngeal carcinoma (NPC). Data were acquired by positron emission tomography (PET) of the nasopharynx and neck after intravenous injection of 370 MBq of [18F]FMISO. Two imaging protocols were adopted: a long protocol for comprehensive dynamic information and a short protocol for a simple, clinically convenient imaging procedure. Tomograms were reconstructed and evaluated visually. ROI analysis on the basis of time-activity curve evaluation was performed to calculate the TMRR of NPC or cervical nodal metastases (CNMs) in relation to the suboccipital muscles at 2 h. The calculation of the TMRR was exactly the same for both the long and the short protocol as two 30-min composite frames had been created immediately after intravenous injection and 2 h after injection of [18F]FMISO in the long protocol. The normal tissue to muscle retention ratio (NTMRR) was derived similarly from the normal nasopharynx. The data of 12 controls and 24 patients with NPC were analysed. The long protocol was used in 15 patients, and the short protocol in nine. In controls, the mean NTMRR+/-1 SD was 0.96+/-0.14. The mean TMRRs for NPC and CNMs were 2.56+/-1.50 and 1.35+/-0.51, respectively; these values were significantly higher than the mean NTMRR for normal controls (P<0.005 in each case). At the retention threshold value of 1.24, tumour hypoxia occurred in 100% of the primary lesions of NPC and 58% of CNMs. The TMRR for undifferentiated carcinoma was significantly lower than that for non-keratinized carcinoma (P<0.05). The [18F]FMISO TMRR is a simple and clinically useful index for detecting tumour hypoxia in NPC.

Carcinoma↗

Detection of anaerobic odontogenic infections by fluorine-18 fluoromisonidazole.

Odontogenic infections are a potential risk for patients who receive cervicofacial radiotherapy and should be treated before irradiation. Anaerobic microbial infections are the most common causes. This study assessed the value of the hypoxic imaging agent fluorine-18 fluoromisonidazole (FMISO) in detecting anaerobic odontogenic infections. Positron emission tomography (PET) imaging was performed at 2 h after injection of 370 MBq (10 mCi) of FMISO in 26 nasopharyngeal carcinoma patients and six controls with healthy teeth. Tomograms were interpreted visually to identify hypoxic foci in the jaw. All patients received thorough dental examinations as a pre-radiotherapy work-up. Fifty-one sites of periodontitis, 15 periodontal abscesses, 14 sites of dental caries with root canal infection, 23 sites of dental caries without root canal infection, and seven necrotic pulps were found by dental examination. Anaerobic pathogens were isolated from 12 patients. Increased uptake of FMISO was found at 45 out of 51 sites of periodontitis, all 15 sites of periodontal abscess, all 14 sites of dental caries with root canal infection, all seven sites of necrotic pulp and 15 sites of dental caries without obvious evidence of active root canal infection. No abnormal uptake was seen in the healthy teeth of patients or in the six controls. The diagnostic sensitivity, specificity, positive and negative predictive values, and accuracy of FMISO PET scan in detecting odontogenic infections were 93%, 97%, 84%, 99% and 96%, respectively. 18F-fluoride ion bone scan done in three patients showed that 18F-fluoride ion plays no role in the demonstration of anaerobic odontogenic infection. FMISO PET scan is a sensitive method for the detection of anaerobic odontogenic infections, and may play a complementary role in the evaluation of the dental condition of patients with head and neck tumours prior to radiation therapy.

Bacteria, Anaerobic↗

Allelic loss on chromosomes 4q and 16q in hepatocellular carcinoma: association with elevated alpha-fetoprotein production.

BACKGROUND & AIMS: In human hepatocellular carcinoma, restriction fragment length polymorphism analysis has shown frequent allelic loss on chromosomes 4q and 16q. To better define the commonly affected region for further positional cloning of the putative tumor-suppressor genes contained in these two chromosome arms, microsatellite polymorphism analysis was conducted to analyze extensively the allelic loss on both chromosome loci. METHODS: DNA from 42 pairs of large hepatocellular carcinoma (> 5 cm) and corresponding nonneoplastic liver tissues were prepared. Allelic loss on chromosome 4q and 16q was investigated by 13 or 12 sets of microsatellite polymorphic markers. RESULTS: The frequency of allelic loss on chromosome 16q was 70%, and the common region was mapped to 16q22-23. An even higher frequency (77%) was found on chromosome 4q with the common region mapped to 4q12-23. The allelic loss of chromosome 4q was significantly associated with hepatocellular carcinoma of elevated serum alpha-fetoprotein but not with those of normal level (91% vs. 30%; Fisher's Exact Test, two-tailed P = 1.12 x 10(-4)). CONCLUSIONS: The results form the basis for further positional cloning of putative tumor-suppressor genes on chromosome 4q and 16q. Moreover, the one on chromosome 4q might shed light on the mechanism of alpha-fetoprotein expression in hepatocellular carcinoma.

Alleles↗