Biomedical subjects

K Lee

Publications and source records attributed to K Lee.

At least 307 records · Page 17Linked to original sources

PubMed1999

Inhibitory effect of munetone, an isoflavonoid, on 12-O-tetradecanoylphorbol 13-acetate-induced ornithine decarboxylase activity.

Starting with an extract derived from the bark of Mundulea sericea Willd. (Leguminosae) that was active in the process of inhibiting 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase activity (ODC) in cultured mouse epidermal ME 308 cells, the isoflavonoid munetone was isolated and identified as an active principle (IC50 = 46 ng/ml). Topical application of munetone (0.04-5 micromol) to the skin of CD-1 mice 2 h prior to treatment with TPA (10 nmol) resulted in dose-dependent inhibition of epidermal ODC activity. In addition, munetone inhibited TPA-independent c-Myc-induced ODC activity with cultured BALB/c c-MycER cells, as well as 7,12-dimethylbenz[a]anthracene (DMBA)-induced preneoplastic lesion formation in a mouse mammary gland organ culture (MMOC) system. These data suggest the potential of munetone to serve as a cancer chemopreventive agent by virtue of blocking the process of tumor promotion.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1999

[Renal and urinary tract abnormalities in small children].

The purpose of this study was to investigate frequency and pattern of urological abnormalities in children younger than two years of age in the county of Frederiksborg, Denmark, with a catchment area of about 350,000 people, and furthermore to investigate in which way the urological abnormalities were diagnosed. From 1994-1996 a total of 35 children younger than two years of age were found to have urological abnormalities. Fourteen patients had a ultrasonographical prenatally diagnosed urological abnormality, which was confirmed postnatally. Twenty-one children were diagnosed with urological abnormalities after presentry with their first urinary tract infection. The obstructive urological diagnoses: congenital hydronephrosis, congenital megaureter and posterior urethral valves made up to 57% (20/35) of the abnormalities. Nine boys were operated upon; three for unilateral hydronephrosis, two for posterior urethral valves, one for unilateral megaureter and three for phimosis. Two girls were treated with oestrogen for labial fusion. Urological abnormalities which were treated were found among the ultrasonographically diagnosed abnormalities, apart from phimosis and labial fusion. The frequency of urological abnormalities was 0.25% in children younger than two years of age in Frederiksborg county. In conclusion, in 1994-1996 the frequency and pattern of urological abnormalities in Frederiksborg county was in accordance with the figures in the literature. Urological abnormalities requiring treatment were diagnosed in 11 children; 55% (6/11) ultrasonographically and 45% (5/11) by examination of the external genitalia of children younger than two years of age at the time of the first diagnosed urinary tract infection.

Abnormalities, Multiple↗

PubMed1999

[T validity of the diagnosis of urinary tract infection in children under two years of age].

In the Department of Paediatrics at Hillerød a valid diagnosis of urinary tract infection in children is defined to be at least 10.000 bacteria/ml. in two midstream specimens of urine or any bacterial growth in urine collected by a suprapubic aspiration or by bladder catheterisation. We decided to study if these criteria were fulfilled in our department, which takes care of urinary tract infections in children in the county of Frederiksborg with a catchment area of about 350.000 people. From 1994-1996 a total of 60 children younger than two years of age were treated for their first suspected urinary tract infection. The diagnosis was valid in 37% of the cases. Eighty-eight percent of the children received parenteral antibiotics for at least three days, and 86% were discharged with prophylactic antibiotics. All underwent urological ultrasonographic examination and 70% underwent an isotope micturition cystourethrography. Among patients with a valid diagnosis 68% were boys and 50% had urological abnormalities, whereas among patients without a valid diagnosis there were 33% boys (p < 0.025) and 24% had urological abnormalities (p = 0.0734). A valid diagnosis of a first urinary tract infection was established in 0.15% of children younger than two years of age in the county of Frederiksborg. This is lower than previously reported. The problem of false positive urinary tract infections thus may be important in general.

Age Factors↗

PubMed1999

Hydrogen peroxide induces intracellular calcium overload by activation of a non-selective cation channel in an insulin-secreting cell line.

Fura-2 fluorescence was used to investigate the effects of H2O2 on [Ca2+]i in the insulin-secreting cell line CRI-G1. H2O2 (1-10 mM) caused a biphasic increase in free [Ca2+]i, an initial rise observed within 3 min and a second, much larger rise following a 30-min exposure. Extracellular calcium removal blocked the late, but not the initial, rise in [Ca2+]i. Thapsigargin did not affect either response to H2O2, but activated capacitive calcium entry, an action abolished by 10 microM La3+. Simultaneous recordings of membrane potential and [Ca2+]i demonstrated the same biphasic [Ca2+]i response to H2O2 and showed that the late increase in [Ca2+]i coincided temporally with cell membrane potential collapse. Buffering Ca2+i to low nanomolar levels prevented both phases of increased [Ca2+]i and the H2O2-induced depolarization. The H2O2-induced late rise in [Ca2+]i was prevented by extracellular application of 100 microM La3+. La3+ (100 microM) inhibited the H2O2-induced cation current and NAD-activated cation (NSNAD) channel activity in these cells. H2O2 increased the NAD/NADH ratio in intact CRI-G1 cells, consistent with increased cellular [NAD]. These data suggest that H2O2 increases [NAD], which, coupled with increased [Ca2+]i, activates NSNAD channels, causing unregulated Ca2+ entry and consequent cell death.

Calcium↗

PubMed1999

Synthesis and biological activity of KCB-328 and its analogues: novel class III antiarrhythmic agents with little reverse frequency dependence.

A series of 3,4-dimethoxyphenethylamine derivatives was prepared, and their prolongation effects on effective refractory period of contractile response (ERPc) and action potential duration (APD) in isolated guinea-pig papillary muscles at 1 Hz and 3 Hz were examined. SAR studies led to the identification of KCB-328 (51) which is a novel class III antiarrhythmic agent with little reverse frequency dependence.

Animals↗

PubMed1999

Immune response enhancement by in vivo administration of B7.2Ig, a soluble costimulatory protein.

The identification of both class I- and class II-restricted tumor-associated peptides recognized by T cells has led to the test of these peptides as immunogens in experimental immunotherapy for cancer patients. However, optimal T cell activation requires signaling both through the T cell receptor for antigen and through costimulatory pathways. B7.1 and B7.2 are powerful costimulatory molecules expressed on the surface of antigen-presenting cells. Using a mouse model, we have sought to optimize costimulatory signals during antipeptide responses by administering a soluble form of B7.2 at the time of peptide immunization. Administration of B7. 2Ig fusion protein significantly enhanced T helper cell and CTL responses. These findings suggest that soluble forms of human B7.2 protein may provide a straightforward and practical method of supplying optimal costimulation during clinical immunotherapy.

Animals↗

PubMed1999

The effects of misleading and inconsistent postevent information on children's recollections of criterion-learned information.

Similar experimental procedures are used in misinformation studies and in retroactive inhibition studies. Despite these similarities, the findings of these studies have suggested that misleading postevent information and inconsistent postevent information would have different effects on children's recollections. To examine this hypothesis, 28 seven-year-olds learned a target game to criterion. Two days later, they were administered either type of postevent information on either one or three occasions. When the children were tested 3 weeks later, the results showed that even criterion-learned information could be affected detrimentally by exposure to misleading or inconsistent postevent information. Notably, children who were administered misinformation on one occasion reported more target information than children in all other groups. It is suggested that exposure to misinformation had a facilitative effect on these children's recollections.

Child↗

PubMed1999

Previously unrecognized obstructive sleep apnea in Chinese subjects with essential hypertension.

Obstructive sleep apnea (OSA) is found to affect 2-4% of the middle-aged population in several Caucasian studies, whereas the prevalence among other ethnic groups have not been clearly documented. It has been reported that OSA and systemic hypertension are highly associated; we therefore conducted a study on Chinese subjects who were receiving treatment for essential hypertension to assess the prevalence of OSA among this group. Ninety-two consecutive patients being followed up at a hypertension clinic were recruited for a questionnaire survey. The entire study group was aged 54.7 +/- 11.7 years, with 40 men. One male subject had a diagnosis of obstructive sleep apnea on nasal continuous positive airway pressure (nCPAP) treatment and 46 subjects agreed to an overnight sleep study. Those who underwent sleep study showed selection bias with a higher body mass index and more symptoms associated with OSA. Of the 46 who underwent sleep study, 16 (34.8%) had an obstructive apnea-hypopnea (AHI) score of >/=5 and excessive daytime sleepiness, with a median score of 26.2 (range, 8.3-64.9). Patients in the group with obstructive sleep apnea syndrome (OSAS) thus defined compared with those without OSAS had more men (64.7 vs 17.20%, p = 0.001) and an excess of smokers (31.5 vs 3.3%. p = 0.01) and had significantly more symptoms of excessive daytime sleepiness (p = 0.001), daytime fatigue (p = 0.007), and witnessed apneas (p = 0.008). Seven patients accepted treatment with nCPAP and reported improvement in symptoms, but there was no detectable change in clinic blood pressure measurements after 3 months of nCPAP treatment. This study demonstrated a high prevalence of previously unidentified OSAS among Chinese patients with essential hypertension. Increased awareness of both doctors and patients toward this potentially treatable problem is warranted.

Adult↗

PubMed1999

Pharmacological characterization of receptor-mediated Ca2+ entry in endothelin-1-induced catecholamine release from cultured bovine adrenal chromaffin cells.

To clarify the mechanism for the endothelin-1 (ET-1)-induced release of catecholamines from the adrenal gland, we examined the effects of removal of extracellular Ca2+, blockers of L-, N-, P- and Q-types of voltage-operated Ca2+ channels (VOCC) such as nifedipine (L-type), omega-conotoxin GVIA (N-type), omega-agatoxin IVA (P-type) and omega-conotoxin MVIIC (Q-type) and blockers of voltage-independent Ca2+ entry channel such as SK&F 96365 and LOE 908 on release of catecholamines, the cytosolic free Ca2+ concentration ([Ca2+]i), and 45Ca2+ uptake in cultured bovine adrenal chromaffin cells. ET-1 but not ET-3 induced increases in release of catecholamines, [Ca2+]i, and 45Ca2+ uptake. The responses to ET-1 were abolished by the antagonist for ET(A) receptors, BQ-123, but not by the antagonist for ET(B) receptors, BQ-788, and they were abolished by removal of extracellular Ca2+. The increases were only partially inhibited (to about 65% of control) by nifedipine but unaffected by any of the omega-toxins. The nifedipine-resistant increase was inhibited by SK&F 96365 (to about 40%) and abolished by LOE 908 alone. These results indicate that ET-1 augments the release of catecholamines from adrenal chromaffin cells through ET(A) receptors, by activating two types of Ca2+ entry channels in addition to L-type VOCC: one (nonselective cation channel-1; NSCC-1) is sensitive to LOE 908 but resistant to SK&F 96365, whereas the other (NSCC-2) is sensitive to both LOE 908 and SK&F 96365.

Acetamides↗

PubMed1999

Cloning and characterization of the mouse interleukin enhancer binding factor 3 (Ilf3) homolog in a screen for RNA binding proteins.

In a screen for RNA-binding proteins expressed during murine spermatogenesis, we have identified a cDNA that encodes a protein of 911 amino acids that contains two copies of the double-stranded RNA-binding motif and has 80% identity with human Interleukin Enhancer Binding Factor 3 (ILF3). Linkage and cytogenetic analyses localized the Ilf3 cDNA to a portion of mouse Chr 9, which shows conserved synteny with a region of human Chr 19 where the human ILF3 gene had been previously localized, supporting that we had cloned the murine homolog of ILF3. Northern analysis indicated the Ilf3 gene is ubiquitously expressed in mouse adult tissues with high levels of expression in the brain, thymus, testis, and ovary. Polyclonal antibodies detected multiple protein species in a subset of the tissues expressing Ilf3 RNA. Immunoreactive species are present at high levels in the thymus, testis, ovary, and the spleen to a lesser extent. The high degree of sequence similarity between the mouse ILF3 protein and other dsRNA binding motif-containing proteins suggests a role in RNA metabolism, while the differential expression indicates the mouse ILF3 protein predominantly functions in tissues containing developing lymphocyte and germ cells.

3' Untranslated Regions↗

PubMed1999

BMP/GDF-signalling interactions during synovial joint development.

The synovial joint arises from an initial condensation of cells that subsequently develops into distinct skeletal structures, separated by the joint. Bone morphogenetic proteins (BMPs) and growth and differentiation factors (GDFs) have a fundamental role during skeletogenesis, including joint formation. Development of the joint appears to be dependent on the differential expression/activity of the related BMP and GDF subfamilies. Gdf-5 is expressed in the developing joints and is necessary for the formation of some joints. In contrast, recent data has shown that antagonism of the BMP family is crucial for joint formation. Here, we review mechanisms of how BMP signalling may be antagonised/modified. We also describe the expression of Bmp-2 and Bmp-4 together with two BMP antagonists, chordin and noggin, during chick joint development. Finally, we discuss possible mechanisms of how a joint forms and the evidence that the joint is a 'signalling centre' that may coordinate the development of adjacent skeletal structures.

Animals↗

PubMed1999

Outcome analysis of external coloanal anastomosis.

BACKGROUND: To evaluate the safety and efficacy of treating low-lying rectal lesions with resection and primary repair using a pull-through technique with rectal stump eversion and external coloanal anastomosis with immediate reintroduction into the pelvis. METHODS: All coloanal anastomoses with the above technique on the Gastrointestinal Surgery Service at the University of Pittsburgh from March 1990 to September 1995 were evaluated. RESULTS: Fifty-two patients underwent coloanal anastomoses with the above technique, and follow-up was available for 96% (50 of 52) of patients. Rectal lesions in the 50 patients included cancer (n = 34), rectal adenomas (n = 13), and other lesions (n = 3). Mean follow-up period was 29.6 +/- 21.8 months (28.5 months for patients with carcinoma). Fecal continence was normal or good in 88% (44 of 50) of patients. Moderate or complete incontinence was present in 12% (6 of 50) of patients. The local recurrence rate of rectal cancer was 0%. Morbidity occurred in 22% (11 of 50) of patients. Survival was 90% (45 of 50 patients). CONCLUSIONS: Coloanal anastomosis with this technique provides effective treatment for low-lying malignant or benign rectal lesions and has an acceptable complication rate.

Anal Canal↗

PubMed1999

Toxicological characterization of sediments from Baie des Anglais on the St. Lawrence Estuary.

The sediments of Baie des Anglais on the St. Lawrence Estuary have a history of environmental contamination, but no information exists relating to their toxicity. The purpose of the present study was to characterize three sites in and near Baie des Anglais, in terms of sediment toxicity and contaminants. Sites 1 and 2 within the Baie des Anglais are relatively close to local industry and municipal sewage discharge points, while Site 3 is outside the bay. Three microscale bioassays, Microtox, echinoderm fertilization and Toxi-ChromoPad, showed that sediments from Site 1 were the most toxic, followed by Site 2. Site 3 was non-toxic. While the solid phase Microtox test did indicate that Site 1 was most toxic, the absolute response was weak. Liver cytochrome P450 1A1 mRNA in American plaice (Hippoglossoides platessoides), captured at Site 1 in the bay was significantly induced compared to the P450 system of plaice captured at Sites 2 and 3. Hepatic metallothionein mRNA levels were not significantly different between plaice captured at all three sites. Sediment chemical analyses revealed a gradient in polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dibenzofurans (PCDF) with the highest levels recorded at Site 1, about 10-fold less at Site 2 and 100-fold less at Site 3. Amongst the organochlorines the PCDF group were deemed the most important due to their prevalence and known toxicity. Heavy metal concentrations were low and representative of background levels for the St. Lawrence Estuary.

Animals↗

PubMed1999

Analysis of gene expression in single cells.

A cell's structural and functional characteristics are dependent on the specific complement of genes it expresses. The ability to study and compare gene usage at the cellular level will therefore provide valuable insights into cell physiology. Such analyses are complicated by problems associated with sample collection, sample size and the limited sensitivity of expression assays. Advances have been made in approaches to the collection of cellular material and the performance of single-cell gene expression analysis. Recent development in global amplification of mRNA may soon permit expression analyses of single cells to be performed on DNA microarrays.

Gene Expression↗

PubMed1999

Chinese children's understanding of false beliefs: the role of language.

The present study investigated the universality of the early development of young children's understanding and representation of false beliefs, and specifically, the effect of language on Chinese-speaking children's performance in false belief tasks under three between-subjects conditions. The three conditions differed only in the belief verb that was used in probe questions regarding one's own or another person's beliefs namely the Chinese verbs, xiang, yiwei, and dang. While the three words are all appropriate to false beliefs, they have different connotations regarding the likelihood of a belief being false, with xiang being more neutral than either yiwei or dang. Experiment 1 involved thirty-five Chinese-speaking adults who responded to false belief tasks to be used in Experiment 2 in order both to establish an adult comparison and to obtain empirical evidence regarding how Chinese-speaking adults use the three belief verbs to describe different false belief situations. In Experiment 2, 188 three-, four-, and five-year-old Chinese-speaking children participated in three false belief tasks. They were asked to report about an individual's false belief when either xiang, yiwei, or dang was used in the probe question. Results revealed a rapid developmental pattern in Chinese-speaking children's understanding of false belief, which is similar to that found with Western children. In addition, children performed significantly better when yiwei and dang, which connote that the belief referred to may be false, were used in belief questions than when xiang, the more neutral verb, was used. This finding suggests an important role of language in assessing children's understanding of belief and false belief.

Adult↗

PubMed1999

Saturable transport of H2-antagonists ranitidine and famotidine across Caco-2 cell monolayers.

The purpose of this study was to investigate the mechanism by which the H2-antagonists ranitidine and famotidine interacted with the paracellular space during their transport across Caco-2 cell monolayers. Transport experiments with ranitidine and famotidine across Caco-2 cell monolayers were performed to determine the apical-to-basolateral flux at various concentrations. Kinetic analysis of the transport data showed that ranitidine and famotidine were transported by both saturable and nonsaturable processes. Na+, K+-ATPase inhibitor ouabain and metabolic inhibitors sodium azide + 2-deoxy-D-glucose did not affect ranitidine transport, suggesting that the active transport was not involved. Famotidine and some other guanidine-containing compounds, e.g., guanethidine, Arg-Gly, L-arginine methyl ester, and L-argininamide, inhibited the transport of ranitidine, whereas other guanidine-containing compounds with an additional negative charge, e.g., L-arginine, did not. 2,4, 6-Triaminopyrimidine (TAP), an inhibitor of paracelluar cationic conductance, also inhibited the transport of both ranitidine and famotidine. On the basis of these results, it is proposed that the saturable transport of ranitidine and famotidine across Caco-2 cell monolayers appears to be via a facilitated diffusion process mediated by the paracellular anionic sites. This mechanism is consistent with the observation that ranitidine and famotidine caused a concentration-dependent increase in transepithelial electrical resistance (TEER) across Caco-2 cell monolayers, presumably by blocking the paracellular anionic sites and thus inhibiting the flux of cations (e.g., Na+).

Biological Transport↗

PubMed1999

Dual chamber implantable cardioverter defibrillator benefits and limitations.

UNLABELLED: Dual chamber ICD capable of providing dual chamber pacing (DDD) and ventricular arrhythmia therapy is now available. We report our experience of clinical performance of dual chamber ICDs amongst Chinese population. METHODS: 9 patients (6 men and 3 women) received dual chamber ICDs, mean age 50 +/- 18.8 years. The indications were ventricular fibrillation (VF) [5], hemodynamic intolerant ventricular tachycardia (VT) [3] and unexplained syncope plus positive induction of VF [1]. The underlying cardiac pathology were congenital LQT syndrome(1), hypertrophic cardiomyopathy [2], coronary artery disease [2], rheumatic valvular disease [1], Brugada syndrome [1], arrhythmogenic right ventricular dysplasia [1] and idiopathic VF [1]. Four patients have documented paroxysmal atrial fibrillation (AF). All patients have defibrillation thresholds (DFT) determined with a binary search protocol starting at 12 joules (J) at implantation. RESULTS: A total of 34 episodes of VF were induced at implantation with mean DFT 13.8 +/- 7 J. The average shocking impedance was 40 +/- 3.6 Omega. The mean acute P wave measured 3.3 +/- 1.3 mV and R wave measured 13.2 +/- 3.2 mV. Atrial and ventricular thresholds, at pulse width 0.5 ms, averaged 0.8 +/- 0.4 V and 0.4 +/- 0.2 V. During follow-up period, 16 episodes of VF were documented and were successfully treated with the first programmed shock. In the patient with LQT syndrome, DDD was initiated to prevent pause-dependant VF. Three episodes of inappropriate therapy (15.8%) were delivered. One patient experienced 2 shocks after exercise. Stored electrograms showed sinus tachycardia with first degree heart block which was misdiagnosed as VT with retrograde 1:1 conduction. Another inappropriate therapy occurred with AF with fast ventricular response within the VF zone and VT therapy inhibitor was disabled. CONCLUSION: Dual chamber ICD allows combined benefits of DDD and VT/VF therapy. Storage of both atrial and ventricular electrograms provide more information in elucidation of nature of dysarrhythmias. Inappropriate shocks, though reduced, are still possible and the rigid algorithms of SVT discrimination from VT will need further published.

Adult↗

PubMed1999

A double-stranded RNA binding protein required for activation of repressed messages in mammalian germ cells.

Chromatin packaging in mammalian spermatozoa requires an ordered replacement of the somatic histones by two classes of spermatid-specific basic proteins, the transition proteins and the protamines. Temporal expression of transition proteins and protamines during spermatid differentiation is under translational control, and premature translation of protamine 1 leads to precocious nuclear condensation and sterility. We have previously suggested that the double-stranded (ds) RNA binding protein Prbp (encoded by the gene Tarbp2) functions as a translational regulator during mouse spermatogenesis. Here we show that Prbp is required for proper translational activation of the mRNAs encoding the protamines. We generated mice that carry a targeted disruption of Tarbp2 and determined that they were sterile and severely oligospermic. Using immunohistological analysis, we determined that the endogenous Prm2 mRNA and a reporter mRNA carrying protamine 1 translational-control elements were translated in a mosaic pattern. We showed that failure to synthesize the protamines resulted in delayed replacement of the transition proteins and subsequent failure of spermiation. The timing of Prbp expression suggests that it may function as a chaperone in the assembly of specific translationally regulated ribonucleoprotein particles.

Animals↗