Biomedical subjects
Publications and source records attributed to C C Li.
A case of acute progressive disseminated histoplasmosis complicated with hypercalcemia is reported and the literature is reviewed. This and the previously reported cases imply that physicians should have a higher index of suspicion for this infection and the probable underlying diseases resulting from impaired cellular-mediated immunity when encountering patients with hypercalcaemia.
To evaluate the outcomes of unrelated bone marrow transplantation facilitated by TCTMDR, we focused on 48 marrow transplants performed in Taiwan during the period May 1994 to June 1997. Follow-up of these 48 cases was made up to 30 May 1998. The average length of follow-up was 328 days (range 7-1385 days). All the donor/recipient pairs were HLA-A, B and DR matched and were divided into two risk groups based on diagnosis and stage of disease. There were 24 standard risk and 24 high risk patients. Engraftment occurred in 40 patients (83.3%). Acute and chronic GVHD was observed in 80% of evaluable patients and accounts for 41% of deaths. The second leading cause of death was infection, accounting for 35% of deaths. The overall probability of survival for the 48 patients after BMT over 2 years was 33.3% (95% CI 19.67-46.32%). The probability of survival for standard risk and high risk groups was 54% and 8%, respectively. In multivariate analysis, patients who were younger, in the standard risk group, or with a shorter search interval showed a higher survival probability.
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The computed radiography (CR) technique, also known as the storage phosphor imaging technique, has evolved to be a major candidate for large-scale implementation of digital radiography during the past decade. In order to obtain a reasonable spatial resolution, the storage phosphor plate used is generally limited in thickness. This leads to X rays being only partially absorbed by the detector. Useful information may be contained in the X rays transmitted through the detector. Multiple-plate imaging techniques may be used to capture and utilize the X rays more efficiently. In this paper, an image fusion method, based on the Rayleigh principle and the Karhunen-Loeve (K-L) transform, is presented for optimizing the signal-to-noise ratio (SNR) of the fused image on a pixel-by-pixel basis. Because the multiple-plate images contain the same structural information, the signal components of the images are highly correlated with one another. Thus, the K-L transform is applied to decompose each of the multiple-plate images into an eigen image (the estimated signal) and a residual image (the estimated noise). An average representation entropy measure is maximized for selecting the number of eigen components to be included in the signal estimation. An experimental study, using an anthropomorphic chest phantom, is presented to illustrate pixelwise fusion of multiple-plate images. Experimental results show that the SNR of the fused image was improved by 12-48%, depending upon the anatomical regions of interest in the image.
The c-rel proto-oncogene product, c-Rel, belongs to the Rel/NF-kappaB transcription factor family, which regulates a large variety of cellular functions. The activation of NF-kappaB involves the degradation of the inhibitor, IkappaB, through the ubiquitin-proteasome (Ub-Pr)-mediated pathway. Here we report that the turnover of c-Rel is also regulated by the Ub-Pr pathway, thus adding another level of complexity to the regulation of NF-kappaB. High molecular weight ubiquitinated c-Rel conjugates are detected in cells and accumulate in cells treated with proteasome inhibitors. In a cell-free in vitro degradation assay, c-Rel is degraded specifically through the Ub-Pr pathway. N-terminally truncated c-Rel is readily degraded, implying the dispensability of N-terminal sequence; in contrast, a series of deletion mutants missing C-terminal sequences display a reduced susceptibility to the degradation. Interestingly, the sequence between residues 118 and 171 of c-Rel, i.e. the region immediately following the c-Rel/v-Rel homology domain, appears to play an important role in mediating ubiquitin conjugation and the subsequent degradation. Together with our previous study showing an elevated tumorigenic potential for C-terminally truncated mutants, our data suggest that the C-terminal domain of c-Rel plays an important role in mediating c-Rel degradation and growth control.
Polo-like kinase (Plk) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Plk protein levels are low or undetectable in terminally differentiated cells and tissues and its expression is strongly correlated with cell growth. Plk protein and enzymatic activity are regulated by multiple mechanisms during cell cycle progression. During G1 Plk levels are low but increasing amounts of protein are detected during S phase and the highest amounts during G2M. Transcription of Plk message is specifically repressed during G1 but that cannot entirely account for the rapid disappearance of Plk protein at the end of mitosis. In this report we show that Plk protein can be degraded in vitro by partially purified proteasomes and that specific proteasome inhibitors can block Plk protein degradation both in vitro and in vivo. We also detected high molecular weight polyubiquitinated forms of Plk by immunoprecipitation and immunoblotting and confirmed that Plk, like other mitotic regulators, is targeted for destruction at the end of mitosis through the ubiquitin-proteasome mediated degradation pathway.
NF-kappa B/Rel family plays a pivotal role in a wide variety of cellular functions including growth, development, apoptosis and stress responses. Recent studies indicated that NF-kappa B is also involved in the cell cycle regulation, and high expression of c-Rel results in a cell cycle arrest at the G1/S-phase transition (Bash, J., Zong, W,-X., and Gelinas, C. (1997) Mol. Cell. Biol. 17, 6526-6536). Here we report the detection of Cdk2, a critical kinase responsible for the G1/S-phase transition, in immune complexes precipitated by the NF-kappa B antisera. Cdk2 and NF-kappa B association was detected by co-precipitation in the nuclear lysates of the G1/S-phase cells, and was found in cultured cell lines and in T cells purified from human peripheral blood. Using an affinity column containing the C-terminal peptide of human c-Rel, we isolated cyclin E, the regulatory subunit of the Cdk2 complex, as a c-Rel-binding protein. These findings support and provide physical basis for the involvement of NF-kappa B in the G1/S-phase cell cycle control, and suggest an important role played by the C-terminal sequence of c-Rel.
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The inactivation of the prototype NF-kappaB inhibitor, IkappaBalpha, occurs through a series of ordered processes including phosphorylation, ubiquitin conjugation, and proteasome-mediated degradation. We identify valosin-containing protein (VCP), an AAA (ATPases associated with a variety of cellular activities) family member, that co-precipitates with IkappaBalpha immune complexes. The ubiquitinated IkappaBalpha conjugates readily associate with VCP both in vivo and in vitro, and this complex appears dissociated from NF-kappaB. In ultracentrifugation analysis, physically associated VCP and ubiquitinated IkappaBalpha complexes sediment in the 19 S fractions, while the unmodified IkappaBalpha sediments in the 4.5 S fractions deficient in VCP. Phosphorylation and ubiquitination of IkappaBalpha are critical for VCP binding, which in turn is necessary but not sufficient for IkappaBalpha degradation; while the N-terminal domain of IkappaBalpha is required in all three reactions, both N- and C-terminal domains are required in degradation. Further, VCP co-purifies with the 26 S proteasome on two-dimensional gels and co-immunoprecipitates with subunits of the 26 S proteasome. Our results suggest that VCP may provide a physical and functional link between IkappaBalpha and the 26 S proteasome and play an important role in the proteasome-mediated degradation of IkappaBalpha.
An ovary-specific cystatin is immunocytochemically demonstrated to be localized in the chorions, cortical granules, and yolk granules of carp oocytes, as well as in the follicle cells surrounding oocytes. During cortical reaction, cystatin is exocytosed from cortical granules into the perivitelline space. In situ hybridization confirms that cystatin is synthesized by oocytes and follicle cells. Western blotting reveals that chorion cystatin appears in multiple bands of high molecular weight (from 65 kDa to larger than 200 kDa). No cystatin monomer of 14 kDa is found. These results indicate that chorion cystatin is conjugated with other chorion components. Two forms of conjugates are found. In one form, cystatin, ZP2, fibroin-like substance (FLS), and cathepsin-like substance (CLS) are conjugated, which is extracted by sodium dodecyl sulfate. In the other form, cystatin, FLS, and CLS are conjugated, which is extracted by guanidine thiocyanate (GTC). Most chorion cystatin of oocytes and ovulated eggs is solubilized by GTC, while a large amount of cystatin remains in the fertilization envelope of cortical reacted eggs after extraction by GTC.
To report the in vitro antibiotic susceptibility of Campylobacter species, we determined the MICs of 6 antibiotics by E-test for 93 human clinical strains and 35 chicken strains. The 6 antimicrobial agents tested were gentamicin, erythromycin, clindamycin, tetracycline, ciprofloxacin, and nalidixic acid. Isolates from humans were significantly more susceptible than chicken strains to erythromycin, clindamycin and ciprofloxacin. Nearly all of the human and chicken strains were susceptible to gentamicin. Among human isolates of C. jejuni, cross-resistance between nalidixic acid and ciprofloxacin was found in 66% of the strains, but none of the nalidixic acid-susceptible strains was resistant to ciprofloxacin. The higher prevalence of ciprofloxacin resistance in this area may be attributable to the large amount use of quinolones in poultry. Because of the high resistance rates of chicken isolates to the commonly used antimicrobial agents, it is necessary to create innovative methods to limit the inappropriate use of antibiotics in poultry in order to prevent the spread of the drug-resistant strains to humans.
BACKGROUND: Fungi are common pathogens of nosocomial infections in the very low birth weight (VLBW) infants. The purpose of this study was to investigate the fungal colonization rate in VLBW infants and the association between fungal colonization and systemic fungal diseases. MATERIALS: Between January 1, 1996, and December 31, 1996, 116 infants with birth weight < 1500 g admitted to the neonatal intensive care unit of Chang Gung Children's Hospital in the first day of life were included in this prospective study. METHODS: Cultures from oropharynx, rectum, skin (groin and axilla), bag urine and endotracheal aspirates were obtained in the first 24 h after birth and weekly thereafter throughout their neonatal intensive care unit stay. Medical records were reviewed weekly. RESULTS: Fungal colonization was detected in 25 infants, among whom 17 infants developed colonization by 2 weeks of life. Candida albicans (61%) and Candida parapsilosis (29%) were the 2 most common organisms. The rectum (76%) was the most frequent site of colonization. Factors significantly associated with colonization were prolonged administration of antibiotic therapy, parenteral nutrition and intralipid emulsion. Three of 116 infants developed fungemia. The association between colonization and subsequent fungemia was demonstrated in 1 infant, representing 4% of colonized infants. CONCLUSION: Fungal colonization was detected in one-fifth of VLBW infants and represents a risk factor for fungemia. Because disease occurred in the absence of apparent colonization, factors other than colonization may contribute to invasive candidiasis.
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Acute suppurative thyroiditis (AST) is a rare disorder. The rarity of AST is a result of the resistance of the thyroid gland to local infection. Thyroid function tests are usually normal in AST. In a review of the literature from 1966 to 1995, only three cases of AST associated with thyrotoxicosis have been convincingly demonstrated. The thyrotoxicosis in these cases was caused by diffuse inflammation of the thyroid gland and to the disruption of follicles with the release of pre-formed thyroid hormone into the circulation. Thus, the thyrotoxicosis in these cases was transient. With successful therapy, nearly all patients showed complete recovery of thyroid function within two to three months. The patient in the case here was a diabetic woman with Graves' disease in whom thyrotoxicosis occurred after Klebsiella pneumoniae thyroiditis, with relapse nine months after discharge. Thus, the patient's thyrotoxicosis might not have been caused simply from thyroid tissue destruction by AST, but also as a result of enhancing autoimmune activity. No previous case has ever been reported in the English literature. In diabetics, the impairment of chemotaxis and phagocytosis has been noted. Therefore, diabetes mellitus (DM) might have been the precipitating factor for this patient's acquiring this unusual infection. Thyrotoxicosis and AST will increase insulin requirements and thus aggravate diabetes. In addition, poor control of blood sugar will enhance the severity of AST.
The genetic elements and regulatory mechanisms responsible for human interleukin 9 (IL-9) gene expression in a human T cell leukemia virus type I-transformed human T cell line, C5MJ2, were investigated. We demonstrated that IL-9 gene expression is controlled, at least in part, by transcriptional activation. Transient expression of the luciferase reporter gene linked to serially deleted sequences of the 5'-flanking region of the IL-9 gene has revealed several positive and negative regulatory elements involved in the basal and inducible expression of the IL-9 gene in C5MJ2 cells. An AP-1 site at -146 to -140 was shown to be involved in the expression of the IL-9 gene. A proximal region between -46 and -80 was identified as the minimum sequence for the basal and inducible expression of the IL-9 gene in C5MJ2 cells. Within this region, an NF-kappaB site at -59 to -50 and its adjacent 20-base pair upstream sequence were demonstrated to play a critical role for the IL-9 promoter activity. DNA-protein binding studies indicated that NF-kappaB, c-Jun, and potentially novel proteins (around 35 kDa) can bind to this important sequence. Mutations at different sites within this proximal promoter region abolished the promoter activity as well as the DNA binding. Taken together, these results suggest that the cooperation of different transcription factors is essential for IL-9 gene expression in T cells.
Poly-2'-O-(2,4-dinitrophenyl)poly[A] (DNP-poly[A] is a potent inhibitor of reverse transcriptases from a variety of sources (I. Kang and J. H. Wang, J. Biol. Chem. 269:12024-12031, 1994). In the present study, its inhibitory effect on the reverse transcriptase (RT) from Moloney murine leukemia virus (MuLV) was investigated. DNP-poly[A] was found to enter the virus spontaneously and to completely inhibit the RT within 30 min at 0 degree C. The inhibitor was also spontaneously transported into isolated human lymphocytes and leukocytes at 37 degrees C. Animal studies have demonstrated the effectiveness of DNP-poly[A] as an antiviral drug when administered intraperitoneally at various doses from 1 to 100 mg/kg of body weight. MuLV-infected mice show the presence of RT in their blood as well as increased numbers of leukocytes. After the administration of DNP-poly[A] at a dosage of 100 mg/kg of body weight three times a week over a 3-week period, RT could no longer be detected by an ultrasensitive RT-PCR assay. Autopsy showed that the spleens of infected but untreated mice were enlarged 2- to 10-fold, with fused nodules and the proliferation of large abnormal lymphocytes, whereas the spleens of infected but treated mice resembled the normal spleens of uninfected control mice. These observations indicate that further study of DNP-poly[A] as a general antiretroviral agent is desirable.
The DNA profiles of two unrelated individuals can match (complete similarity) by chance alone. When the two individuals are related, the probability of a coincidental match is higher. Here, I deal with the probabilities of coincidental matches for both related and unrelated individuals. The derivation starts from first principles; no prior knowledge is required. The results obtained by the method developed here are compared with some other methods.