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Biomedical subjects

H M Chung

Publications and source records attributed to H M Chung.

At least 19 recordsLinked to original sources

Antihypercholesterolemic effect of undigested fraction of soybean protein in young female volunteers.

The significant antihypercholesterolemic effect of the undigested high molecular fraction (HMF) of soybean protein is known in rats, but such an effect has not been shown in humans. The present two experiments were designed to elucidate it in humans. Subjects were female university students who had relatively high serum cholesterol levels for their age. In Experiment 1, subjects took 8% of their total energy from casein, soybean protein isolate (SPI), or HMF daily for 14 days. Five basic menus and snacks were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. The HMF group showed decreased low-density lipoprotein cholesterol (LDL-C) as compared to other groups. In Experiment 2, subjects took 4% of total energy from casein or HMF daily for a menstruation period. Five basic menus and snacks which contained two egg yolks (about 500 mg cholesterol) were cycled. Energy intakes and daily activities were kept constant and body weight was maintained. A decrease in LDL-C and an increase in high-density lipoprotein cholesterol (HDL-C) were observed in the HMF group as compared to the casein group. Fecal acidic steroid excretion was greater in the HMF group than in the casein group (p < 0.05). The results confirmed that HMF increases fecal steroid excretion and reduces serum cholesterol levels in humans.

Adult

The location of the third cleavage plane of Xenopus embryos partitions morphogenetic information in animal quartets.

Analysis of the developmental potential of animal quartets (the set of four animal blastomeres isolated from the 8-cell stage Xenopus embryo) provided insight into the manner in which morphogenetic information is distributed along the animal-vegetal axis. Gravity treatments were employed to alter the partitioning plane. Animal quartets isolated from embryos exposed to simulated weightlessness had larger animal blastomeres, and they formed structures such as a groove and a protrusion more often than 1g-control animal quartets. Animal quartets with an unusual non-horizontal third cleavage plane were also found to have a higher frequency of protrusion formation than animal quartets with a typical horizontal cleavage plane. The increase in the frequency seen in simulated weightlessness animal quartets was not due to their increased size. Fusing two animal quartets isolated from hypergravity (3g) exposed embryos (small blastomeres and low incidence of protrusions) did not affect the frequency of protrusion formation. Molecular analyses revealed that a partial induction was associated with the protrusion formation. Transcripts of the dorsal lip specific homeobox gene, goosecoid, and alpha-cardiac actin were detectable by PCR amplification in the animal quartet with a protrusion, and alpha-cardiac actin mRNA was found by whole-mount in situ hybridization to be localized in the protrusion. Taken together, all these results are consistent with the notion that both animal and vegetal information is necessary for normal development and the partitioning of morphogenetic information into animal quartets results in gravity-dependent differential morphogenesis and gene regulation.

Actins

Early amphibian (anuran) morphogenesis is sensitive to novel gravitational fields.

Anuran amphibian embryos (Xenopus laevis and Rana dybowskii) are sensitive to novel gravitational fields. Under simulated weightlessness, (i) the location of the first horizontal cleavage furrow was shifted toward the vegetal pole at the eight-cell stage; (ii) the position of the blastocoel was more centered, and the number of cell layers in the blastocoel roof was increased at the blastula stage; (iii) the dorsal lip appeared closer to the vegetal pole at the gastrula stage; and (iv) head and eye dimensions were enlarged at the hatching tadpole stage. Effects of simulated hypergravity were opposite to those of simulated weightlessness, except that hypergravity, unlike simulated weightlessness, reduced the number of primordial germ cells in feeding tadpoles. Despite those dramatic differences in the early embryogenesis, tadpoles at the feeding stage are largely indistinguishable from controls.

Animals

Disruption of largest subunit RNA polymerase II genes in Trypanosoma brucei.

Two types of largest subunit RNA polymerase II (pol II) genes (pol IIA and pol IIB), differing in 3 amino acid substitutions, are encoded in the Trypanosoma brucei (stock 427-60) genome. As a result, the alpha-amanitin-resistant transcription of the procyclic acidic repetitive protein (PARP) and variant surface glycoprotein (VSG) genes was proposed to involve a modified, alpha-amanitin-resistant form of the largest subunit of pol II. Alternatively, pol I could transcribe the PARP and VSG genes. To discriminate between these two models, we deleted the N-terminal domain (about one-third of the polypeptide), which encodes the amino acid substitutions which discriminated the pol IIA and pol IIB genes, at both pol IIB alleles. The pol IIB- trypanosomes still transcribe the PARP genes and the VSG gene promoter region in insect-form trypanosomes by alpha-amanitin-resistant RNA polymerases, while control housekeeping genes are transcribed in an alpha-amanitin-sensitive manner, presumably by pol IIA. We conclude that the alpha-amanitin-resistant transcription of protein coding genes in T. brucei is not mediated by a diverged form of the largest subunit of pol II and that the presence of both the pol IIA and pol IIB genes is not essential for trypanosome viability. This conclusion was further supported by the finding that individual trypanosome variants exhibited allelic heterogeneity for the previously identified amino acid substitutions and that various permutations of the polymorphic amino acids generate at least four different types of largest subunit pol II genes. The expression of the PARP genes and the VSG gene promoter region by alpha-amanitin-resistant RNA polymerases in the pol IIB- trypanosomes provides evidence for transcription of these genes by pol I.

Amanitins

Discovery and characterization of a new transposable element, Tn4811, in Streptomyces lividans 66.

Transposition of a new 5.4-kb transposon, Tn4811, of Streptomyces lividans to the melC operon of Streptomyces antibioticus on plasmid pIJ702 was discovered. The nucleotide sequence of this copy of Tn4811, which contained an imperfect (9 of 11 bp) terminal inverted repeat, five putative Streptomyces coding sequences for an oxidoreductase and its transcription regulator, and three transposition-related proteins, was determined. SLP- strains of S. lividans contained one copy (A) of Tn4811, while SLP2+ strains contained an additional copy (B) on the SLP2 plasmid. The nucleotide sequences at three insertion junctions of Tn4811 were determined. Copy B lacked 41 bp from the left end. At the other five junctions the duplication of a putative 3-bp target sequence (TGA) was observed. A sequence of less than 3 kb homologous to Tn4811 was present in S. antibioticus. DNA homologous to Tn4811 was not detected in 14 other Streptomyces species.

Amino Acid Sequence

RNA polymerase I can mediate expression of CAT and neo protein-coding genes in Trypanosoma brucei.

We show that the ribosomal RNA (rRNA) promoter can efficiently direct expression of protein-coding genes in the parasitic protozoan Trypanosoma brucei. The rRNA promoter was characterized by: (i) point mutations at the rRNA transcription initiation site which completely abolished its promoter function in transient CAT transformation assays; (ii) the alpha-amanitin resistance of transcription of rRNA promoter-neomycin phosphotransferase (neo) genes in stably transformed trypanosomes; and (iii) the nucleolar location of neo RNA, synthesized under the control of the rRNA promoter. The rRNA promoter-derived CAT mRNA required a 3' splice acceptor site and the neo mRNA was trans-spliced and polyadenylated. In situ hybridization revealed neo RNA at the nucleolus in stably transformed trypanosomes in which rRNA promoter-neo constructs were integrated either at a rRNA locus or at a locus for the procyclic acidic repetitive protein (PARP) coding genes. We postulate that trans-splicing, by uncoupling the requirement for transcription of protein-coding genes by RNA polymerase II, allows RNA polymerase I mediated protein-coding gene transcription, presumably because a 5' cap can be transferred to the pre-mRNA by trans-splicing.

Amanitins

Characterization of VSG gene expression site promoters and promoter-associated DNA rearrangement events.

The expressed variant cell surface glycoprotein (VSG) gene of Trypanosoma brucei is located at the 3' end of a large, telomeric, polycistronic transcription unit or expression site. We show that the region 45 kb upstream of the VSG gene, in the expression site on a 1.5-Mb chromosome, contains at least two promoters that are arranged in tandem, directing the transcription of the expression site. DNA rearrangement events occur specifically, at inactivation of the expression site, and these events delete the most upstream transcribed region and replace it with a large array of simple-sequence DNA, leaving the downstream promoter intact. Because of the placement of simple-sequence DNA, the remaining downstream promoter now becomes structurally identical to previously described VSG promoters. The downstream promoter is repetitive in the genome, since it is present at several different expression sites. Restriction fragment length polymorphism mapping allows grouping of the expression sites into two families, those with and those without an upstream transcription unit, and the DNA rearrangement events convert the expression sites from one type to the other. Deletion of the upstream transcription unit also leads to the loss of several steady-state RNAs. The findings may indicate a role for promoter-associated DNA rearrangement events, and/or interactions between tandemly arranged promoters, in expression site transcriptional control.

Animals

Hypertension as an unusual feature in an outbreak of tetrodotoxin poisoning.

We report an outbreak of tetrodotoxin poisoning resulting from consumption of ovaries of an unidentified species of fish. Thirty victims manifested the typical neurologic symptoms of tetrodotoxin poisoning. Although hypotension is the classically described blood pressure reaction, eight individuals developed hypertension (average blood pressure 192/110 mm Hg); one died of acute pulmonary edema. Semi-quantitative tetrodotoxin bioassay of two uneaten ovaries revealed tetrodotoxin concentrations of 54 Mouse Units/gm and 287 Mouse Units/gm, respectively. To gain insight into the unusual phenomenon of hypertension observed in our outbreak, we interviewed the victims, performed a funduscopic exam for hypertensive retinopathy and checked their blood pressure periodically in the ensuing year. Mild hypertension evidenced by retinopathy and elevated blood pressure was found in all seven who manifested hypertension during the acute event and survived. We postulate that individuals with pre-existing hypertension responded to the relatively small doses of tetrodotoxin with a dramatic rise in blood pressure. This resulted in the fatal outcome for one individual with severe coronary artery disease. Hypertension should be recognized as a possible feature of tetrodotoxin poisoning, especially in predisposed individuals.

Adult

Taiwan National Poison Center survey of glyphosate--surfactant herbicide ingestions.

Between January, 1986 and September, 1988, the Taiwan National Poison Center recorded 97 telephone consultations (49 male, 48 female) on cases of ingestion of glyphosate-surfactant herbicide concentrate containing the isopropylamine salt of glyphosate (N-phosphonomethyl glycine, CAS 1071-83-6) and a non-ionic tallow amine surfactant. Eleven of the cases resulted in fatalities, all among those attempting suicide. The average amount ingested by survivors was 120 +/- 112 mL and by nonsurvivors was 263 +/- 100 mL (p less than or equal to 0.0001). The average age of survivors was 35 +/- 15 years compared to 54 +/- 11 years for fatalities (p less than or equal to 0.0002). Irritation of the oral mucous membrane and gastrointestinal tract was the most frequently reported effect. Other effects recorded were pulmonary dysfunction, oliguria, metabolic acidosis, hypotension, leukocytosis and fever. Fourteen patients received either atropine or pralidoxime plus atropine despite the fact that glyphosate does not inhibit acetylcholinesterase. Thirteen percent of patients received a urine test for paraquat or treatment customarily used for paraquat ingestion, possibly reflecting similar initial presentations following ingestion of these two herbicides. Laboratory differentiation is essential if any doubt exists about which herbicide was ingested. Patients ingesting large volumes of concentrated glyphosate-surfactant herbicide formulations require close observation and supportive treatment.

Accidents

Architectural organization in the interphase nucleus of the protozoan Trypanosoma brucei: location of telomeres and mini-chromosomes.

We studied the spatial organization of chromatin in the interphase G1, S and G2 nucleus of the protozoan Trypanosoma brucei, applying in situ hybridization with conventional fluorescence and confocal scanning optical microscopy. The majority of the trypanosome telomere GGGTTA repeats from different chromosomes were found clustered together, either extending in a network through the nuclear interior or localized at the nuclear periphery. The population of one hundred mini-chromosomes was often asymmetrically located: either clustered in a narrow band in close association with the nuclear envelope or distributed into several clusters that segregated into roughly one half of the nucleus. The nuclear organization may undergo modifications during the cell cycle and development. We conclude that non-random spatial positioning of DNA exists in the nucleus of this protozoan. Finding a high level of structural organization in the interphase nucleus of T.brucei is an important first step towards understanding chromosome structure and functioning and its role in the control of gene expression.

Animals

Reduction of serum calcium by sodium sulfonated polystyrene resin.

Sodium resin has been clinically administered against hyperkalemia widely, but its effects of lowering the serum calcium has never been documented. In our study, 7 patients with chronic renal failure were chosen at random to take sodium resin 30 g per day for 3 days. The sodium resin not only lowered the serum potassium level (p less than 0.05) but also brought down the level of serum calcium (p less than 0.05). The reduced ability of patients with chronic renal failure to absorb calcium from the gastrointestinal tract is well recognized, so its effects of lowering calcium will be more likely to aggravate the serum calcium imbalance further. If sodium resin has to be used for the maintainance of serum potassium in patients with chronic renal failure the serum calcium should be monitored closely in order to lighten the osteodystrophy and secondary hyperparathyroidism.

Adult

[Protease activities in gastric and colon cancer tissues].

Activities of cathepsin B, cathepsin L, and plasminogen activators (urinary type plasminogen activator and tissue type plasminogen activator) were assayed in homogenates of cancer tissue, normal tissue closely surrounding the cancer tissue, and normal tissue distant from the cancer tissue from 30 patients undergoing surgery for gastric cancers and 10 patients undergoing surgery for colon cancers. Activities of those proteases were also assayed in homogenates of adenoma tissue from 10 patients undergoing polypectomy for colon polyps. In the gastric cancer tissue homogenates, the activities of cathepsin B, cathepsin L and tissue type plasminogen activator were significantly higher than in normal tissues. By contrast, the activities of urinary type plasminogen activator of gastric cancer tissues were significantly lower than normal tissues. In the colon cancer tissue homogenates, the activities of cathepsin, B, cathepsin L, and urinary type plasminogen activator were significantly higher than in normal tissues. On the other hand, the activities of tissue type plasminogen activator of cancer tissues were significantly lower than normal tissues. But there were no significant differences in the activities of plasminogen activators between the cancer tissues and adenoma tissues. These results suggest that cathepsin B and cathepsin L play an important role in gastric and colon cancer proliferation and evolution, although the roles of plasminogen activators in gastric and colon cancer proliferation and evolution and in the colon adenoma-carcinoma sequence are still unknown.

Cathepsin B

Autonomous death of amphibian (Xenopus laevis) cranial myotomes.

The death of cranial myotomes during Xenopus laevis embryogenesis is employed as a model system to study programmed cell death. The first primary myotomes to differentiate and functionally develop are in the occipital region of the embryonic head. Between stages 27 (tailbud) and 48 (feeding tadpole), they degenerate and disappear in a craniocaudal sequence. Descriptive and experimental studies were undertaken to establish whether this apparent cell (myotome) death program is autonomous or whether it depends on interactions with surrounding tissues (e.g., otic vesicle). Removal of the adjacent otic vesicle did not affect cranial myotome death. Likewise, grafting the otic vesicle to a novel location along the somite file did not induce local myotome degeneration (death). Cranial myotome primordia grafted into the trunk region degenerated on schedule. Trunk myotome primordia grafted to the cranial myotome location did not degenerate. It is therefore concluded that the cranial myotome death program has become autonomous by the time the cranial myotomes reach the developmental stage of segmentation.

Animals

Amphibian (urodele) myotomes display transitory anterior/posterior and medial/lateral differentiation patterns.

Myotome differentiation during Mexican axolotl (Ambystoma mexicanum) somitogenesis was analyzed by employing anti-actin and anti-myosin monoclonal antibodies as molecular probes. Myotome differentiation occurs after segmentation and proceeds in the cranial-to-caudal direction along the somite file. Within individual somites myotome differentiation displays distinct polarities. Examination of the somite file at the tailbud stage revealed that soon after segmentation, actin/myosin accumulate predominantly in the anterior and medial region of the myotome initially. Subsequently, cells within the myotome differentiate in an anterior-to-posterior and medial-to-lateral direction. Experimental analysis of presomitic paraxial mesoderm grafts before segmentation revealed that this transient myotome polarity is autonomous. Comparative analyses indicate that this myotome differentiation pattern is urodele specific. Cynops pyrrhogaster undergoes myotome differentiation like the axolotl, while two anurans, Xenopus laevis and Bombina orientalis, do not.

Actins

First identification of acute tetrodotoxin-associated food poisoning in Taiwan.

Attempt was made to elucidate the responsible toxin in fish which recently caused food poisoning in Ilan County, Taiwan. The causative fish was assayed for anatomical distribution of toxicity (as tetrodotoxin). The roe showed the highest toxicity (1200 mouse units per gram, abbreviated as MU/g), followed by the dermis (150 MU/g) and muscle (120 MU/g). The toxins were partially purified from the methanolic extracts of the fish muscle and roe by ultrafiltration and Bio-Gel P-2 column chromatography. Thin-layer chromatography, cellulose acetate membrane electrophoresis and high performance liquid chromatography analysis demonstrated that the toxins consisted of tetrodotoxin and anhydrotetrodotoxin. It was concluded that the causative agent of the above food poisoning was tetrodotoxin.

Animals

Clinical assessment of extracellular fluid volume in hyponatremia.

Assessment of the status of extracellular fluid volume is important in evaluating the cause and selecting appropriate therapy for hyponatremic disorders. Since the sensitivity and specificity of clinical assessment of extracellular fluid volume status in hyponatremic states remain unknown, 58 non-edematous patients with serum sodium less than 130 meq/liter were prospectively evaluated. Patients were judged to be either normovolemic (no response of serum sodium to saline infusion) or hypovolemic (saline infusion significantly corrected hyponatremia). Hypovolemic patients had significantly higher plasma renin activity (5.0 +/- 1.5 versus 2.5 +/- 0.5 ng/ml per three hours, p less than 0.05) and norepinephrine (1,054 +/- 252 versus 519 +/- 55 pg/ml, p less than 0.05) concentrations than did normovolemic patients. Clinical assessment correctly identified only 47 percent of hypovolemic patients and 48 percent of normovolemic patients. Thus, clinical assessment was of limited sensitivity and specificity in identifying extracellular fluid volume status in these hyponatremic patients. However, the concentration of sodium in a spot urine sample clearly separated hypovolemic (mean UNa = 18.4 +/- 3.1 meq/liter) from normovolemic (mean UNa = 72 +/- 3.7 meq/liter, p less than 0.001) hyponatremic patients.

Extracellular Space

Beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease: effect of propranolol.

This study was designed to investigate beta-adrenergic-mediated extrarenal potassium disposal in patients with end-stage renal disease (ESRD). Plasma potassium was measured over a period of 3 months in 20 patients with ESRD who were receiving the nonselective beta-blocker propranolol (n = 10) or not (n = 10). Both groups were virtually anuric and had a comparable plasma BUN, plasma bicarbonate, and red cell Na-K-ATPase activity. Plasma potassium measured before dialysis was higher in propranolol users than in nonusers (5.6 +/- 0.2 and 4.6 +/- 0.1 mEq/l, p less than 0.005). To examine beta-adrenergic-mediated internal potassium disposal more directly, epinephrine and epinephrine plus propranolol were acutely administered to another group of patients with ESRD and to normal subjects. Epinephrine resulted in a similar fall in plasma potassium in both groups (0.69 +/- 0.20 and 0.63 +/- 0.07 mEq/l, respectively), thereby suggesting unimpaired beta-adrenergic-mediated extrarenal potassium handling in patients with ESRD. In patients, however, the response to epinephrine was heterogeneous. In 4 of the 10 patients studied, epinephrine infusion did not result in a decrement in plasma potassium suggesting impaired beta-adrenergic responsiveness and thus blunting of this mechanism of extrarenal potassium disposal. In the remaining 6 patients, epinephrine infusion resulted in a fall in plasma potassium which was greater than that observed in normal subjects (1.13 +/- 0.14 and 0.63 +/- 0.07 mEq/l, respectively, p less than 0.01). In the presence of propranolol, the infusion of epinephrine did not result in a decrement in plasma potassium in these 6 patients or in the 6 normal subjects (0.04 +/- 0.07 and -0.02 +/- 0.06 mEq/l, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists

Postoperative hyponatremia. A prospective study.

In the present study, we found that at least 4.4% of 1,088 prospectively studied patients developed postoperative hyponatremia (plasma sodium concentration less than 130 mEq/L). Most patients (42%) were normovolemic. Edematous states (21%), hyperglycemia (21%), volume depletion (8%), and renal failure (8%), however, were also common settings of postoperative hyponatremia. Plasma arginine vasopressin was present in all patients in whom it was measured and 94% of the patients were receiving hypotonic fluid at the time of development of hyponatremia. Hyponatremia was not associated with significant neurologic deterioration in the 48 postoperative patients in the present study. In eight patients, however, the positive water balance that resulted in hyponatremia was associated with development of pulmonary vascular congestion. We conclude that hyponatremia commonly occurs following all types of surgical procedures and is due to hypotonic fluid administration in the presence of nonosmotic secretion of arginine vasopressin.

Adult