PubMed Health⌕ Search

Biomedical subjects

H L Hsu

Publications and source records attributed to H L Hsu.

At least 19 recordsLinked to original sources

Extensive cerebrospinal fluid enhancement following gadolinium chelate administration: possible pathogenesis.

Diffuse cerebrospinal fluid (CSF) enhancement following gadolinium administration is a rarely recognized phenomenon, and its mechanism is not fully understood. We report two cases of diffuse CSF enhancement following gadolinium administration and review the literature. We conclude that the contributing factors of this phenomenon include blood-CSF barrier disruption, increased dosage, impair renal clearance, delayed imaging after contrast administration, and use of different pulse sequences.

Artifacts↗

Primary intracranial myxopapillary ependymomas: report of two cases and review of the literature.

Myxopapillary ependymoma is a variant of ependymoma occurring almost exclusively in the conus medullaris or filum terminale. Myxopapillary ependymoma found primarily in the brain is extremely rare. Two such cases appearing at the 4th ventricle and cerebral falx are reported. The imaging features of such tumors are a primary cystic mass with strong enhancement at its solid part. Myxopapillary ependymoma should be a possible differential diagnosis when an intracranial cystic tumor is found.

Adult↗

Empirical monotherapy with meropenem in serious bacterial infections in children.

The efficacy and safety profile of meropenem were analyzed according to data collected from hospitalized pediatric patients aged 4 days to 20 years who had serious bacterial infections and were treated in a major teaching hospital in Taipei. Of the 53 patients enrolled, 47 were analyzed for clinical efficacy and 53 for safety. The satisfactory clinical response rate was 57% in lower respiratory tract infection, 58% in septicemia, 100% in complicated urinary tract infection, osteomyelitis, and central nervous system infection, 83% in skin and soft tissue infection, and 93% in intra-abdominal infection. Eleven (21%) patients experienced adverse events related to meropenem. The most commonly observed adverse reactions were elevated hepatic enzymes (7.5%), increased alkaline phosphatase (3.8%), and thrombocytosis (3.8%). There was no meropenem-related seizure, withdrawal, or death. The results of this study suggested that meropenem is well tolerated even in young infants, and is effective in treating serious childhood bacterial infection. However, this study also identified a proportion of hospitalized pediatric patients with isolates that were resistant to meropenem. The trends in meropenem resistance among nosocomially acquired bacteria should be monitored closely.

Adult↗

Ku acts in a unique way at the mammalian telomere to prevent end joining.

Telomeres are specialized DNA/protein structures that act as protective caps to prevent end fusion events and to distinguish the chromosome ends from double-strand breaks. We report that TRF1 and Ku form a complex at the telomere. The Ku and TRF1 complex is a specific high-affinity interaction, as demonstrated by several in vitro methods, and exists in human cells as determined by coimmunoprecipitation experiments. Ku does not bind telomeric DNA directly but localizes to telomeric repeats via its interaction with TRF1. Primary mouse embryonic fibroblasts that are deficient for Ku80 accumulated a large percentage of telomere fusions, establishing that Ku plays a critical role in telomere capping in mammalian cells. We propose that Ku localizes to internal regions of the telomere via a high-affinity interaction with TRF1. Therefore, Ku acts in a unique way at the telomere to prevent end joining.

Animals↗

In vitro and in vivo suppression of growth of rat liver epithelial tumor cells by antisense oligonucleotide against protein kinase C-alpha.

BACKGROUND/AIMS: It has been hypothesized that liver stem cells may be activated and proliferate upon liver injury and may participate in the development of liver cancer. GP7TB, a rat liver epithelial tumor cell line, possesses characteristics of liver stem-like cells and can develop into a tumor in syngeneic Fischer 344 rat. We found that protein kinase C-alpha (PKC-alpha) is overexpressed in GP7TB cells. The importance of PKC-alpha for this liver tumor cell was elucidated. METHODS: Antisense oligonucleotide (ODN) was applied to suppress the production of PKC-alpha in GP7TB cells in vitro and in vivo. Cell viability was measured by acid phosphatase assay. The cellular levels of PKC-alpha and Bcl-2 were monitored by Western-blot analysis. Activation of nuclear factor NF-kappaB was analyzed by electrophoretic mobility shift assay. Cell cycle phase distribution was monitored by FACScan. Cell apoptosis was detected by TUNEL assay and histochemical staining of tumor tissue sections. The in vivo experiment was conducted by implanting tumor mass of GP7TB in the liver of F-344 rat and continuous delivery of the ODN by a mini-osmotic pump. RESULTS: Antisense ODN effectively suppressed the level of PKC-alpha that resulted in the decrease of Bcl-2 and nuclear NF-kappaB. The cumulative viable cells also decreased dramatically for the antisense-treated group. FACScan showed that the cells were arrested at early S-phase. These cells in turn went into apoptosis without completing a cell cycle. It was found that growth of the tumor was suppressed efficiently by antisense ODN. Cell apoptosis was found in the orthotopic tumor. The normal liver cells were not affected. CONCLUSIONS: A lethal effect of depressing the level of PKC-alpha in GP7TB cells and success in suppressing orthotopic tumor growth in vivo suggests that PKC-alpha antisense ODN would be a promising therapeutic agent for some liver cancers.

Acid Phosphatase↗

Enteric adenovirus infection in children in Taipei.

Enteric adenoviruses (EAds), including type 40 (Ad40) and 41 (Ad41), can cause acute and severe diarrhea in young children. To delineate the epidemiological features of pediatric EAds infection in Taiwan, we conducted a retrospective study of all cases of EAds gastroenteritis in children treated at National Taiwan University Hospital for the period from July 1993 to December 1997. Stool samples were tested for the presence of Ad40 or Ad41 by enzyme immunoassay (EIA). A total of 64 cases of EAds infection in 63 children aged from 8 days to 81 months old with a median age of 9.5 months treated during the study period were identified. The male-to-female ratio was 1.63 (39/24). No obvious seasonal clustering of EAds cases was noted. Most patients (76.6%) were infected before the age of 2 years. Clinical features included diarrhea (96.9%), fever (54.7%), vomiting (45.3%), mild dehydration (43.8%), symptoms of upper respiratory tract infection (21.9%), and abdominal pain (12.5%). Analysis of fecal samples in patients with diarrhea showed watery diarrhea in 72.2%, diarrhea with mucus in 20%, diarrhea with blood in 3.1% and diarrhea with mucus and blood in 1.6 % of all patients. Nearly one-half (43.5%) of the patients had diarrhea for more than 7 days. Thirty-seven patients (57.8%) were hospitalized due to gastroenteritis or other unrelated diseases, and 11 patients (17.2%) acquired enteric adenovirus infection during hospitalization for other underlying disease. Twelve patients (18.8%) had mixed infections, which included rotavirus, respiratory syncytial virus (RSV) and Salmonella species. There were no deaths in this series. The findings of this study suggest that EAds are important etiologic microbes of pediatric gastroenteritis.

Adenoviridae Infections↗

Rotavirus gastroenteritis in children: 5-year experience in a medical center.

Rotavirus infection is the leading cause of childhood gastroenteritis. We retrospectively reviewed cases of rotavirus gastroenteritis at National Taiwan University Hospital from January 1993 to December 1997. During the study period there were 429 patients with rotavirus infection with ages ranging from 1 day to 16 years with a median of 13 months. The male-to-female ratio was 1.2:1. Infection occurred before the age of 2 years old in 76% of patients. The seasonal peak occurred in the late winter and early spring during 1993 to 1996, but the case number increased in late spring and summer in 1997. The G serotype of the rotavirus was identified in 302 patients (70%). Vomiting and dehydration developed more frequently following infection with G1 rotaviruses, while an increased frequency of seizures was noted following G2 infection; the differences were not statistically significant. One patient had two episodes of infection; the first one was caused by G1 rotavirus, and the strain causing the second infection could not be typed. In conclusion, the results suggest that there is a strong seasonal variation in the incidence and characteristics of rotavirus infection in Taipei area. The infections caused by G1 and G2 rotaviruses were clinically indistinguishable.

Adolescent↗

Ku is associated with the telomere in mammals.

Telomeres are specialized DNA/protein complexes that comprise the ends of eukaryotic chromosomes. The highly expressed Ku heterodimer, composed of 70 and 80 K(d) subunits (Ku70 and Ku80), is the high-affinity DNA binding component of the DNA-dependent protein kinase. Ku is critical for nonhomologous DNA double-stranded break repair and site-specific recombination of V(D)J gene segments. Ku also plays an important role in telomere maintenance in yeast. Herein, we report, using an in vivo crosslinking method, that human and hamster telomeric DNAs specifically coimmunoprecipitate with human Ku80 after crosslinking. Localization of Ku to the telomere does not depend on the DNA-dependent protein kinase catalytic component. These findings suggest a direct link between Ku and the telomere in mammalian cells.

Animals↗

Isolation of Ku70-binding proteins (KUBs).

DNA-dependent protein kinase (DNA-PK) plays a critical role in resealing DNA double-stand breaks by non-homologous end joining. Aside from DNA-PK, XRCC4 and DNA ligase IV, other proteins which play a role(s) in this repair pathway remain unknown; DNA-PK contains a catalytic subunit (DNA-PKcs) and a DNA binding subunit (Ku70 and Ku80). We isolated Ku70-binding proteins (KUB1-KUB4) using yeast two-hybrid analyses. Sequence analyses revealed KUB1 to be apolipoprotein J (apoJ), also known as X-ray-inducible transcript 8 (XIP8), testosterone-repressed prostate message-2 (TRPM-2) and clusterin. KUB2 is Ku80. KUB3 and KUB4 are unknown, >10 kb trans-cripts. Interactions of apoJ/XIP8 or KUB3 with Ku70 were confirmed by co-immunoprecipitation analyses in MCF-7:WS8 breast cancer or IMR-90 normal lung fibroblast cells, respectively. The interaction of apoJ/XIP8 with Ku70 was confirmed by far-western analyses. Stable over-expression of full-length apoJ/XIP8 in MCF-7:WS8 caused decreased Ku70/Ku80 DNA end binding that was restored by apoJ/XIP8 monoclonal antibodies. The role of apoJ/XIP8 in ionizing radiation resistance/sensitivity is under investigation.

Animals↗

Effects of various chemical sterilization methods on the crosslinking and enzymatic degradation characteristics of an epoxy-fixed biological tissue.

Due to the nature of bioprostheses, which are mainly biological tissues that cannot be sterilized with heat or irradiation, the sterilization method by choice is generally liquid chemicals. It is known that a number of liquid chemicals can have rapid germicidal effect and can be used to sterilize bioprostheses. The study was to evaluate the effects of various chemical sterilization methods on the crosslinking and enzymatic degradation characteristics of an epoxy-fixed biological tissue. The chemical sterilants employed were: a 70% ethanol solution (EtOH), a 2% epoxy compound + 20% ethanol solution (EX-810), a 2% propylene oxide + 20% ethanol solution (PO), and a 0.625% glutaraldehyde + 20% ethanol + 0.2% polysorbate solution (GA). Both masking and crosslinking of the free amino groups within the epoxy-fixed tissue were observed subsequent to sterilization with GA or EX-810. This improved the resistance of the GA or EX-810 sterilized tissues against collagenase degradation as compared to its nonsterilized counterpart. However, subsequent to sterilization with PO, only masking of the free amino groups within the epoxy-fixed tissue was noted. The inhibition of the collagenase degradation by masking of the free amino groups was traded off by the more random molecular packing of the PO sterilized sample due to the introduction of the side branches. Sterilization of the epoxy-fixed tissue with EtOH may increase its denaturation temperature and tensile strength, while neither masking nor crosslinking of free amino groups within the tissue took place. The resistance to degradation of the EtOH sterilized tissue, however, did not improve as compared to its nonsterilized counterpart.

Bioprosthesis↗

Degradation potential of biological tissues fixed with various fixatives: an in vitro study.

The purpose of this study was to investigate the in vitro degradation potential of porcine pericardia fixed with various aldehyde or epoxy compound (EC) fixatives, using bacterial collagenase and pronase. The fixatives investigated were formaldehyde (FA), glutaraldehyde (GA), monofunctional EC (EX-131), and multifunctional ECs (EX-810, EX-313, and EX-512). Fresh porcine pericardium was used as a control. The test samples were well immersed in a 20-U/mL collagenase solution or a 10-U/mL pronase solution and incubated at 37 degrees C at pH 7.5 for 24 h. The extent of degradation of each test sample was determined by measuring its increment in free amino group content and changes in collagen structure, denaturation temperature, and tensile stress after degradation. In general, the extent of tissue degradation with pronase was more notable than with collagenase. As observed with fresh tissue, the EX-131 EC fixed tissue radically disintegrated after either collagenase or pronase degradation, whereas the other test samples remained intact. The reason for this may reside in the more random molecular packing of the EX-131 EC-fixed tissue, which led to some loss in its helical integrity. This made penetration of enzymes into biological tissue easier. Of the multifunctional EC test groups, tissues fixed with tetrafunctional EC (EX-521) or trifunctional EC (EX-313) had relatively better resistance to degradation than those fixed with bifunctional EC (EX-810). The extent of degradation for the EX-313 or EX-512 EC fixed tissues was similar to that observed for the FA- or GA-fixed tissues. The results of this study indicated that the biological tissue fixed with monofunctional EC (EX-131) cannot resist bacterial collagenase or pronase degradation. However, resistance to degradation of the multifunctional EC (EX-313 or EX-152)-fixed tissues was comparable to that of the aldehyde (FA or GA)-fixed tissues. Therefore, of various EC fixatives, the EC with a greater number of functional groups should be chosen for tissue fixation to increase its resistance to enzymatic degradation.

Amino Acids↗

Antisense oligodeoxynucleotides of IGF-II selectively inhibit growth of human hepatoma cells overproducing IGF-II.

Insulin-like growth factor II (IGF-II) is expressed in many developing embryonic tissues and is involved in mammalian growth and development. After birth, serum IGF-II is mainly produced by liver cells. Many reports have indicated that IGF-II is overexpressed in some hepatocellular carcinoma (HCC) tissue. These findings imply the possible importance of this growth factor in carcinogenesis. We screened four human HCC cell lines and three rat HCC cell lines and found that HuH-7 and HepG2 cells produced fivefold more intracellular IGF-II than the other cell lines. Experimental data indicate that IGF-II functions through the intracrine mode for HuH-7 cells. To study whether the overexpression of IGF-II is significant for the growth of HCC or only a consequence of HCC development, we used antisense oligodeoxynucleotides (ATON) to arrest the translation of IGF-II mRNA, and then measured the effects on cell growth. We found that the production of IGF-II was suppressed by ATON, and the decrease of IGF-II resulted in growth inhibition of HuH-7 and HepG2. ATON had no effect on the other tested cell lines, which produced lower levels of IGF-II. The growth inhibition was mainly attributed to a decrease of cell proliferative activity. The results indicate that the IGF-II-overproducing cell lines do depend on IGF-II for growth, and ATON of IGF-II can selectively inhibit the growth of these cells. ATON may be a potential therapeutic agent for this type of HCC in vivo.

Animals↗

Fixation of various porcine arteries with an epoxy compound.

The clinical results of biological vascular grafts have been unsatisfactory. The poor results of these vascular grafts may be attributed to the fixatives, aldehydes, used in fixing tissues. In an attempt to overcome this problem, a new fixative, epoxy compound, has recently been used to fix biological vascular grafts. The study was undertaken to investigate the crosslinking characteristics, fixation index and denaturation temperature, of various porcine arteries fixed with an epoxy compound. The porcine arteries investigated in the study were the common carotid artery, internal thoracic artery, abdominal aorta, and saphenous artery. In addition, the effects of sonication on the porcine arteries before fixation on their crosslinking characteristics were analyzed. The fresh and glutaraldehyde-fixed arteries were used as controls. It was noted that glycine, proline, and alanine were the most abundant amino acids found in the porcine internal thoracic artery. In the amino acid analysis, it was observed that the amino acids in the porcine arteries reacted with epoxy compound or glutaraldehyde were lysine, hydroxylysine, histidine, and arginine. Of these amino acids, lysine was the most reactive. In general, the fixed arteries were relatively stiffer than their fresh counterparts. The fixation indices and denaturation temperatures of various porcine arteries were comparable throughout the entire fixation process. The amounts of free amino groups of the sonicated arteries were significantly lower than those of their unsonicated counterparts (p < 0.05). It is speculated that the diminishing free amino groups of the sonicated arteries may be attributed to the removal of the destroyed cell debris and adherent proteins of the arteries after sonication. However, it was learned that sonication on the porcine arteries before fixation did not seem to affect their fixation indices and denaturation temperatures. The results obtained in this study may help one in selecting the raw materials for developing a small-diameter biological vascular graft

Analysis of Variance↗

In vitro study of enzymatic degradation of biological tissues fixed by glutaraldehyde or epoxy compound.

The study, using bacterial collagenase, was to investigate the changes in characteristics of a collagen-rich tissue, porcine pericardium, fixed by glutaraldehyde or epoxy compound (ethylene glycol diglycidyl ether) during the course of degradation. Fresh porcine pericardium was used as a control. During degradation, the heat released by the reaction of collagenase with a test sample was monitored by a highly sensitive microcalorimeter. Also, the degree of degradation of each test sample was determined by measuring its increment in free amino group content and changes in denaturation temperature and tensile strength. Microcalorimetric analysis of collagenase degradation of fresh, epoxy-fixed, and glutaraldehyde-fixed tissues revealed that the heat released during degradation correlates well with the degree of tissue degraded. The cleaving of peptide bonds in biological tissue by collagenase degradation may increase its free amino group content and reduce its denaturation temperature and tensile strength. It was noted that the fresh tissue cannot resist bacterial collagenase degradation, while the glutaraldehyde-fixed tissue had a relatively better resistance to degradation than its epoxy-fixed counterpart.

Animals↗

Partial DiGeorge anomaly associated with 10p deletion.

We report a girl with partial DiGeorge anomaly associated with a distal chromosome 10p deletion. The initial manifestation was hypocalcemia convulsion at the age of 14 days. The patient was small for her gestational age and showed symptoms of poor feeding and inspiratory stridor. Facial dysmorphisms included a cupped ear, hypertelorism downslanted and short palpebral fissures frontal bossing, anteverted nostrils, a flat nasal bridge, and micrognathia. Developmental delay was also noted. Hypoplasia of the thymus was detected by ultrasound examination, but results of immunologic studies were all normal at 6 weeks of age. The echocardiogram, brain ultrasound, electroencephalogram, and magnetic resonance images of the brain were normal, but brainstem auditory evoked potentials showed bilateral sensorineural hearing loss. Chromosomal analysis showed 16, XX, del(10)(p12.3); the parents had normal karyotypes. After treatment with vitamin D, calcium gluconate, and magnesium sulfate, the patient's serum calcium and magnesium levels were within normal limits. She was discharged and received regular follow-up at our clinic for physical therapy and to ensure adequate supply of divalent cations. Complex partial seizure was noted at the age of 1 year and was controlled with carbamazepine. To our knowledge, this is the first Taiwanese reported to have partial DiGeorge anomaly associated with 10p deletion. We recommend that standard karyotyping should be performed in children suspected to have this anomaly.

Chromosome Deletion↗

Studies on epoxy compound fixation.

Bioprostheses derived from collagenous tissues have to be fixed and subsequently sterilized before they can be implanted in humans. Clinically, the most commonly used fixative is glutaraldehyde. However, the tendency for glutaraldehyde to markedly alter tissue stiffness and promote tissue calcification are well-recognized drawbacks of this fixative. To address the deficiencies with the glutaraldehyde-fixed tissue, a new fixative, epoxy compound, was used to fix biological prostheses. The study was undertaken to investigate the fixation rates and crosslinking densities of biological tissues fixed with various epoxy compounds. These epoxy compounds are different in their chemical structures. Glutaraldehyde was used as a control. The fixation rates and crosslinking densities of the fixed tissues were determined by measuring their fixation indices and denaturation temperatures, respectively. Generally, the epoxy-fixed tissues were more pliable than the glutaraldehyde-fixed one. Furthermore, the tissues fixed with monofunctional epoxy compound were more pliable than those fixed with multifunctional epoxy compounds. With increasing pH or temperature, the fixation rate of epoxy compound increased. However, the number of epoxide functional groups did not seem to affect the fixation rate of the epoxy compound. The fixation rate of glutaraldehyde was faster than that of epoxy compounds. Additionally, the crosslinking density of the glutaraldehyde-fixed tissue was greater than that of the epoxy-fixed counterparts. Moreover, it was noted that the denaturation temperatures of the tissues fixed with glutaraldehyde or multifunctional epoxy compounds were significantly higher than the fresh ones (p < 0.05), while that fixed with monofunctional epoxy compound stayed roughly the same throughout the entire fixation process (p > 0.05). The results obtained in this study may be used to optimize the fixation process for developing bioprostheses fixed with epoxy compounds.

Animals↗

Cross-linking characteristics of biological tissues fixed with monofunctional or multifunctional epoxy compounds.

The cross-linking characteristics of biological tissues fixed by various epoxy compounds with different chemical structures (i.e. number of epoxide functional groups and backbone length) were investigated. Generally speaking, the tissues fixed with monofunctional fixatives were more pliable than those fixed with multifunctional fixatives. The fixation indices of the fixed tissues did not seem to be affected by the chemical structures of the fixatives. However, the number of functional groups and backbone length of the fixatives did play an important role in influencing the denaturation temperatures of the fixed tissues. In general, the denaturation temperatures of the multifunctional fixed tissues were higher than those of the monofunctional fixed tissues. Among the monofunctional fixed tissues, it was found that increasing the backbone length of the fixative decreased the denaturation temperature of the fixed tissue. This effect was present until the backbone length of the fixative became large enough.

Animals↗

Evaluation of an epoxy-fixed biological patch with ionically bound heparin as a pericardial substitute.

In an attempt to develop an improved pericardial substitute, we undertook the development of an epoxy-fixed biological patch with ionically bound heparin. The study was to evaluate the cross-linking characteristics of this newly developed biological patch using its glutaraldehyde-fixed counterpart as a control. In addition, the feasibility of using this newly developed biological patch as a pericardial substitute was assessed in a canine model. In the study, it was observed that the epoxy-fixed biological patch appeared more similar to the native pericardium in colour and was more pliable than its glutaraldehyde-fixed counterpart. Also, both the epoxy- and glutaraldehyde-fixed biological patches had significant increases in fixation index and denaturation temperature as compared to the fresh one (p < 0.05). In the canine study, the epoxy-fixed biological patch with ionically bound heparin was found to have significantly less adhesion formation than those currently used clinically (p < 0.05).

Analysis of Variance↗