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H Lee

Publications and source records attributed to H Lee.

At least 379 records · Page 21Linked to original sources
PubMed1999

[Quantification of cerebral blood flow using 123I-IMP SPECT--a new method of estimating the input function from brain dynamic data].

In order to avoid continuous arterial blood sampling, we estimated input function by the method in that the whole brain time activity curves were fitted by two-term exponential function and differentiated analytically after the injection of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP). This method was applied to 4 patients with cerebral infarction and 2 patients with brain tumor. Values of regional cerebral blood flow (rCBF) were calculated from the input function calibrated by one-point arterial sampling at 5 minutes after the injection using microsphere method, and then were compared with those obtained from the table-lookup method. In this study, we used the individual input function for the table-lookup method instead of the standard input function. The overall accuracy errors between two-term exponential functions and the whole brain time-activity curves were about 1%. The values of rCBF calculated by this method were well correlated with those by the table-lookup method (r = 0.901, p < 0.001). Optimal calibration time for this method was between 3-minute and 10-minute after 123I-IMP injection and the deviation of the rCBF values obtained by this method from those obtained by the table-lookup method in which the input function was calibrated at 5 minutes remained within 10%. This method is a less invasive and convenient alternative to the conventional methods which require continuous arterial blood sampling.

Adult↗
PubMed1999

Lysophosphatidic acid as a regulator of endothelial/leukocyte interaction.

Lysophosphatidic acid (LPA) is produced by a variety of activated cell types and acts as an intercellular mediator of processes associated with inflammation and repair including platelets aggregation, and smooth muscle and fibroblast proliferation. However no previous studies have examined the effects of LPA on endothelial cell leukocyte interactions. We have examined the ability of LPA to activate human aortic endothelial cells (HAEC) to bind monocytes, neutrophils, and HL60 cells (a neutrophil surrogate). Treatment of HAEC for 4 hours with 10 microM LPA caused an increase in the binding of monocytes, neutrophils, and HL60. LPA but not phosphatidic acid dose-dependently increased E-selectin and vascular cell adhesion molecule-1 (VCAM-1) cell surface expression. We performed several studies to characterize the receptor mediating the LPA effect. We demonstrate that at least five potential LPA receptors are expressed by HAEC: Edg-1, -3, -4, and -5 as well as PSP24. Cyclic phosphate-containing phosphatidic acid analogue, an agonist for the type 3 low affinity LPA receptor, was not effective in activating HAEC to bind leukocytes, excluding a role for this receptor. The selective receptor antagonists N-palmitoyl-serine and N-palmitoyl-tyrosine (which inhibits PSP24) completely inhibited LPA-induced VCAM expression; however these antagonists inhibited E-selectin expression by only 30%, suggesting a role for at least one additional LPA receptor mediating E-selectin expression. We propose that Edg-1 might be the second receptor, because this receptor, when expressed in HEK293 cells, similarly to the PSP24 receptor, caused ERK activation to nanomolar concentration of LPA. Exposure of HAEC to sphingosine-1-phosphate, another Edg-1 receptor agonist, increased surface expression of E-selectin and to a much smaller extent VCAM-1. The effects of both LPA and sphingosine-1-phosphate on the induction of both VCAM-1 and E-selectin expression was abolished by pretreatment with pertussis toxin suggesting that both LPA receptors in HAEC couple to a Gi pathway. These findings reveal an important and novel role for LPA and its receptors in inflammatory processes.

Animals↗
PubMed1999

The diagnosis and treatment of metastatic spinal tumor.

Metastases to the spine represent a challenging problem in an oncology practice. Treatment decisions require multidisciplinary review. Radiation therapy remains the primary treatment for metastatic spinal tumor, but advances in radiation therapy, chemotherapy, and surgery have changed the roles of each and lead to improved patient outcomes. Regardless of the treatment, diagnosis and treatment before the development of significant neurologic and functional deficits improve outcomes. Physician awareness and appropriate imaging greatly assist in the early detection of tumor.

Humans↗
PubMed1999

Degradation of 2,4-dinitrophenol and selected nitroaromatic compounds by Sphingomonas sp. UG30.

Sphingomonas strain UG30 mineralizes both p-nitrophenol (PNP) and pentachlorophenol (PCP). Our current studies showed that UG30 oxidatively metabolized certain other p-substituted nitrophenols, i.e., p-nitrocatechol, 2,4-dinitrophenol (2,4-DNP), and 4,6-dinitrocresol with liberation of nitrite. 2,6-DNP, o- or m-nitrophenol, picric acid, or the herbicide dinoseb were not metabolized. Studies using 14C-labelled 2,4-DNP indicated that in glucose-glutamate broth cultures of UG30, greater than 90% of 103 microM 2,4-DNP was transformed to other compounds, while 8-19% of the 2,4-DNP was mineralized within 5 days. A significant portion (20-50%) of the 2,4-DNP was metabolized to highly polar metabolite(s) with one major unidentified metabolite accumulating from 5 to 25% of the initial radioactivity. The amounts of 2,4-DNP mineralized and converted to polar metabolites was affected by glutamate concentration in the medium. Nitrophenolic compounds metabolized by UG30 were also suitable substrates for the UG30 PCP-4-monooxygenase (pcpB gene expressed in Escherichia coli) which is likely central to degradation of these compounds. The wide substrate range of UG30 could render this strain useful in bioremediation of some chemically contaminated soils.

2,4-Dinitrophenol↗
PubMed1999

Molecular genotyping of HIV-1 in 61 patients with AIDS from Lomé, Togo.

To study the distribution of HIV types and genotypes, in Lomé, Togo, a random population of patients who met the clinical criteria of the Bangui definition of AIDS and were positive with two independent screening assays for antibodies to HIV-1 group M, HIV-2, and HIV-1 group O was selected. HIV RNA from serum samples was reverse-transcribed and amplified with degenerate primers annealing to conserved regions of the HIV-1, HIV-2, and HIV-O gag gene. Amplicons were directly sequenced using an automated sequencer. A 262-271-bp (strain-dependent) fragment of the gag gene from each patient was phylogenetically analyzed and compared to the corresponding gag sequences of published HIV-1 sequences of known African genotypes. Genotype A was found in 48 of 60 patient amplicons (80%), subdivided into two clusters. Ten patients (16.7%) were HIV-1 genotype G; one was genotype D and one genotype H. HIV-1 genotype B was not found. Amplicons from two patients contained sequence ambiguities, requiring cloning and sequencing of the gag insert. One patient (T52) was apparently infected with HIV-1 genotypes A and G; whereas HIV-1 from patient T139 was of genotype A, with 2/10 clones having a three-codon insertion at nucleotide position 1142 of the gag gene. HIV-1 genotype A is dominant in Togo; genotype G is frequent and genotype B has not been found.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Biphenylsulfonamide endothelin antagonists: structure-activity relationships of a series of mono- and disubstituted analogues and pharmacology of the orally active endothelin antagonist 2'-amino-N- (3,4-dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1, 1'-biphenyl]-2-sulfonamide (BMS-187308).

Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4'-position. Introduction of an amino group at the 2'-position also led to improved analogues. Combination of the optimal 4'-isobutyl substituent with the 2'-amino function afforded an analogue (20, BMS-187308) with improved ETA binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 micromol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.

Administration, Oral↗
PubMed1998

MUC1 is a novel marker for the type II pneumocyte lineage during lung carcinogenesis.

Abnormalities in mucin-type glycoprotein expression have been documented in a variety of cancers, identifying these molecules as targets for immunologically based therapies and prognostic/diagnostic assays. We examined the expression of the membrane-bound MUC1 mucin in normal, histologically atypical, and neoplastic lung to determine its potential contribution to lung carcinogenesis. In vivo, intense MUC1 immunoreactivity was present in normal type II pneumocytes as well as in a range of atypical lesions derived from type II cells and >60% of primary and metastatic non-small cell lung cancers. Expression was not associated with altered survival, although it was highly correlated with the adenocarcinoma histology. A carcinogenesis model using 4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone-exposed hamsters revealed that MUC1 mRNA increased prior to the histological appearance of tumors. In vitro studies using MUC1 expressing non-small cell lung cancer cell lines revealed that differentiation away from a type II cell lineage was associated with dramatic down-regulation of MUC1. We propose that MUC1 is a powerful new marker for the type II pneumocyte cell lineage that allows us to follow the type II pneumocyte lineage during the process of lung carcinogenesis.

Animals↗
PubMed1998

Inhibition of colonization and cell-matrix adhesion after nm23-H1 transfection of human prostate carcinoma cells.

A human gene, nm23-H1, has been known as a metastasis suppressor in many tumor cells. The cellular mechanisms by which the nm23-H1 protein may directly or indirectly modulate the metastatic phenotype are not yet known. In this study the phenotypic effect of transfection of nm23-H1 cDNA into the human DU 145 prostate carcinoma cell line was examined. Despite similar growth rates, the nm23-H1-transfected lines displayed decreased colonization in soft agar and adhesion to extracellular matrix components when compared with the control transfected line. The results suggest that the nm23-H1 gene product suppresses the metastatic potential of prostate carcinoma cells by inhibiting their ability in anchorage-independent growth and extracellular matrix adhesion.

Carcinoma↗
PubMed1998

Increased levels of cigarette use among college students: a cause for national concern.

CONTEXT: Adolescent smoking prevalence is tracked annually and has increased since 1991. In contrast, little is known about trends in smoking among college students, a group that has previously been more resistant to tobacco use than other young adults. OBJECTIVE: To examine changes in cigarette smoking among college students between 1993 and 1997 and among different types of students and colleges. DESIGN: Self-administered survey (Harvard School of Public Health College Alcohol Study). SETTING: One hundred sixteen nationally representative 4-year colleges. SUBJECTS: A total of 15103 randomly selected students in 1993 (70% response rate) and 14251 students in 1997 (60% response rate). MAIN OUTCOME MEASURES: Self-reports of cigarette smoking in the past 30 days and in the past year, age at smoking first cigarette, and number of attempts to quit. RESULTS: Over 4 years, the prevalence of current (30-day) cigarette smoking rose by 27.8%, from 22.3% to 28.5% (P<.001). The increase was observed in 99 of 116 colleges and was statistically significant (P<.05) in 27 (23%) of them. Current smoking increased across all student subgroups (defined by sex, race/ethnicity, and year in school) and in all types of colleges. Smoking is rising faster in public schools (from 22.0% to 29.3%) than in private schools (from 22.9% to 26.8%). Eleven percent of college smokers had their first cigarette and 28% began to smoke regularly at or after age 19 years, by which time most were already in college. Half of current smokers tried to quit in the previous year; 18% had made 5 or more attempts to quit. CONCLUSIONS: Cigarette use is increasing on campuses nationwide in all subgroups and types of colleges. Substantial numbers of college students are both starting to smoke regularly and trying to stop. National efforts to reduce smoking should be extended to college students.

Adolescent↗
PubMed1998

Synthesis and in vitro cytotoxicity of 3-substituted-1,8-diazaanthraquinones produced by Lewis-acid catalyzed hetero Diels-Alder reaction.

A hetero Diels-Alder reaction of quinoline-5,8-dione with 1-(N,N-dimethylamino)-3-methyl-1-aza-1,3-butadiene proceeded to give 3-methyl-1,8-diazaanthraquinone (100% regioselectivity) in the presence of Lewis-acid catalyst (ZnCl2 or ZnBr2). Subsequent functionalizations of the benzylic methyl group resulted in the 1,8-diazaanthraquinone analogues as potential antitumor agents. The most active compound, 8, exhibited in vitro cytotoxic activity comparable to that of doxorubicin.

Anthraquinones↗
PubMed1998

Gonadotropin-releasing hormone (GnRH) gene regulation by N-methyl-D-aspartic acid in GT1-1 neuronal cells: differential involvement of c-fos and c-jun protooncogenes.

The present study examined the regulatory mechanisms of GnRH gene expression by N-methyl-d-aspartic acid (NMDA) in immortalized hypothalamic GnRH neurons (GT1-1 cells). NMDA (100 microM) stimulated GnRH mRNA levels transiently at 2 h after treatment. Dose-response experiment showed that there was a biphasic action of NMDA on GnRH mRNA levels: GnRH mRNA levels were increased by NMDA at lower concentrations (10 and 100 microM), but not at higher concentrations (1 and 10 mM). NMDA (100 microM)-induced GnRH mRNA levels were efficiently blocked by pre-treatment with NMDA receptor antagonists, MK-801 and AP-5. We next examined the signal transduction pathways involved in NMDA-induced GnRH gene expression based on previous findings that NMDA signal propagates into the cell through Ca2+ and nitric oxide (NO) pathways in many neurons. While ionomycin, a Ca2+ ionopore, application failed to alter GnRH gene expression, treatment of GT1-1 cells with sodium nitroprusside (SNP), an NO donor, increased GnRH gene expression with a similar time course to NMDA treatment. Moreover, application of GT1-1 cells with nitric oxide synthase (NOS) inhibitors (l-NAME, d-NAME, and NA) prior to NMDA treatment, inhibited NMDA-induced GnRH gene expression. These results indicate that the effect of NMDA is mediated by the NO signalling cascade. The mouse GnRH promoter activity was also increased by NMDA at low concentration (100 microM), but not at high concentration (1 microM), confirming the biphasic action of NMDA on GnRH mRNA levels. Since NMDA (100 microM) and SNP (1 microM) markedly induced c-jun expression, but not c-fos expression, we hypothesized that Jun activation is responsible for the transcriptional activation of GnRH gene expression. To examine this, we performed two different experiments. Treatment of NMDA greatly increased the activity of heterologous promoter of Fos/Jun responsive sequence (-187/-69) from the mouse GnRH promoter fused to hsv-tk minimal promoter. Moreover, overexpression of c-jun induced GnRH promoter activity, while c-fos overexpression decreased GnRH promoter activity. Taken together, this study indicates that NMDA regulates GnRH gene expression in GT1-1 cells through the NO-Jun signal transduction pathway.

Animals↗
PubMed1998

Striatal enlargement in rats chronically treated with neuroleptic.

BACKGROUND: Striatal enlargement with chronic neuroleptic treatment in schizophrenic patients has been reported by several investigators. Longitudinal magnetic resonance imaging studies of patients suggest that changes in striatal volume may be caused by treatment with antipsychotic medication. METHODS: We have examined the effects of chronic neuroleptic treatment on postmortem striatal volume in the laboratory rat and have examined the relationship between striatal volume and vacuous chewing movements (VCMs). Autoradiographs of 50 rats treated with haloperidol (1.5 mg/kg/day) or drug free for varying durations of time (1-12 months) were utilized in this analysis. RESULTS: Chronic treatment with neuroleptics (1 month or greater) was associated with larger striatal volumes. The increase in striatal volume was present at 1 month of treatment and was sustained to 12 months of treatment. Rats that developed the high-VCM syndrome had larger striatal volumes than both drug-free and low-VCM rats, while low-VCM rats had larger striatal volumes than drug-free rats. CONCLUSIONS: These data suggest that chronic neuroleptic treatment is the cause of striatal enlargement in the laboratory rat, and that this enlargement is most prominent in rats that have the high-VCM syndrome.

Animals↗
PubMed1998

Amygdalar NMDA receptors are critical for new fear learning in previously fear-conditioned rats.

NMDA receptors in the amygdala seem to be critical for fear conditioning in naive rats. Recent spatial-learning studies suggest that previous learning protected animals from the amnesic effect of NMDA antagonists on new learning (of a similar behavioral task). Therefore, the present study examined whether blocking of NMDA receptors in the basolateral nucleus of the amygdala (BLA) prevents new fear learning in previously fear-conditioned rats, as measured by freezing behavior. Intra-BLA infusions of the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) completely blocked fear conditioning to a tone stimulus in animals that had previously been fear-conditioned to a light stimulus. Similar results were obtained with intra-BLA infusions of APV before contextual fear conditioning in rats that had been fear-conditioned to a different context. Additional experiments showed that intra-BLA APV infusions substantially interfere with the expression and extinction of conditioned fear to tone, light, and context stimuli. Together, these results indicate that NMDA receptors in the BLA are crucial for the encoding of new fear memories (i.e., the formation of specific conditioned stimulus-unconditioned stimulus association), the expression of conditioned fear responses, and the extinction of acquired fear.

Acoustic Stimulation↗
PubMed1998

CDK inhibitors p18(INK4c) and p27(Kip1) mediate two separate pathways to collaboratively suppress pituitary tumorigenesis.

INK4 and CIP/KIP are two distinct families of cyclin-dependent kinase (CDK) inhibitors implicated in mediating a wide range of cell growth control signals. We have created p18(INK4c)-deficient mice. These mice develop gigantism and widespread organomegaly. The pituitary gland, spleen, and thymus are disproportionately enlarged and hyperplastic. T and B lymphocytes develop normally in p18-deficient mice, but both exhibit increased cellularity and a higher proliferative rate upon mitogenic stimulation. Loss of p18, like that of p27, but not other CDK inhibitor genes, leads to a gradual progression from intermediate lobe pituitary hyperplasia in young mice to an adenoma by 10 months of age with a nearly complete penetrance. Mice lacking both p18 and p27, like mice chimeric for Rb deficiency, invariably died from pituitary adenomas by 3 months. Hence, p18 and p27 mediate two separate pathways to collaboratively suppress pituitary tumorigenesis, likely by controlling the function of Rb.

Adenoma↗
PubMed1998

Radiographic findings and morbidity in patients treated with stereotactic radiosurgery.

PURPOSE: To determine the prognostic significance of pretreatment edema, lesion size and location on morbidity following stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Forty-seven evaluable patients with 63 lesions were treated on a 6-MV linear accelerator radiosurgery system at Memorial Sloan Kettering Cancer Center. All patients received a 10-mg intravenous bolus of dexamethasone sodium phosphate (Decadron) prior to SRS. Thirteen patients were treated for asymptomatic lesions while 34 were treated because of neurologic symptoms. The median dose delivered was 1800 cGy and the median prescription isodose curve was 85%. Pretreatment edema was measured on a transaxial T2-weighted MR image acquired within 1 month of the SRS. RESULTS: Ten patients experienced morbidity as a result of their treatment. The complication rate was measured by neurologic events following SRS and was not significantly influenced by the extent of peritumoral edema. Lesion size was also unrelated to the development of post-treatment symptoms as assessed by the ease of tapering steroids. The only parameter found to influence post-SRS complications was lesion location. Four of six (66%) patients treated to lesions in the motor cortex suffered post-SRS seizure activity, whereas only 6 of 37 (16%) patients treated to lesions elsewhere in the brain parenchyma experienced seizure activity. CONCLUSION: The presence of pretreatment edema and lesion size are not predictors of post-SRS complication rates or the ability to taper Decadron. Lesion location is predictive of post-SRS seizure activity.

Adolescent↗
PubMed1998

Exon-intron structure of the human PTK6 gene demonstrates that PTK6 constitutes a distinct family of non-receptor tyrosine kinase.

Partial PTK6 (also known as Brk) cDNA was initially isolated by reverse transcription-PCR of normal human melanocyte mRNAs and the full-length cDNA encodes a non-receptor protein tyrosine kinase with an SH3 domain, an SH2 domain, and a kinase catalytic domain. We have cloned the human PTK6 gene by screening human genomic lambda libraries using the full-length PTK6 cDNA as probe. The human PTK6 gene consists of 8 exons encompassing 8.8 kb and all the splicing junctions followed the conserved GT/AG rule. Coding sequence of the PTK6 gene was identical to that of the cDNA cloned from T-47D, human breast tumor cell line. Although the amino acid sequence of the PTK6 polypeptide showed the strongest homology to those of the Src family members of protein tyrosine kinases, exon-intron boundaries of the PTK6 gene were quite different from those of the Src family genes, which are evolutionarily conserved. The 813-bp 5'-flanking sequence of the PTK6 gene upstream of a luciferase reporter gene conferred significant promoter activity, at approximately 60% level of the SV40 promoter, in transient expression assays into MCF-7, human breast tumor cell line. PTK6 mRNA was expressed at very high level in colon and at high levels in small intestine and prostate, and at low levels in some tested fetal tissues. These results suggest that PTK6 constitutes an evolutionarily distinct family of non-receptor protein tyrosine kinases and may function as an intracellular signal transducer in specific tissues.

Base Sequence↗
PubMed1998

Alteration of the substrate range of haloalkane dehalogenase by site-directed mutagenesis.

We attempted to expand the range of chlorinated solvents degraded by Xanthobacter autotrophicus GJ10 to include trichloroethylene by the rational modification of the enzyme haloalkane dehalogenase. The amino acids Phe164, Asp170, Phe172 and Trp175 were individually replaced with alanine by site-directed mutagenesis. All substitutions produced enzymes with lower than wild type activity with 1,2-dichloroethane. The Phe164Ala and Asp170Ala mutants were 3 and 2 times more active than was the wild type enzyme in dechlorinating 1,6-dichlorohexane. The Asp170Ala mutant resembled the wild type enzyme in its relative activity against longer chain substrates. No mutant was active with trichloroethylene.

Alanine↗