Search PubMed⌕ Search

Biomedical subjects

C H Hu

Publications and source records attributed to C H Hu.

At least 37 records · Page 2Linked to original sources

Characterization of acute myeloid leukemia with MLL rearrangements--no increase in the incidence of coexpression of lymphoid-associated antigens on leukemic blasts.

MLL gene rearrangements are associated with coexpression of myeloid- and lymphoid-associated antigens on leukemic blasts and a dismal outcome in acute lymphoblastic leukemia (ALL). Whether the same conditions can apply to acute myeloid leukemia (AML) is not quite clear. Rearrangements of the MLL gene were analyzed on 113 patients with newly diagnosed de novo AML in a single institution. Sixteen (14%) of them showed rearranged bands by Southern blot analysis, including three (50%) of six infants, three (14%) of 21 children between 1 and 15 years and 10 (12%) of 86 adults. MLL rearrangements were not only detected in M5 (four of 12 patients, 33%) and M4 (six of 31, 19%) subtypes but also in other non-M4-M5 AML (six of 70, 9%), including M1, M2 and M7, but not M3 subtype. Seven patients had chromosomal abnormalities involving 11q23, but nine did not. The latter comprised three (6%) of 48 patients with normal karyotype, one with t(8;21), none with t(15;17), inv(16) or t(9;22), and four (15%) of 27 with cytogenetic aberrations other than those specific structural abnormalities. In contrast to ALL, AML patients with MLL rearrangements did not tend to coexpress lymphoid- and myeloid-associated antigens simultaneously on leukemic blasts and have similar outcome as those without the gene rearrangements.

Acute Disease↗

Development of fungal mycelia as skin substitutes: effects on wound healing and fibroblast.

In this study, Sacchachitin membrane, prepared from the residue of the fruiting body of Ganoderma tsugae, was estimated for its effects on wound healing and the proliferation and migration of fibroblast cells. Two mirror-image wounds were made on the back of female guinea pigs by dissecting a 1.5 x 1.5 cm2 skin surface of full thickness. Sacchachitin membrane was placed randomly on one of the wounds and gauze or Beschitin on the other. Changes in the wound area were measured and photographed after a predetermined amount of time postoperatively. Histological examination of the wound and surrounding tissue was also performed to reveal any interaction of tissue with the dressing. The results showed that the wound area covered with Sacchachitin membrane was statistically smaller than that covering with gauze on day 10, whereas there was no significant difference in the wound size compared to that with Beschitin. Fibroblast cells from the dermis layer of guinea pigs were used. The number of fibroblast cells were counted on the predetermined days in the culture suspended with or without 0.01% w/v dressing materials. By layering on DMEM plates, the number of fibroblast cells migrating across the center line or outside of the central hole were counted after five days. All the results indicated that both 0.01% w/v of Sacchachitin and chitin significantly enhanced the proliferation and migration of fibroblast cells.

Animals↗

Minimally differentiated acute myeloid leukemia in Taiwan: predominantly occurs in children less than 3 years and adults between 51 and 70 years.

Acute myeloid leukemia (AML) with minimal differentiation was usually referred to as acute undifferentiated leukemia in the past. With the help of immunophenotyping, this subtype of leukemia was shown to express myeloid antigens on the blasts and was designated AML-M0 by FAB Cooperative Study Group in 1991. Among the 423 consecutive newly diagnosed de novo AML at our institution, 12 (2.8%) were of M0 subtype. The proportion of M0 in AML was higher in children than in adults (8.2% vs 1.7%). Four other M0 patients referred from outside hospitals for immunophenotyping were also included in this study. There were two peaks in age distribution of these 16 patients: less than 3 years and between 51 and 70 years, respectively. Organomegaly was more common in patients with AML-M0 than in those with other subtypes (56.3% vs 29.2%, P = 0.025). The former patients had higher incidences of CD7 and CD34 expression on the leukemic cells than the latter ones (50% vs 16.9%, P = 0.003 and 69.2% vs 37.9%, P = 0.019, respectively). The patients with AML-M0 showed more frequent clonal chromosomal abnormalities in the leukemic cells than other AML patients (83.3% vs 53.9%, P = 0.039); the same is also true for complex cytogenetic aberrations (50% vs 11. 4%, P = 0.004). Adults with AML-M0 showed a lower complete remission (CR) rate and significantly poorer survival than those with non M0-AML. However there was no significant difference in outcome between the two groups of pediatric patients. In conclusion, AML-M0 is a unique subtype of leukemia that has distinct age distribution and shows different clinical and biological characteristics from other AML. Adult patients have poor prognosis. Whether pediatric patients had better outcome than adults needs to be clarified in further studies.

Acute Disease↗

The first high-mobility-group box of upstream binding factor assembles across-over DNA junction by basic residues.

Upstream binding factor (UBF) is a eukaryotic RNA polymerase I-specific transcription factor. Its predominant DNA-binding motif, ubfHMG box 1, preserves DNA assembling activity that can bind two or more DNA duplexes simultaneously to form a crossover DNA junction. Here we investigate the basis of crossover DNA-assembling activity of ubfHMG box 1 by extensive mutagenesis analyses and mobility shift assay. Although the ubfHMG box 1 preserves a high mobility group (HMG) core structure, changing a number of the consensus hydrophobic and aromatic residues to alanine did not inhibit its crossover-assembling activity. This indicates that these residues do not directly participate in protein-DNA interaction. However, altering a series of basic residues in the helices 1 and 2 regions or the N-terminal extended strand of the ubfHMG box 1 motif had severe effects on DNA-assembling activity; however, certain non-specific DNA binding activity still remained. This suggests that the ubfHMG box 1 motif might extensively contact the backbone of a crossover junction through its multiple basic residues. Mutating a hydrophobic residue in the terminal dimerization domain inhibited the association of truncated Xenopus UBF, but had little effect on its crossover-assembling activity. This indicates that the UBF-crossover DNA complex is not established by the association of individual DNA-bound peptides.

Amino Acid Sequence↗

Differential effects of heavy metals on the binding of Xenopus upstream binding factor(xUBF) to DNA.

Xenopus upstream binding factor (xUBF) is a transcription factor for RNA polymerase I which contains multiple DNA-binding motifs. Among these DNA-binding motifs, HMG box I is essential for promoting RNA polymerase I-dependent rRNA gene transcription. Gel shift assay indicated that the binding of recombinant HMG box I to a 136-bp linear DNA probe was significantly inhibited by Cd2+ at 1 microM. The formation of larger protein-DNA complexes was particularly sensitive to Cd2+. The interaction between HMG box I and DNA was completely inhibited by 10 microM of Cd2+, yet this interaction was not inhibited by the same concentration of Ca2+. Hg2+ at 0.1 microM began to cause abnormal band shifting, and protein-DNA bands disappeared to the wells of a polyacrylamide gel in the presence of 10 microM of Hg2+, reflecting that a drastic change in the conformation of HMG box I-DNA had occurred. The binding of HMG box I to DNA was slightly disturbed by As3+ at 1 microM and was significantly affected at 10 microM. Our results suggest that inhibition of the normal binding of UBF to its target DNA may be one of the mechanisms of heavy metal-induced inhibition of RNA synthesis.

Animals↗

Fungal mycelia as the source of chitin and polysaccharides and their applications as skin substitutes.

A wovenable skin substitute (Sacchachitin) made from the residue of the fruiting body of Ganoderma tsugae was developed in this study. Chemical analysis revealed that the treated residue was a copolymer of beta-1,3-glucan (ca 60%) and N-acetylglucosamine (ca 40%) with a filamental structure of mycelia form, as demonstrated by both optical and scanning electron microscopy. The pulp-like white residue was then woven into thin, porous sheets 7.0 cm in diameter and 0.1-0.2 mm in thickness by filtration and lyophilized for use as a skin substitute. The wound area produced by dissecting rat skin of full thickness was found to almost completely heal on the side covered with Sacchachitin, whereas the control side covered with cotton gauge was around 6.0 cm2 on the 28th day. Furthermore, the wound healing effects of the chitin sheet from crab shell (Beschitin) and Sacchachitin were not found to be significantly different.

Acetylglucosamine↗

The dimerization domain upstream binding factor contains multiple helical structures.

The upstream binding factor, UBF, is an RNA polymerase I transcription factor which contains multiple DNA binding domains and a novel protein dimerization domain. Active UBF forms homodimers in vivo through the intramolecular interactions of its dimerization domain, which spans a hundred amino-terminal residues. In the presence of both UBF dimerization domain and its immediately adjacent lysine-rich basic DNA binding domain, the E. coli expressed recombinant polypeptide, dbUBF (dimerization plus basic motifs of UBF), forms homodimers in vitro and binds to double-stranded DNA nonselectively. In gel retardation assay, dbUBF dimers make multiple shift-ladders corresponding to numerous protein dimer-DNA complexes. The UBF dimerization domain contains multiple helical structures, as predicted by EMBO-PHD program. Most of hydrophobic residues in the dimerization domain are confined in the hydrophobic phase of these hypothetic helices. Mutating these hydrophobic residues to glutamate prohibits dbUBF association and gives a different shift pattern in gel retardation assay. The results we present here argue that UBF association is largely exerted by the hydrophobic interactions between the multiple helices to bring two molecules together.

Amino Acid Sequence↗

The mitochondria are recognition organelles of cell stress.

The cellular response to stress includes synthesis of specific stress proteins in the presence of a generalized suppression of protein synthesis. The response occurs in intact animals, individually stressed organs of intact animals, donor organs upon removal, regardless of preservation methods, and cells in culture. The molecular biology of stress protein induction is not understood. While stress proteins are beneficial, overall suppression of protein synthesis, if prolonged, is harmful. Since altered energy metabolism is integral to stress induction, we examined the mitochondria to determine if they could provide a possible molecular mechanism for initiating the response. Rat myoblasts were incubated at varying temperatures for up to 120 min in [35 S] methionine. Proteins were separated electrophoretically and newly synthesized proteins visualized autoradiographically. Isolated mitochondria from resting rat myoblasts were then stressed, label incorporation determined, and newly synthesized protein was visualized. Stress sharply suppressed protein synthesis in mitochondria but autoradiograms of stressed mitochondria showed that a single stress protein of 18 kDa was synthesized. Mitochondria independently respond to stress and synthesize a stress protein from their own DNA. This protein may provide an intermediary pathway that links stressful conditions in the environment to the overall response observed in the cell.

Animals↗

Characterization of the 5'-flanking region of the gene for the alpha chain of human fibrinogen.

The 5'-flanking region of the gene coding for the alpha chain of human fibrinogen was isolated, sequenced, and characterized. The principal site of transcription initiation was determined by primer extension analysis and the RNase protection assay and shown to be at an adenine residue located 55 nucleotides upstream from the initiator methionine codon, or 13,399 nucleotides down-stream from the polyadenylation site of the gene coding for the gamma chain. Transient expression of constructs containing sequentially deleted 5'-flanking sequences of the alpha chain gene fused to the chloramphenicol acetyltransferase reporter gene showed that the promoter was liver-specific and inducible by interleukin 6 (IL-6). The shortest DNA fragment with significant promoter activity and full response to IL-6 stimulation encompassed the region from -217 to +1 base pairs (bp). Although six potential IL-6 responsive sequences homologous to the type II IL-6 responsive element were present, a single sequence of CTGGGA localized from -122 to -127 bp was shown to be a functional element in IL-6 induction. A hepatocyte nuclear factor 1 (HNF-1) binding site, present from -47 to -59 bp, in combination with other upstream elements, was essential for liver-specific expression of the gene. A functional CCAAT/enhancer binding protein site (C/EBP, -134 to -142 bp) was also identified within 217 bp from the transcription initiation site. An additional positive element (-1393 to -1133 bp) and a negative element (-1133 to -749 bp) were also found in the upstream region of the alpha-fibrinogen gene.

Amino Acid Sequence↗

Characterization of the 5'-flanking region of the gene for the gamma chain of human fibrinogen.

The 5'-flanking region of the gene coding for the gamma chain of human fibrinogen was characterized for its promoter activity. Reporter gene studies using chloramphenicol acetyltransferase as the indicator along with mutations in the DNA showed that a TATA-like sequence (-20 to -23 base pairs (bp)), a CAAT-like sequence (-54 to -57 bp), and an upstream stimulatory factor (USF) binding site (-66 to -77 bp) constitute a minimal promoter that mediates liver-specific expression of the gene. Electrophoretic gel mobility assays and antibody binding studies confirmed the interaction of USF with the binding site. An IL-6 responsive element with a sequence of CTGGAA located at -301 to -306 bp was shown to be a functional element in the IL-6 response. In contrast to the IL-6 responsive elements in the human alpha- and beta-fibrinogen genes, the element in the gene for the gamma chain of human fibrinogen was unaffected by the presence or elevated levels of the beta or delta isoforms of the CCAAT/enhancer binding proteins. A negative element with sequence homology to several silencer elements was also identified in the region of -348 to -390 bp of the gene for the gamma chain of human fibrinogen. A comparison of the regulatory elements in the genes coding for all three chains in fibrinogen is also presented.

Amino Acid Sequence↗

Searching for bone fractures: a comparison with pulmonary nodule search.

RATIONALE AND OBJECTIVES: We aimed to determine if the characteristics and principles of visual search described for the detection of pulmonary nodules apply to extremity fractures. METHODS: The eye positions of staff orthopedic radiologists, radiology residents, and medical students were monitored as they searched hand and wrist X-ray images for fractures and a chest image for nodules. RESULTS: More systematic scanning patterns were observed for experienced observers than inexperienced observers. Positive decisions for bone images were associated with prolonged gaze durations; prolonged gaze durations were significantly longer for false-negative versus true-negative decisions. Intercluster jump distances were found to be greater for chest images than bone images. CONCLUSIONS: A search for bone fractures can be qualitatively characterized by classifying observer scan paths, dwell times, and jump distances. Gaze duration can be a useful predictor of bone image locations containing potential missed fractures. Perceptual feedback could aid observers in the detection of inconspicuous fractures.

Eye Movements↗

xUBF, an RNA polymerase I transcription factor, binds crossover DNA with low sequence specificity.

Xenopus UBF (xUBF) is a transcription factor for RNA polymerase I which contains multiple DNA-binding motifs. These include a short basic region adjacent to a dimer motif plus five high-mobility-group (HMG) boxes. All of these DNA-binding motifs exhibit low sequence specificity, whether assayed singly or together. In contrast, the HMG boxes recognize DNA structure that is formed when two double helices are crossed over each other. HMG box 1, in particular, requires association of two double helices before it will bind and, either by itself or in the context of the intact protein, will loop DNA and organize it into higher-order structures. We discuss how this mode of binding affects the function of xUBF as a transcription factor.

Amino Acid Sequence↗

Caterpillar bodies: distinctive, basement membrane-containing structures in blisters of porphyria.

In a previous study, we reported on the observation of a relatively specific, linear body in the roofs of bullae from cases of porphyria cutanea tarda. In the present study, we expand on these observations to show the presence of these bodies in lesions of pseudoporphyria cutanea tarda and erythropoietic protoporphyria. Furthermore, we have applied immunoperoxidase techniques using antibodies to type IV collagen and laminin to show that they are composed of basement membrane material. Because the segmented, elongated shapes of these bodies reminded us of the larvae of butterflies, we coined the term "caterpillar bodies" to describe them. These bodies are similar in their composition to the Kamino bodies of Spitz's nevi, cylindrical bodies in adenoid cystic carcinoma, Civatte bodies of lichen planus, and the collagenous spherules seen in a number of conditions, and may provide a unique clue to the diagnosis of the porphyric bullous eruptions.

Basement Membrane↗

[Studies on the chemical constituents of Fritillaria taipaiensis L].

A new C-nor-D-homo-steroidal alkaloid named taipaienine, together with five known alkaloids namely chuanbeinone, imperialine, verticinone, perimissine and isoverticine were isolated from the bulbs of Fritillaria taipaiensis L. var. ningxiaensis Y. et W.. The unusual structure of taipaienine was a first sample with a hydroxyl group substituted at C-25 of (22)R-trans quinolizidine moiety with orientation of nitrogen lone pair. Their structures were determined by various spectral analyses.

Alkaloids↗

[Effect of electrical stimulation of hyperstriatum on nucleus dorsalis intermedius ventralis anterior thalami somatosensory units in pigeon].

Discharges of 88 somatosensory units in the nucleus dorsalis intermedius ventralis anterior thalami (DIVA) in response to afferent impulses of radial nerve on 55 urethane anesthetized pigeons were recorded and analysed. Among the 88 units, part of them also responded to the stimulation of sciatic nerve. Following electrical stimulation of somatic projecting area of hyperstriatum, the spontaneous discharges and the responses of DIVA somatosensory units to radial inputs were obviously inhibited and the degree of inhibition was linearly correlated with the frequency and intensity of stimulation. The inhibitory effect on the responses to radial inputs may cause an increase in latency and a decrease in number of spikes. These results indicate that the DIVA certainly belongs to somatosensory system, and the somatic projecting area of hyperstriatum has a descending inhibitory effect on the DIVA somatosensory units. The hyperstriatum may thus exert feedback control over its sensory inputs through descending inhibition. It appears that the functional connection between the highest region of central nervous system and thalamus in avian is similar to that of mammal.

Afferent Pathways↗

Desipramine-induced blue-gray photosensitive pigmentation.

BACKGROUND: Blue-gray pigmentation of the skin can be elicited by several medications. We report the first case (to our knowledge) of desipramine-induced photosensitive blue-gray pigmentation. OBSERVATIONS: Diffuse blue-gray pigmentation on sun-exposed surfaces was noted in a healthy 48-year-old woman who had been taking desipramine hydrochloride for 8 years. Ultrastructural studies demonstrated the presence of melanin and homogeneous electron-dense material in the dermis. CONCLUSIONS: We conclude that tricyclic antidepressant agents represent another class of medications responsible for blue-gray cutaneous pigmentation.

Desipramine↗

C-terminal truncation of bovine protein disulfide isomerase increases its activity.

Protein disulfide isomerase as usually purified by the method of Lambert and Freedman (Biochem. J., 1983, 213, 225-234) although appeared homogeneous by sodium dodecyl sulfate-polyacrylamide gel electrophoresis can be separated into two major components on a size-exclusion high performance liquid chromatography column or by polyacrylamide gel electrophoresis. These two components have the same N-terminal sequences but the C-terminal sequences are different, suggesting that one is the C-terminal slightly truncated protein. The shortened protein is more active in both the isomerase and the thiol-protein oxidoreductase activities.

Amino Acid Sequence↗

Symmetrical adenovirus minichromosomes have hairpin replication intermediates.

A special class of panhandles (hairpin or foldback structures) arising from the replication of symmetrical adenovirus (Ad) minichromosome dimers and oligomers have been identified by two-dimensional gel electrophoresis. Hairpins provide evidence for replicative intermediates in the pathway for Ad complementary-strand synthesis. Furthermore, larger inverted sequences give Ad minichromosomes a replicative advantage.

Adenoviridae↗