Biomedical subjects

B S Lee

Publications and source records attributed to B S Lee.

At least 19 recordsLinked to original sources

PubMed1996

Roles of protein phosphatase 1 and 2A in an IL-6-mediated autocrine growth loop of human myeloma cells.

Deregulation of IL-6 production is one of the major causes for human multiple myeloma. Exogenous IL-6 stimulated the proliferation of fresh human myeloma cells and the myeloma cell line, U266, which produced IL-6 spontaneously. Anti-IL-6 antibody and IL-6 antisense oligonucleotide suppressed the IL-6 stimulated myeloma cell proliferation, indicating that IL-6 induced the myeloma cell proliferation via an autocrine loop. Okadaic acid, an inhibitor of protein phosphatase 1 and 2A, inhibited the U266 cell proliferation at a concentration of less than 1 ng/ml. At this concentration, okadaic acid suppressed the IL-6-induced IL-6 gene expression of myeloma cells. It seems that the okadaic acid blocked the myeloma cell proliferation by reducing IL-6 synthesis in myeloma cells. In addition, IL-6 itself also regulated IL-6 receptor expression. Analysis by FACScan and RT-PCR showed that anti-IL-6 antibody treatment up-regulated IL-6 receptor expression. Interestingly, the presence of okadaic acid induced the up-regulation of IL-6 receptor expression as well as the down-regulation of IL-6-induced gp130 phosphorylation in the myeloma cells. Taken together, these data suggest that protein phosphatase 1 and 2A are involved in IL-6-mediated autocrine growth of human myeloma cells by modulating IL-6 signaling and IL-6 receptor expression in myeloma cells.

Animals↗

PubMed1995

High-pressure proton NMR study of lateral self-diffusion of phosphatidylcholines in sonicated unilamellar vesicles.

Effects of pressure on the lateral diffusion of phospholipid molecules in sonicated pure 1,2-dipalmitoylphosphatidylcholine (DPPC) and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) vesicles (15 wt%) in D2O were examined using the high-pressure proton NMR rotating frame spin-lattice relaxation time (T1rho) method. Proton T1rho were measured at pressures from 1 bar to 5000 bar and at temperatures of 50 degrees C to 70 degrees C for DPPC and 5 degrees C to 35 degrees C for POPC. The T(-1)1rho values were plotted as a function of the square root of the spin-locking field angular frequency (omega1(1/2) and the lateral diffusion coefficient (D) calculated from the slope. Pressure effects on lateral diffusion were observed in the liquid-crystalline (LC) phase. The lateral diffusion coefficient exhibited sharp decreases in response to the various pressure-induced phase transitions encountered. However, pressure had little, if any, effect on lateral diffusion in the pressure-induced gel I (GI) phase and pressure-induced interdigitated gel (Gi) phase. The activation volumes for diffusion were calculated from the slopes from plots of In D versus pressure for both DPPC (37 ml/mol at 50 degrees C, 34 ml/mol at 60 degrees C and 25 ml/mol at 70 degrees C) and POPC (16 ml/mol at 5 degrees C, 9 ml/mol at 20 degrees C and 6 ml/mol at 35 degrees C) sonicated vesicles in the LC phase. The activation energy for diffusion (Ea) was calculated using the slopes from plots of In D versus the inverse of the temperature (1/T) for both DPPC and POPC in the LC phase (3.5 kcal/mol and 3.9 kcal/mol, respectively) and for both DPPC and POPC in the GI phase (6.0 kcal/mol and 4.4 kcal/mol, respectively). From the lateral diffusion coefficient and line width data pressure-temperature phase diagrams for sonicated pure DPPC and POPC vesicles were constructed. The values of the temperature to pressure equivalence of DPPC (dTm/dP) were estimated to be 22.1 degrees C/kbar for the LC to GI phase transition and 28.6 degrees C/kbar for the GI to Gi phase transition. The value of the temperature to pressure equivalence of POPC for the LC to GI phase transition was estimated to be 19.0 degrees C/kbar.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed1995

Identification of an additional gene required for eukaryotic nonsense mRNA turnover.

Loss of function of any one of three UPF genes prevents the accelerated decay of nonsense mRNAs in Saccharomyces cerevisiae. We report the identification and DNA sequence of UPF3, which is present in one nonessential copy on chromosome VII. Upf3 contains three putative nuclear localization signal sequences, suggesting that it may be located in a different compartment than the cytoplasmic Upf1 protein. Epitope-tagged Upf3 (FLAG-Upf3) does not cofractionate with polyribosomes or 80S ribosomal particles. Double disruptions of UPF1 and UPF3 affect nonsense mRNA decay in a manner indistinguishable from single disruptions. These results suggest that the Upf proteins perform related functions in a common pathway.

Amino Acid Sequence↗

PubMed1995

Gene RPA43 in Saccharomyces cerevisiae encodes an essential subunit of RNA polymerase I.

Yeast RNA polymerase I contains 14 distinct polypeptides, including A43, a component of about 43 kDa. The corresponding gene, RPA43, encodes a 326-amino acid polypeptide matching the peptidic sequence of two tryptic fragments isolated from A43. Gene inactivation leads to a lethal phenotype that is rescued by a plasmid containing the 35S ribosomal RNA gene fused to the GAL7 promoter, which allows the synthesis of 35S rRNA by RNA polymerase II in the presence of galactose. A screening for mutants rescued by the presence of GAL7-35SrDNA identified a nonsense rpa43 allele truncating the protein at amino acid position 217. [3H]Uridine pulse labeling showed that this mutation abolishes 35S rRNA synthesis without significant effects on the synthesis of 5 S RNA and tRNAs. These properties establish that A43 is an essential component of RNA polymerase I. This highly hydrophilic phosphoprotein has a strongly acidic carboxyl-terminal domain, and shows no homology to entries in current sequence data banks, including all the genetically identified components of the other two yeast RNA polymerases. RPA43 mapped next to RPA190, encoding the largest subunit of polymerase I. These genes are divergently transcribed and may thus share upstream regulatory elements ensuring their co-regulation.

Amino Acid Sequence↗

PubMed1995

Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage.

The activation of heat shock genes by diverse forms of environmental and physiological stress has been implicated in a number of human diseases, including ischemic damage, reperfusion injury, infection, neurodegeneration, and inflammation. The enhanced levels of heat shock proteins and molecular chaperones have broad cytoprotective effects against acute lethal exposures to stress. Here, we show that the potent antiinflammatory drug indomethacin activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1). Perhaps relevant to its pharmacological use, indomethacin pretreatment lowers the temperature threshold of HSF1 activation, such that a complete heat shock response can be attained at temperatures that are by themselves insufficient. The synergistic effect of indomethacin and elevated temperature is biologically relevant and results in the protection of cells against exposure to cytotoxic conditions.

DNA-Binding Proteins↗

PubMed1995

Transcriptional regulation of the vacuolar H(+)-ATPase B2 subunit gene in differentiating THP-1 cells.

Monocyte-macrophage differentiation was used as a model system for studying gene regulation of the human vacuolar H(+)-ATPase (V-ATPase). We examined mRNA levels of various V-ATPase subunits during differentiation of both native monocytes and the cell line THP-1, and found that transcriptional and post-transcriptional mechanisms could account for increases in cell V-ATPase content. From nuclear runoff experiments, we found that one subunit in particular, the B2 isoform (Mr = 56,000), was amplified primarily by transcriptional means. We have begun to examine the structure of the B2 subunit promoter region. Isolation and sequencing of the first exon and 5'-flanking region of this gene reveal a TATA-less promoter with a high G + C content. Primer extension and ribonuclease protection analyses indicate a single major transcriptional start site. We transfected promoter-luciferase reporter plasmids into THP-1 cells to define sequences that mediate transcriptional control during monocyte differentiation. We found that sequences downstream from the transcriptional start site were sufficient to confer increased expression during THP-1 differentiation. DNase I footprinting and sequence analysis revealed the existence of multiple AP2 and Sp1 binding sites in the 5'-untranslated and proximal coding regions.

Base Sequence↗

PubMed1995

Effect of qigong training on proportions of T lymphocyte subsets in human peripheral blood.

The effect of Qigong training on proportions of T lymphocyte subsets was investigated in human peripheral blood. We observed that the ratio of CD4+/CD8+ T lymphocytes was increased as much as 50% in a trainee group who practiced Qigong training more than 5 months compared to a normal healthy group who did not practice. The absolute number of CD4+ T lymphocytes was also elevated in trainee group with 100 cells/mm3 more than in normal healthy group. The positive correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD4+45RA-/CD4+CD45RA+ T lymphocytes was shown in the trainee group. In contrast, there was a negative correlation between the ratio of CD4+/CD8+ T lymphocytes and the ratio of CD8+CD57+/CD8+CD57- T lymphocytes in the trainee group. The data indicate that Qigong training affects the profile of lymphocyte subsets in human peripheral blood, especially the proportion of CD4+ T lymphocytes.

Adult↗

PubMed1994

Synergistic cooperation between phorbol ester and IFN-gamma for induction of nitric oxide synthesis in murine peritoneal macrophages.

The role of protein kinase C (PKC) in the induction of nitric oxide (NO) synthesis in murine peritoneal macrophages was examined. Phorbol ester, a PKC activator, had no effect on NO synthesis by itself, whereas IFN-gamma alone had modest activity. When phorbol ester was used in combination with IFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. This increase in NO synthesis was reflected as increased amount of inducible NO synthase (iNOS) mRNA, as determined by Northern blotting. The optimal effect of phorbol ester was shown at 6 h after treatment with IFN-gamma. Phorbol ester also induced the release of NO to the incubation medium by bacillus Calmette-Guerin-infected peritoneal macrophages. Prolonged incubation of cells with phorbol ester, which down-regulates PKC activity, abolished the synergistic cooperative effect on NO production with IFN-gamma. In addition, such PKC inhibitors as staurosporin or polymyxin B reduced NO production induced by IFN-gamma plus phorbol ester. When the cells were treated with both actinomycin D and phorbol ester after IFN-gamma stimulation, more NO was produced and more iNOS mRNA was expressed than in the cells treated with actinomycin D alone. On the basis of these observations, we conclude that PKC might not be directly involved in the expression of NO synthase, but, instead, might be involved in the stabilization of the iNOS mRNA already expressed by the treatment of IFN-gamma.

Alkaloids↗

PubMed1994

Reversal of diastolic cerebral blood flow in infants without brain death.

The reversal of diastolic cerebral blood flow has been regarded as a characteristic waveform of brain death and a useful confirming sign. We report 2 patients who had diastolic flow reversal but survived. One, a 1-month-old boy with status epilepticus, had reversal of diastolic cerebral blood flow detected by Doppler ultrasound soon after admission. Reversal disappeared after medical management for increased intracranial pressure and seizure control. He recovered without sequelae. The other, a 6-month-old girl with choroid plexus papilloma, had reversal of diastolic flow during abrupt clinical deterioration. Emergent surgical removal of the tumor was performed and she survived with hemiparesis and psychomotor retardation. Our patients demonstrated that even in the presence of diastolic reversal of cerebral blood flow, prompt and effective treatment can avoid a fatal outcome.

Blood Flow Velocity↗

PubMed1994

Pulsatile gonadotrophin-releasing hormone therapy in patients with pituitary tumours treated by surgery and irradiation.

OBJECTIVE: Pulsatile administration of GnRH for induction of ovulation is effective for women with idiopathic hypogonadotrophic hypogonadism. We were interested to assess the pituitary-ovarian response to pulsatile GnRH infusion and the therapeutic effectiveness of restoring ovulation in a group of hypogonadotrophic women previously treated with surgery and irradiation to pituitary tumours. PATIENTS: The group of patients comprised 15 hypogonadotrophic women, aged 29-40 years (mean 32.4 years), who had undergone transsphenoidal adenomectomy or craniotomy and irradiation with a total of 4500-5400 cGy in 25 fractional doses divided over 5-6 weeks. The time interval from irradiation to study was 6.3 +/- 2.0 years (mean +/- SD). TREATMENT: A single bolus GnRH (100 micrograms) test and pulsatile infusion of GnRH were performed to assess the pituitary gonadotrophin reserve and induce ovulation. We tried to correlate the pituitary response with characteristics of intracranial lesions on computerized tomography findings. We undertook ovarian biopsy in one patient who failed to respond to gonadotrophin therapy and pulsatile infusion of GnRH. RESULTS: Twelve women (80%) showed evidence of ovulation in response to pulsatile GnRH treatment and five subsequently became pregnant. Four of 12 ovulators were previous non-ovulators to exogenous gonadotrophin therapy. There was no correlation between pituitary response and character of lesions based on computerized tomography findings. A patient who failed to respond to either gonadotrophin or pulsatile infusion of GnRH had premature ovarian failure on ovarian histology. CONCLUSIONS: The functional reserve capacity of pituitary gonadotrophs may remain less impaired by tumour encroachment, pituitary surgery or irradiation than had previously been thought. This holds promise for ovulation induction in hypogonadotrophic patients who had been treated with surgery and irradiation for pituitary tumours.

Adult↗

PubMed1994

Acute herpetic esophagitis--a case report.

We report a case of acute herpetic esophagitis in a 33 year old man who was presumed to be immuno-compromised following prolonged steroid and cyclosporin treatment for acute rejection of a transplanted kidney. In Korea, all reported cases of herpetic esophagitis have been diagnosed in immuno-compromised and debilitated patients with a typical endoscopic appearance of ulcerating lesions. However, our patient showed multiple vesicular lesions without ulcer along the entire esophagus. The diagnosis was confirmed by colorimetric detection of herpes virus DNA using in situ hybridization. The endoscopic findings reported herein probably represent the typical early stage of acute herpetic esophagitis.

Acute Disease↗

PubMed1994

[Analysis of tuberculosis cases among students reported from Osaka prefectural high schools and counter--measures for tuberculosis].

The number of newly registered cases of tuberculosis has been increasing in the age group 15-19 year-old and over. To investigate the prevention of tuberculosis among young people under 20 years old, a survey was conducted on reported cases of tuberculosis among Osaka Prefectural high school students during the period from April, 1989 to May, 1994. Altogether 67 cases were reported from their schools during this period. Although there was a decrease in the total number of students since 1990, there was no corresponding decrease in the number of cases of tuberculosis. Of the total number of cases among high school students registered at public health centers in Osaka, only 23% were reported from the high schools. Cases confirmed bacteriologically positive consisted 13% of all cases. Male students accounted for 61% of reported cases. The methods of detection included medical consultation due to symptoms (75%), mass radiography (18%) and pre-employment health checkup (7%). 46% of cases reported during the first school year were discovered by mass radiography. While 24% of all cases were detected in April, no less than 46% of cases among those in the first school year were detected in April. Compared with those detected in any other school years, cases detected in the first school year showed some characteristic differences with regards to detection and bacteriological results. There has been one tuberculosis epidemic which accounted for six cases during the past five years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Generation of nitric oxide inhibits formation of superoxide in macrophages during activation.

We have studied the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages during activation. The production of NO was induced by activation of cells with recombinant interferon-gamma (rIFN-gamma) and lipopolysaccharide (LPS). Phorbol 12-myristate 13-acetate (PMA)-induced formation of superoxide also increased during activation. However, NO released by the activated macrophages exerted the inhibitory effect on the superoxide formation in the same cells. This fact is supported by the increased production of superoxide when the cells were treated with NG-monomethyl-L-arginine (NGMMA) in addition to stimulation with rIFN-gamma and LPS. The production of superoxide was also inhibited by treatment with sodium nitroprusside (SPN), which spontaneously released nitric oxide in vitro, and at the same time there was increased adenosine diphosphate (ADP)-ribosylation of 37 kDa proteins of the cytoplasm. The 3-aminobenzamide (3-AB) treatment, which decreased ADP-ribosylation, partially reversed SNP-induced inhibition of superoxide generation in macrophages. The above data provide evidence that NO decreases superoxide formation possibly via ADP-ribosylation.

Adenosine Diphosphate↗

PubMed1993

The catalytic domain of human hepatitis delta virus RNA. A proton nuclear magnetic resonance study.

We have obtained and analyzed the 600 MHz proton NMR spectra of a 74-mer RNA derived from the catalytic domain of hepatitis delta virus genomic RNA (HDV RNA) to determine its secondary structure. Deconvolution of the NMR spectrum obtained at 32 degrees C indicates that part of the 74-mer RNA molecule may exist in multiple conformations in equilibrium. The major conformer contains two A-U base pairs and 14 +/- 2 G-C base pairs. It appears to contain no standard G-U base pairs. Our NMR melting study suggests that this conformer has at least two stem-loop regions. One of the regions has been identified to be a tetra-loop. We have assigned five imino proton resonances of the tetra-loop stem. Our data is consistent with the pseudoknot model of Perrotta and Been.

Base Sequence↗

PubMed1993

Growth hormone response to L-dopa and pyridostigmine in women with polycystic ovarian syndrome.

OBJECTIVE: To evaluate the GH secretion and clarify the factors influencing the GH secretion in women with polycystic ovarian syndrome (PCOS). DESIGN: Comparison of the GH response to L-dopa with or without pyridostigmine (inhibitor of acetylcholinesterase) pretreatment and insulin response to oral glucose tolerance test in patients with PCOS and matched controls. SETTING: Outpatients and healthy volunteers studied at a clinical research unit of a university hospital. PATIENTS, PARTICIPANTS: Ten women with PCOS and 9 controls with regular cycles were recruited. INTERVENTIONS: After an overnight fast, each subject underwent a GH stimulation test with L-dopa with or without pyridostigmine pretreatment. Plasma insulin and glucose levels were measured after a 75-g glucose load. MAIN OUTCOME MEASURES: Plasma GH, insulin-like growth factor I (IGF-I), insulin, and nonesterified fatty acids. RESULTS: Growth hormone responses and GH area under the response curve (AUC) to L-dopa were significantly lower in PCOS than those in controls. Pyridostigmine enhanced the GH response to L-dopa significantly in PCOS. Insulin responses and insulin AUC to oral glucose load were significantly higher in PCOS than those in controls. Plasma IGF-I levels of PCOS were significantly higher than controls. Insulin AUC had a positive correlation with plasma IGF-I levels but an inverse correlation with GH AUC in PCOS and controls. CONCLUSION: Our result indicated that decreased GH secretion of PCOS may be associated with a high somatostatin activity and a high plasma IGF-I level.

Adolescent↗

PubMed1993

Properties and regulation of the renal vacuolar H(+)-ATPase and H(+)-K(+)-ATPase.

Two proton-transporting ATPases participate in active proton transport in the nephron: the electrogenic vacuolar H(+)-ATPase and the electroneutral H(+)-K(+)-ATPase. The vacuolar H(+)-ATPase participates in proximal and distal hydrogen ion secretion related to acid-base homeostasis. The H(+)-K(+)-ATPase is located exclusively in the distal nephron, and its primary role may be in active potassium reabsorption. The properties, distribution, and regulation of these two enzymes are discussed.

Animals↗

PubMed1993

Characterization and ontogeny of P1-purinoceptors on rat vas deferens.

1. The P1-purinoceptors which mediate the inhibition by adenosine of nerve-mediated contraction of the rat vas deferens have been investigated by use of the agonists N6-cyclopentyladenosine (CPA) and 5'-N-ethylcarboxamidoadenosine (NECA) and the A1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The ontogeny of the responses to adenosine and to the two co-transmitters which induce the contractions in this tissue, adenosine 5'-triphosphate (ATP) and noradrenaline (NA), have also been studied. 2. The order of potency for the adenosine agonists in inhibiting the nerve-mediated contractions was CPA = NECA > adenosine. Micromolar concentrations of DPCPX were required to antagonize the inhibition by adenosine and NECA of nerve-mediated responses, whereas the inhibitory effect of CPA was antagonized by nanomolar concentrations of the antagonist. 3. NECA and adenosine inhibited contractions induced by ATP (10 microM) or by NA (10 microM), NECA being at least ten fold more potent than adenosine, whereas CPA was inactive. Micromolar concentrations of DPCPX were required to antagonize the effect of adenosine on the contractions induced by ATP (10 microM). 4. Nerve-stimulated contractions could be observed in neonatal tissues from day 15 and increased with age, and could be inhibited by adenosine from this time, the potency of adenosine decreasing with age. Responses to ATP also appeared at day 15 and increased with age up to day 25, while responses to NA were present from day 10 (the earliest day tested) and decreased with age. 5. These results show that the rat vas deferens contains both prejunctional Al-receptors and postjunctional A2-receptors, and that adenosine acts on the latter populations to inhibit nerve-mediated contractions.The high potency of adenosine in the neonate and the parallel development of responses to ATP and to nerve-mediated contractions support suggestions that purinergic responses may be particularly important in neonatal tissues.

Adenosine↗

PubMed1993

Right pulmonary artery arising from ascending aorta: report of a successfully treated case.

A nine-day-old neonate presented with signs of congestive heart failure during the first week of life. The echocardiogram showed an early bifurcating great vessel originating from the left ventricle. In addition, there was another vessel originating from the right ventricle directly connected to the descending aorta without early branching into the bilateral pulmonary arteries. A muscular ventricular septal defect (VSD) was also found. Cardiac catheterization and angiography showed that: 1) the anomalous origin of the right pulmonary artery arose from the ascending aorta; 2) a large patent ductus arteriosus (PDA) connected the main pulmonary artery and the descending aorta; and 3) a muscular VSD existed. Magnetic resonance imaging also demonstrated the above findings. Reimplantation of the anomalous right pulmonary artery to the main pulmonary artery and ligation of the PDA were done. To the best of our knowledge, this very unusual case is the first such neonatal case with successful surgical repair in Taiwan.

Aorta↗