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Biomedical subjects

H L Su

Publications and source records attributed to H L Su.

At least 19 recordsLinked to original sources

The effect of human bcl-2 and bcl-X genes on dengue virus-induced apoptosis in cultured cells.

Infection of dengue viruses (DENs) can cause human dengue fever, hemorrhagic fever, or shock syndrome. Although DEN-induced apoptosis has been implicated in pathogenesis of the DEN-related diseases, the underlying mechanism remains largely unexplored. In this study, we investigated the effect of ectopic expression of human bcl-2 and bcl-X genes on DEN-induced apoptosis in cultured cells. We employed a human isolate of DEN serotype 2 (DEN-2), PL046, which not only caused cell-cycle arrest in the G1 phase but also induced apoptosis in infected baby hamster kidney (BHK-21) cells, murine neuroblastoma N18 cells, and human neuronal NT-2 cells. Our results reveal that overexpression of bcl-2 in fibroblast-like BHK-21 cells, although not inhibiting virus yields, delayed the process of DEN-induced apoptosis, thereby permitting surviving cells to become persistently infected. In contrast, stable bcl-2 expression in neuronal N18 cells failed to block DEN-induced apoptosis. On the other hand, Bcl-X(L), expressed predominantly in the nervous system, appeared to delay DEN's killing effect in neuronal N18 cells but not in fibroblast-like BHK-21 cells. In addition, inducible expression bcl-X(s), despite its proapoptotic property in other reported system, was found to merely accelerate cell death in DEN-infected N18 but not in infected BHK-21 cells. Thus, through studying the effect of human bcl-2-related genes, our results suggest that DEN infection may trigger target cells to undergo morphologically similar but biochemically distinct apoptotic pathways in a cell-specific manner.

Animals↗

A renal hemangiosarcoma causing hematuria in a dog.

A 14.5-year-old male dog was presented with stranguria and hematuria of 1-month duration. Hematology and blood chemistry revealed a neutrophilia, mild azotemia and a mild decrease in the packed cell volume. Urinalysis showed high specific gravity (> 1.040 g/mL), hematuria, proteinuria and mild bilirubinuria. On physical examination, a firm oval mass located caudal to the distended urinary bladder, was palpated. Differential diagnoses included prostatitis, prostatic neoplasm, prostatic hyperplasia, and abscess. The enlarged prostate was suspected to be the cause of hematuria, and a total prostatectomy was performed. Histologically, the prostate was affected by a prostatitis with cystic papillary hyperplasia of the epithelium. The dog's condition continued to deteriorate, and death occurred 1 week later. Necropsy showed a tumor mass, approximately 5 x 4 x 3 cm in size, between the abdominal aorta and the left kidney, where the adrenal glands were embedded. Lesions were found in the kidneys, adrenal gland, lungs, heart, liver, intestine, and serosa of viscera, while the spleen was spared. This hemangiosarcoma most likely arose from the renal arteries, resulting in diffuse lesions in the kidneys thought to be the cause of hematuria.

Animals↗

Direct growth suppressive activity of interferon-alpha and -gamma on human gastric cancer cells.

BACKGROUND AND OBJECTIVES: Interferons (IFNs) exhibit anti-tumor activities through either immune modulation or direct anti-tumor effects. We have investigated the activity and mechanisms of IFN-alpha and IFN-gamma on the growth of TSGH9201, TMK-1 and AGS gastric cancer cells in vitro. METHODS: Activities of IFNs on cell growth were analyzed by measuring total cellular DNA. Effects of IFNs on apoptosis was evaluated by formation of in situ DNA breakage and DNA ladders. Effects of IFNs on cells cycle phase distribution were analyzed using flow cytometry. Levels of Bcl-2 family proteins after treatment with IFNs were analyzed using Western blot. RESULTS: Both IFN-alpha and IFN-gamma were active in suppressing the growth of TSGH9201 and TMK-1 cells, while AGS cells were resistant to treatment with IFNs. The IC(50)s of IFN-alpha for TSGH9201 and TMK-1 cells were 300 and 500 U/ml, respectively, and the IC(50)s of IFN-gamma were 40 and 2.0 U/ml, respectively. Both IFN-alpha- and IFN-gamma-induced cell cycle arrest in sensitive cells. IFN-gamma also increased cellular apoptosis, demonstrated by increasing in situ DNA damage and DNA fragmentation. IFN-gamma increased BAK protein levels and decreased Bcl-2 and Bcl-X(S) protein levels in TSGH9201 cells. CONCLUSIONS: IFN-alpha suppressed growth of gastric cancer cells through induction of cell cycle arrest. IFN-gamma suppressed cell growth through induction of both cell cycle arrest and apoptosis. IFN-gamma-mediated apoptosis was associated with the alteration in protein levels of Bcl-2, Bcl-X(S) and BAK.

Antineoplastic Agents↗

Antiapoptotic but not antiviral function of human bcl-2 assists establishment of Japanese encephalitis virus persistence in cultured cells.

Upon infection of Japanese encephalitis virus (JEV), baby hamster kidney (BHK-21) and Chinese hamster ovary (CHO) cells were killed by a mechanism involved in apoptosis. While readily established in a variety of cell lines, JEV persistence has never been successfully instituted in BHK-21 and CHO cells. Since stable expression of human bcl-2 in BHK-21 cells has been shown to delay JEV-induced apoptosis, in this study we investigated whether JEV persistence could be established in such cells. When constitutively expressing bcl-2, but not its closest homolog, bcl-XL, following a primary lytic infection, approximately 5 to 10% of BHK-21 and CHO cells became persistently JEV infected during a long-term culture. From the persistent bulks, several independent clones were selected and expanded to form stable cell lines that continuously produced infectious virus without marked cytopathic effects (CPE). Among these stable cell lines, the truncated nonstructural protein 1 (NS1) was also detected and was indistinguishable from the NS1 truncations previously observed in JEV-persistent murine neuroblastoma N18 cells. However, the stable expression of NS1 alone, regardless of whether it was truncated or full length, failed to render the engineered cells persistently infected by JEV, implying that aberrant NS1 proteins were likely a consequence of, rather than a cause for, the viral persistence. Enforced bcl-2 expression, which did not affect virus replication and spread during the early phase of cytolytic infection, appeared to attain JEV persistence by restriction of virus-induced CPE. Our results suggest that it is the antiapoptotic, rather than the antiviral, effect of cellular bcl-2 which plays a role in the establishment of JEV persistence.

Amino Acid Sequence↗

[Inhibition of gastric motility by microinjection of CCK-8 into rat amygdala].

Intranulear microinjection and electrical stimulation technique were employed to evaluate the effect of ventromedial hypothalamus (VMH) on the gastric inhibition elicited by basomedial amygdala nucleus (BMA) excitation. The results were as follows: (1) Microinjections of CCk-8 (50 ng/microliter) into bilateral BAM resulted in significant decrease in intragastric pressure (IGP) and gastric motility frequency (GMF) (P < 0.01). (2) Neither CCK-A receptor antagonist [L364, 718] nor CCK-8 receptor antagonist [L365, 260] induced effects on IGP or GMF when given alone. (3) If bilateral BMA were pretreated with [L364, 718], CCK-8 could no longer induce any inhibitory effects, whlie [L365, 260] had no similar suppressive effect. (4) The inhibitory effects were not found in other nuclei in the amygdaloid body, such as bed nucleus of the stria terminalis intramygdaloid (BSTIA) and amygdaloid nucleus medial (Me). (5) Electrical stimulation of unilateral VMH or BMA would result in the inhibition of IGP and GMF. (6) After electric coagulation of VMH unilateraly injection of CCK-8 to or stimulation of homolateral VMH could no longer inhibite IGP or GMF. The above results suggest that in BMA CCK-8 exerts inhibitory effect on both motility and intragastric pressure through CCK-A receptors.

Amygdala↗

Glutaraldehyde preparations and pulpotomy in primary molars.

The study clinically and radiographically evaluated the long-term success rate of pulpotomy treatment in pulp-exposed primary molars. Five clinicians participated in this study and four glutaraldehyde preparations included 2% buffered, 2% unbuffered, 5% buffered, and 5% unbuffered glutaraldehyde solutions were used. There were 201 children, 108 boys and 93 girls, ranging in age from 4 to 7 years with 258 primary molars treated. After 36 months, 150 teeth with complete clinical records and radiographs were available for evaluation. The treatment of 98% of the patients was clinically successful, but when evaluated radiographically the overall success rate was 78.7%. The group treated with 5% buffered glutaraldehyde showed the highest success rate (87.5%) and group treated with the 5% unbuffered solution the lowest (74.1%), but no significant difference was found among the four groups. Canal obliteration was noted in 22 teeth successfully treated. Four of the teeth that were not successfully treated had canal obliteration before other pathoses became evident. The relative high failure rate in this long-term follow-up indicated that clinicians should be cautious before extensively using glutaraldehyde as a pulpotomy agent.

Chi-Square Distribution↗

Increased expression of Gi alpha 2 in mouse embryo stem cells promotes terminal differentiation to adipocytes.

The level of Gs alpha activity has been shown to modulate the rate of adipogenesis in mouse embryo fibroblast 3T3-L1 cells (H.-Y. Wang, D. C. Watkins, and C. C. Malbon. Nature Lond. 358: 334-337, 1992). For the current work the role of Gi alpha 2, a G protein mediator of inhibitory control of adenylyl cyclase, in regulating terminal differentiation of these cells was explored by stable transfection of fibroblasts expressing wild-type and a constitutively active mutant of Gi alpha 2 (Q205L). Under the influence of the cytomegalovirus promoter, the expression vector yielded a 1.7-fold (Q205L mutant Gi alpha 2) and 2.2-fold (wild-type Gi alpha 2) increase in steady-state levels of these G protein alpha-subunits. Elevation of Gi alpha 2 expression or expression of constitutively active Gi alpha 2 (Q205L) promoted lipid accumulation in these clones, the hallmark of terminal differentiation of 3T3-L1 fibroblasts to adipocytes. Increasing Gi alpha 2 activity promotes adipogenic conversion, as was previously observed by decreasing Gs alpha either by inducers of differentiation or by oligodeoxynucleotides antisense to Gs alpha. Thus Gs alpha and Gi alpha 2 are shown to be counterregulatory with respect to promoting differentiation of 3T3-L1 mouse embryo fibroblasts to adipocytes in the absence of exogenously added inducers of differentiation. This is the first report demonstrating the induction of terminal differentiation of cells by the overexpression of a G protein alpha-subunit, further implicating G proteins as regulators of complex biological responses such as adipogenesis.

3T3 Cells↗

Alteration of intracellular DNA and RNA patterns by liver arginase studied with flow cytometry.

Previous study of lymphocyte proliferation in the presence of liver arginase has indicated that arginine-depletion in the culture medium plays an important role in inhibiting cell proliferation. The inhibitory effect of both liver arginase and arginine-free condition on DNA, RNA and protein syntheses in PHA-stimulated lymphocytes were studied in cultures by measuring the incorporation of labeled precursors. Simultaneously, their influence on DNA and RNA contents in cells stained by acridine orange was investigated by automated flow cytometry. With 3 micrograms/ml arginase, the syntheses of DNA, RNA and protein were markedly inhibited after 72 h of culture. The degrees of inhibition were close to that induced in an arginine-free condition. The DNA and RNA contents of the individual cell, either cultured with 3 micrograms/ml arginase or in arginine-free medium, were arrested in G0/G1 phase. The results of cell arrest in G0/G1 phase were similar whether the cells were cultured for 24, 48 or 72 h.

Animals↗

A clinical evaluation of comprehensive dental treatment for children under general anesthesia.

The purpose of this study is to evaluate the comprehensive dental treatment for children under general anesthesia. From 1989 to 1991, 57 children with mean age of 3 years 2 months were treated, followed up with a minimal of 1 year. This procedure allows the dentition to be restored in one visit. Further care including preventive options and behavior shaping was provided on a 3-6 months recall schedule. The reasons for general anesthesia are that these children were either unable to accept treatment because of handicaps, extreme fear or young age. Their mean number of decayed tooth was 15 (Standard Deviation, SD = 5) and nearly three quarters of the children were under 6 years old. The most frequent treatment procedures were the extraction of teeth, composite resin restoration and Ni-Cr crown restoration. The Ni-Cr crown (1.7% failure rate) was more successful than the amalgam and composite resin restoration (9.7% failure rate). Pedo-strip crown had the highest failure rate (22%) for anterior teeth restoration. Nineteen children needed retreatment with conventional behavior guide. Six children had new caries and required further treatment. Thirty eight children returned for regular recall during the minimal 1 year follow-up period.

Adolescent↗

Treatment of iatrogenic Cushing's syndrome in dogs with electroacupuncture stimulation of stomach 36.

This study was conducted to evaluate the effectiveness of electroacupuncture (EA) on the recovery of adrenocortical function from Iatrogenic Cushings Syndrome (ICS) in dogs. Experiment I: Selection of the most effective Acupuncture point to treat ICS--Six healthy adult female dogs were treated bilaterally with EA for 15 minutes at loci BL22 + BL23 + BL24, ST36, or a non-locus control point on M. brachialis. Each dog was tested at all three sites in rotation. Blood samples were collected before and 0, 15 and 60 minutes after EA, and the serum cortisol levels were measured by radioimmunoassay. The data showed that EA at ST36 resulted in the highest response of serum cortisol levels among the three treatments. Experiment II: Evaluation of the effectiveness of EA ST36 in the treatment of ICS in dogs--Eight healthy adult female dogs were given prednisolone acetate 2mg/kg/day IM for 3 weeks. They were then randomly divided into ST36 and control groups of 4 dogs each. In the ST36 group, ST36 was treated bilaterally with EA for 30 minutes, 3 times per week, for 3 consecutive weeks. For the control, a non-locus point on M. brachialis was treated bilaterally with the same protocol. After the first week of EA, the serum cortisol levels of the ST36 and control groups were 0.9 +/- 0.1 and 0.5 +/- 0.1 micrograms/dl (P less than 0.005) baseline and 2.5 +/- 0.2 and 1.4 +/- 0.4 micrograms/dl (p less than 0.05) and after ACTH stimulation test, respectively. After the third week of EA treatment, the results were 1.0 +/- 0.1 and 0.6 +/- 0.2 micrograms/dl (p less than 0.05) baseline and 4.0 +/- 0.5 and 1.7 +/- 0.5 micrograms/dl (p less than 0.001) after ACTH stimulation respectively. These data indicated that EA at ST36 could restore the adrenocortical hypofunction resulting from ICS in dogs.

Acupuncture Points↗

[Influence of microinjection of bicuculline into ventrolateral medulla on the suppression of cardiac function induced by diazepam in rabbits].

Experiments were carried out on 48 rabbits anaesthetized with urethane (1 g/kg). The animals were immobilized with gallamine triethiodide and ventilated artificially. Both intravenous injection of diazepam (0.5 mg/kg) and intracerebroventricular injection of flurazepam (2 mg in 50 microliters) or gamma-aminobutyric acid (GABA) (300 micrograms in 50 microliters) decreased the peak value of left ventricular pressure area of cardiac force loop and dp/dtmax. These suppressive effects of diazepam and flurazepam were prevented by intracerebroventricular injection of picrotoxin (15 micrograms in 50 microliters) or microinjection of bicuculline (3 micrograms in 0.5 microliter) into bilateral rostral ventrolateral medulla (gamma VLM). The results suggest that the inhibitory effects of diazepam on cardiac function may be mediated by activation of GABA receptor in gamma VLM.

Animals↗

The mechanisms of inhibitory effects of liver extract on lymphocyte proliferation: II. Inhibition of DNA, RNA, and protein synthesis and their relationship to the effects of metabolic inhibitors.

The inhibitory effects of liver extract (LEx) on DNA, RNA, and protein synthesis in phytohaemagglutinin (PHA)-stimulated lymphocytes were studied by measuring the incorporation of labelled precursors. DNA, RNA, and protein synthesis were all inhibited by LEx in a dose-related manner. The inhibitory effect of LEx on protein synthesis was additive to the inhibitory effect of puromycin. The inhibitory effect of LEx on DNA synthesis was antagonistic to the inhibitory effect of mitomycin C. In the case of actinomycin D for RNA synthesis, its interactions with LEx were variable, but not additive. LEx may act as an inhibitor of protein synthesis through the mechanism of arginine-depletion.

Animals↗

Clinical versus urodynamic diagnosis in an incontinent geriatric female population.

The clinical presentation of incontinence was compared to diagnoses based on urological and urodynamic evaluation in 135 elderly women assessed consecutively in an outpatient clinic. Most patients (64 per cent) presented with mixed symptoms: 16 per cent presented with pure stress and 16 per cent with pure urge incontinence. After evaluation 46 per cent of the patients had stress incontinence with a stable bladder, 27 per cent had detrusor instability or hyperreflexia without sphincter weakness and 19 per cent had mixed urodynamic abnormalities. Presenting symptoms were predictive of urodynamic diagnosis in 64 per cent of the patients with pure stress incontinence and 55 per cent with pure urge incontinence. In general, symptoms in our patient population were less predictive of urodynamic findings than in previously reported series of younger incontinent women but they were more predictive than in other series of elderly women. Predictive values for some urodynamic findings were enhanced by combining a symptom with certain physical findings. Implications of these data for the evaluation and treatment of incontinence in the geriatric population are discussed.

Aged↗

The mechanisms of inhibitory effects of liver extract on lymphocyte proliferation. I. The extracellular mechanism of the inhibition.

Liver aqueous extract (LEx) can powerfully inhibit phytohaemagglutinin (PHA)-induced lymphocyte proliferation. The extracellular mechanism of inhibition by LEx was studied. There are three possibilities. (1) The possibility of extracellular inactivation of PHA by LEx was excluded by incubating cells with PHA first, followed by washing, and then incubating cells with LEx. The result was that LEx was still able to inhibit cell proliferation completely. (2) The possibility of competition for cell surface PHA receptors by LEx was excluded by the above experiments plus the use of N-acetyl-D-galactosamine to remove surface-bound PHA. Following this treatment, LEx was still able to inhibit cell proliferation completely. (3) The possibility of arginase-induced arginine depletion resulting in lymphocyte suppression was supported by the following experiments. Cells were incubated in media in which arginine was depleted either by reacting with LEx, and the media were afterwards bound with anti-arginase antibody, or by amino acid constituted media without arginine. The degrees of proliferation inhibition were similar in both treatments. These results indicate the important role of arginine-depletion by LEx, and may account for the LEx-induced lymphocyte inhibition.

Animals↗

Modulation of lymphocyte proliferation by murine liver extract.

Murine liver extract (LEx) purified by ammonium sulfate (45-70% saturation) possesses a strong inhibitory effect on human lymphocyte proliferation. We have shown that the inhibitory effect of LEx is not via a cytotoxic effect and that it is proportional to the length of incubation with LEx. Mitogen-prestimulated lymphocytes are more resistant to LEx inhibition than cells not prestimulated. B cells stimulated by PWM are more susceptible to LEx-induced inhibition than PHA- or Con A-stimulated T cells. In Con A cultures, there may be a population of cells more resistant to LEx inhibition. This population is not yet identified. The degree of reversibility of LEx inhibition was different in cells prestimulated by different mitogens. The inhibitory activity of LEx decreased in the presence of an increasing number of cells in the culture.

Animals↗

Genitourinary dysfunction in a geriatric outpatient population.

Clinical and urodynamic findings in 167 women and 96 men, aged 65 years and older evaluated consecutively during a four-year period in an outpatient urodynamic laboratory, are presented and compared with findings from other studies of geriatric populations. Seventy-three percent of the patients (81% of the women and 60% of the men) presented with symptoms of incontinence, most commonly of the mixed type. Although pathological lesions such as tumors and stones were rare, urodynamic abnormalities were common. Urodynamic evidence of sphincter weakness in women and detrusor motor instability were the most common urodynamic findings among patients who presented with incontinence. Close to 20% of patients who presented without incontinence also had one or more of these findings. Approximately one-third of patients had multiple urodynamic findings, emphasizing the complexity of the pathophysiology, diagnosis, and treatment of genitourinary dysfunction in many geriatric patients. Despite the long duration of symptoms in most patients, the majority were substantially improved after diagnosis and treatment of the specific genitourinary and urodynamic abnormalities detected.

Aged↗