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Biomedical subjects

Y Lee

Publications and source records attributed to Y Lee.

At least 415 records · Page 23Linked to original sources
PubMed1993

A hospital-based case-control study of breast-cancer risk factors by estrogen and progesterone receptor status.

It has been proposed that breast cancers may differ in their pathogenesis and etiology according to their estrogen receptor (ER) and progesterone receptor (PR) status. This hospital-based case-control study in Japan assessed the relationship between known and suspected breast-cancer risk factors and ER and PR status. Information on risk factors was collected from histologically confirmed breast-cancer cases (n = 519) and from cancer-free controls (n = 9,506). Of 160 cases with known ER status, 58 percent were ER-positive; 38 percent of 157 cases with known PR status were PR-positive. No statistically significant differences were found between ER-positive cf ER-negative cases. However, statistically significant differences between PR-positive cf PR-negative cases were observed for number of full-term pregnancies (P = 0.01), menstrual regularity as a teenager (P = 0.024), and occupation as housewife (P = 0.036). Borderline differences were observed for age at menopause (P = 0.074), and age at menarche (P = 0.083). This study provides some evidence that etiologic distinctions may be greater between PR-positive and PR-negative breast cancers than between ER-positive and ER-negative breast cancers.

Adult↗
PubMed1993

Synthesis and characterization of a bioactive 82-residue sphingolipid activator protein, saposin C.

The sphingolipid activator protein, saposin C (also termed SAP 2), was chemically synthesized, purified, and characterized. The fully protected 82-residue protein was synthesized by automated solid-phase methods, with multiple recoupling steps resulting in a high average coupling efficiency of 98.8%. The overall yield was estimated to be approx 40%. Deprotection and cleavage of the peptide from the resin was followed by folding in the absence of chaotropic agents at pH 8.5. The protein was purified by reversed-phase high pressure liquid chromatography (HPLC) and its purity determined by capillary electrophoresis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The composition of the synthetic saposin C was determined by amino acid analysis. Its sequence was verified by Edman sequence analysis of overlapping peptide fragments generated by chymotryptic and Staphylococcus aureus V8 digestions. The sequence at the C-terminus was determined by digestion with carboxypeptidase P, followed by phenylthiohydantoin (PTH) derivitization and HPLC analysis of the released amino acid residues. Deglycosylated native saposin C appeared as a lower molecular-weight species than synthetic saposin C on SDS-PAGE. This has been explained by amino acid and C-terminal analysis showing native saposin C to be two amino acids shorter at the C terminus than a deduced sequence (from cDNA) previously published. Synthetic saposin C displayed 85% of full biological activity as determined by its ability to stimulate glucocerebrosidase activity in vitro: Synthetic and native saposin C increased glucocerebrosidase catalyzed hydrolysis of 4-methylumbelliferyl beta-D-glucoside by factors of 6.0 and 7.1, respectively. Furthermore, synthetic and native saposin C share similar K(act) values (0.5 and 1.5 microM respectively) indicating that they bind to glucocerebrosidase with similar affinities.

Amino Acid Sequence↗
PubMed1993

Advantages of CT and beam's eye view display to confirm the accuracy of pelvic lymph node irradiation in carcinoma of the prostate.

Possible advantages of computed tomography (CT) and beam's eye view (BEV) display in the design of pelvic irradiation fields were studied in 20 consecutive patients with localized adenocarcinoma of the prostate. Pelvic fields were designed with standard four-field techniques. Then, CT and BEV display were done to define the reduced prostate tumor volumes. With treatment-planning CT, the location of the pelvic vascular structures (internal and external iliac artery and vein) was outlined. These were used as an approximation of the location of the lymph nodes. A BEV display of these lymph node volumes was then compared with the pelvic fields designed without CT and BEV display. Nineteen of the 20 patients had part of the CT-defined lymph node volume (a portion of the internal iliac lymph node volume) excluded from the original field design. Thirteen patients also had part of the external iliac nodal volume excluded. Dose-volume histograms showed that up to 30% of the lymph node volume received only 56% of the prescribed dose.

Adenocarcinoma↗
PubMed1993

Smoking and total mortality: Kangwha cohort study, 6-year follow-up.

The relationship between smoking and total mortality was examined in a community residents population sample of 2,848 men and 3,543 women aged 55 years or over in Kangwha County, Korea during 1985-1991. A total of 1,436 deaths occurred during a 6-year follow-up among the 1.3 fold-higher in current smokers than in non-smokers among men. The relative risk of total mortality was highest for the 55-59 year old age group both in ex-smokers and in current smokers. PAR for total mortality attributed by smoking were estimated to be 26% for ex-smokers and 25% for current smokers in men. The biggest RR (2.1) and PAR (49%) were observed among those who smoked less than 19 cigarettes per day compared to non-smokers in males. Smokers who began to smoke at age 18 or before showed RR 1.8, and PAR 38% in men. Smoking was the most important variable related with total mortality second only to hypertensiveness not including preventable ones among men in multivariate analyses. Men who began to smoke at nineteen years of age or before had RR 1.5 for total cancer mortality. Women showed the similar picture as males in risk factors composition and in relative risks, with a low association strength, however.

Age Factors↗
PubMed1993

Effects of 4'-modified analogs of aristeromycin on the metabolism of S-adenosyl-L-homocysteine in murine L929 cells.

(1'R,2'S,3')-9-(2',3'-Dihydroxycyclopentan-1'-yl)adenine (DHCaA), (1'R,2'S,3'R)-9-(2',3'-dihydroxycyclopentan-1'-yl)-3-deazaadenine (3-deaza-DHCaA), (4'R)-4'-methyl-DHCaA, and (4'R)-4'-vinyl-DHCaA, which are analogs of the carbocyclic nucleoside aristeromycin, were synthesized earlier by our laboratory and were shown to be potent inhibitors of purified bovine liver S-adenosylhomocysteine (AdoHcy) hydrolase (EC 3.3.1.1). In the present study, these analogs were shown to produce rapid (within 15 min) and concentration-dependent (0.03-10 microM) inhibition of AdoHcy hydrolase in cultured murine L929 cells [relative order of inhibitory activity, DHCaA = 3-deaza-DHCaA >> (4'R)-4'-vinyl-DHCaA = (4'R)-4'-methyl-DHCaA]. The relative potencies of these inhibitors on the L929 AdoHcy hydrolase were consistent with their inhibitory effects on the recombinant forms of rat liver and human placental enzymes. This inhibition of L929 cellular AdoHcy hydrolase persisted for up to 48 hr. The inhibition of the L929 AdoHcy hydrolase resulted in a significant increase in the cellular concentrations of AdoHcy, whereas the cellular S-adenosylmethionine (AdoMet) levels remained relatively constant, thereby elevating the AdoHcy/AdoMet ratios. Maximum increases in AdoHcy levels and AdoHcy/AdoMet ratios occurred within 6 hr of exposure to the inhibitors and persisted for at least 24 hr. At a concentration of 1 microM, DHCaA and 3-deaza-DHCaA increased AdoHcy/AdoMet ratios to approximately 0.8 (after 24 hr of exposure to the inhibitors), whereas (4'R)-4'-vinyl-DHCaA and (4'R)-4'-methyl-DHCaA elevated AdoHcy/AdoMet ratios to approximately 0.15, compared with control levels of 0.05. Treatment of L929 cells with concentrations of DHCaA, 3-deaza-DHCaA, (4'R)-4'-vinyl-DHCaA, and (4'R)-4'-methyl-DHCaA up to 10 microM did not result in changes in cellular levels of endogenous nucleotides (e.g., CTP, UTP, ATP, and GTP). In contrast, cells treated with 10 microM aristeromycin for 6 hr contained reduced cellular levels of CTP, ATP, and GTP and significant levels of aristeromycin triphosphate and a GTP metabolite of this carbocyclic nucleoside. These data clearly show that the 4'-modified analogs [DHCaA, 3-deaza-DHCaA, (4'R)-4'-vinyl-DHCaA, and (4'R)-4'-methyl-DHCaA] retain inhibitory activity toward cellular AdoHcy hydrolase, causing elevated levels of AdoHcy and elevated AdoHcy/AdoMet ratios. However, these analogs are devoid of substrate or inhibitory activity toward cellular adenosine kinase. In addition, aristeromycin is rapidly metabolized in murine L929 cell lysates, i.e., > 60% of the aristeromycin had been metabolized in 6 hr. In contrast, neither DHCaA nor 3-deaza-DHCaA showed any decrease in concentration after incubation with cell lysates for up to 6 hr.

Adenosine↗
PubMed1993

[Prognostic significance of auditory brainstem responses in full-term newborn infants with intracranial hemorrhages].

Auditory brainstem response (ABR) was recorded in 41 full-term newborn infants with intracranial hemorrhages (ICH; 10 infants with and 31 infants without neurological sequela) and the data were compared with those obtained in normal full-term newborn infants as controls. The wave-I peak latency was significantly prolonged in the non-sequela group than in the control group and in the sequela group than in the non-sequela group. The wave-III and wave-V peak latencies were significantly prolonged in the ICH group (sequela and non-sequela groups) than in the control group but did not significantly differ between the sequela and non-sequela group. The wave I-V interpeak latency did not significantly differ among the three groups. Among 10 infants in the sequela group, 9 had a V/I amplitude ratio (the amplitude of wave-I divided by the amplitude of wave- V) of less than 1.0. This suggests that the V/I amplitude ratio is of prognostic value in ICH infants.

Cerebral Hemorrhage↗
PubMed1992

Unbalanced ribosome assembly in Saccharomyces cerevisiae expressing mutant 5 S rRNAs.

Mutant 5 S rRNA genes were expressed in Saccharomyces cerevisiae to further define the function of the ribosomal 5 S RNA. RNA synthesis and utilization were assayed using previously constructed markers which have been shown to be functionally neutral and easily detected by gel electrophoresis. Most mutations were found not to affect the growth rate because they were poorly expressed or could be accommodated effectively in the ribosomal structure. Two of the mutants, Y5A99U56U57 and Y5U90i5 adversely affected cell growth as well as protein synthesis in vitro. Polyribosome profiles in both of these mutants were substantially shorter, and an analysis of the ribosomal subunit composition revealed a significant imbalance with a 25-35% excess in 40 S subunits. Kinetic analyses of RNA labeling indicated very low cellular levels of mutant RNA either because it was poorly expressed (Y5U90i5) or rapidly degraded before being incorporated into mature 60 subunits (Y5A99U56U57). The results suggest that the 5 S RNA is required for the assembly of stable ribosomal 60 S subunits and raise the possibility that this RNA or, more likely, its corresponding ribonucleoprotein complex is critical for subunit assembly or even RNA processing.

Base Sequence↗
PubMed1992

Alteration of RNA I metabolism in a temperature-sensitive Escherichia coli rnpA mutant strain.

E. coli strain A49 carries the themosensitive mutation in the rnpA gene encoding the protein component of RNase P, a tRNA-processing enzyme. Two small RNAs were highly accumulated in the A49 carrying derivatives of ColE1-type plasmids, at nonpermissive temperature. Characterization of these RNAs showed that they were the processed or degraded products derived from RNA I, which is the negative controller of ColE1-type plasmid replication. These derivatives of RNA I only differ in size at the 5' ends. The data of their degradation and synthesis kinetics suggest that they are intermediates of RNA I metabolism.

Base Sequence↗
PubMed1992

Localization of basic fibroblast growth factor-like immunoreactivity in the rat brain.

The immunohistochemical localization of basic fibroblast growth factor (bFGF) was studied in the adult rat brain, using a specific antibody against a synthetic bFGF fragment (the N-terminal 12 residues). Widespread but uneven regional localization of bFGF-like immunoreactive neurons and fibers was observed. Ependymal cells were also stained. The immunoreactive neurons were found in the cerebral cortex, olfactory bulb, septum, basal magnocellular nuclei, thalamus, hypothalamus, globus pallidus, hippocampus, amygdala, red nucleus, central gray of the midbrain, cerebellum, dorsal tegmental area, reticular formation, cranial motor nuclei and spinal cord. Immunoreactive fiber bundles and nerve terminals were also detected. These results indicate that bFGF is produced by or present in a specific neuronal cell population of the central nervous system.

Amino Acid Sequence↗
PubMed1992

Nucleic acid related compounds. 74. Synthesis and biological activity of 2'(and 3')-deoxy-2'(and 3')-methylenenucleoside analogues that function as mechanism-based inhibitors of S-adenosyl-L-homocysteine hydrolase and/or ribonucleotide reductase.

Treatment of 2-amino-6-chloro-9-(beta-D-ribofuranosyl)purine (21) with TBDMS chloride/imidazole/DMF gave a separable mixture of 5'-O, 2',5'-bis-O (22), 3',5'-bis-O (23), and 2',3',5'-tris-O-TBDMS derivatives. Oxidation of 22 and 23 with CrO3/pyridine/Ac2O, treatment of the respective ketonucleosides with methylenetriphenylphosphorane, and deprotection gave 2-amino-6-chloro-9-[3(and 2)-deoxy-3(and 2)-methylene- beta-D-erythro-pentofuranosyl]purines (28 and 37) that were converted into other 2-amino-6-substituted-purine analogues. Tubercidin was converted into 2'-deoxy-2'-methylenetubercidin (49) by an analogous route. Inactivation of S-adenosyl-L-homocysteine hydrolase by 2'- and 3'-methyleneadenosine analogues was investigated. Mechanism-based inhibition of S-adenosyl-L-homocysteine hydrolase and anticancer and antiviral activities of 2'(and 3')-deoxy-2'(and 3')-methylenenucleoside analogues are discussed.

Adenosylhomocysteinase↗
PubMed1992

Insertion and folding of the amino-terminal amphiphilic signal sequences of the mannitol and glucitol permeases of Escherichia coli.

Peptides which correspond to the NH2-terminal 23 or 22 residues of the mannitol and glucitol permeases (enzymes IImtl and IIgut of the bacterial phosphotransferase system; mtl-23 and gut-22) and which are believed to function in envelope targeting were synthesized chemically, and their interactions with lipid model membranes were studied. Both wild-type peptides penetrated phospholipid monolayers up to high surface pressures, and partition constants of 8.0 x 10(4) M-1 and 4.2 x 10(4) M-1, respectively, were derived from the incorporation isotherms of mtl-23 and gut-22 with monolayers of 1-palmitoyl-2-oleoyl-3-sn-phosphatidylcholine at 32 mN/m or bilayers of the same lipid. The mtl-23 peptide was highly alpha-helical in trifluoroethanol, sodium dodecyl sulfate, lysolecithin, or vesicles of 1-palmitoyl-2-oleoyl-3-sn-phosphatidylglycerol, with estimated percentages of alpha-helix ranging between 60 and 85%. The interactions with model membranes of several single site mutants (S3P, D4P, and D4K) of mtl-23 which were defective in properly assembling the mannitol permease in the cytoplasmic membrane of Escherichia coli were also studied. The contents of alpha-helix of these peptides in detergent micelles or phospholipid bilayers were not significantly changed compared with those of the wild type, suggesting that the amphiphilic NH2-terminal membrane-targeting domain could still be formed in these mutants. However, the mutants which contained a proline in positions 3 or 4, i.e. NH2-terminal to the proposed amphiphilic alpha-helix, partitioned into phospholipid monolayers with partition constants that were 2 or 4 times smaller than those of the wild type. Based on these data, a model of the amphiphilic structure of the NH2-terminal domain of the mannitol permease is discussed. This domain may interact physiologically with amphiphilic interfaces of lipids and/or proteins during membrane insertion.

Amino Acid Sequence↗
PubMed1992

4'-modified analogues of aristeromycin and neplanocin A: synthesis and inhibitory activity toward S-adenosyl-L-homocysteine hydrolase.

The carbocyclic adenosine analogues aristeromycin and neplanocin A both display significant S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitory activity and broad-spectrum antiviral effects. Since phosphorylation of the 4'-hydroxymethyl substituent has been implicated with the cytotoxicity of these compounds, various analogues modified at this position were synthesized utilizing a key cyclopentenone intermediate 3 which can be derived from several members of the natural chiral pool. Cyclopentenone 3 underwent a highly stereoselective conjugate addition with organocuprate reagents, and the 1,4-adducts so formed were then readily elaborated to the corresponding 4'-modified aristeromycin analogues. Alternatively, quenching the enolate intermediate of the organocuprate conjugate addition with methanesulfinyl chloride followed by pyrolytic syn elimination resulted in the formation of 4'-modified neplanocin A intermediates. Three of the final compounds (1b, 1c, and 1e) displayed inhibitory activity toward AdoHcy hydrolase in the nanomolar range.

Adenosine↗
PubMed1992

Suppression of human nasopharyngeal carcinoma cell growth in nude mice by the wild-type p53 gene.

Wild-type and mutant human p53 genes were transfected into the nasopharyngeal carcinoma (NPC) cell line CNE-3. Tumorigenicity in nude mice showed that the tumor resulting from the cells transfected with the wild-type p53 gene grew more slowly and was smaller than that from the cells transfected with mutant p53 gene and that from control CNE-3 cells. In contrast, the tumor from the cells transfected with the mutant p53 gene grew faster than that produced by cells transfected with the wild-type p53 gene and that produced by control CNE-3 cells. The results demonstrate that the wild-type p53 gene could inhibit the NPC cell growth in nude mice and the mutant p53 gene could enhance the NPC cell growth in nude mice. The p53 gene may also play an important role in the pathogenesis of NPC.

Animals↗
PubMed1992

Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors.

The MEF2 site is an essential element of muscle enhancers and promoters that is bound by a nuclear activity found, so far, only in muscle and required for tissue-specific transcription. We have cloned a group of transcription factors from human muscle that are responsible for this activity: They are present in muscle-specific DNA-binding complexes, have a target sequence specificity identical to that of the endogenous activity, and are MEF2 site-dependent transcriptional activators. These MEF2 proteins comprise several alternatively spliced isoforms from one gene and a related factor encoded by a second gene. All share a conserved amino-terminal DNA-binding domain that includes the MADS homology. MEF2 transcripts are ubiquitous but accumulate preferentially in skeletal muscle, heart, and brain. Specific alternatively spliced isoforms are restricted to these tissues, correlating exactly with the presence of endogenous MEF2 activity. Furthermore, MEF2 protein is detected only in skeletal and cardiac muscle nuclei and not in myoblast and nonmuscle cells. Thus, post-transcriptional regulation is important in the generation of tissue-specific MEF2 activity. Cardiac and smooth, as well as skeletal, muscles contain functionally saturating levels of MEF2 trans-activating factors that are absent in nonmuscle cells. Moreover, MEF2 is induced in nonmuscle cells by MyoD; however, MEF2 alone is insufficient to produce the full muscle phenotype. Implications for the molecular mechanisms of myogenesis are considered.

Amino Acid Sequence↗
PubMed1992

Determination of serum unbound bilirubin for prediction of kernicterus in low birthweight infants.

Serum unbound bilirubin concentrations (UBC) and serum total bilirubin concentrations (TBC) were measured serially in 138 low birthweight (LBW) infants treated with phototherapy for non-hemolytic hyperbilirubinemia. We attempted to assign the suitable critical UBC levels for predicting bilirubin encephalopathy into two different birthweight groups: a very low birthweight (VLBW) group (birthweight < 1,500 g) and an LBW group (birthweight between 1,500 g and 2,499 g). Twelve infants were diagnosed as 'at risk' for kernicterus, of whom 11 had signs of acute bilirubin encephalopathy and received exchange transfusion. One VLBW infant had neurological sequelae at a 3 year follow-up, although exchange transfusion was not carried out because of low TBC. Sensitivity and specificity for predicting kernicterus were calculated at different UBC levels between 0.6 microgram/dl and 1.5 micrograms/dl and TBC levels between 8 mg/dl and 26 mg/dl. The receiver-operating characteristic (ROC) curves plotted for UBC as a predictor of kernicterus were clearly shifted up and to the left compared with the curves for TBC in the VLBW and LBW groups. Thus, the UBC measurement may well provide a more rational basis for evaluating the risk of kernicterus in LBW infants. The optimal cut-off points were derived from these curves. In the VLBW group, the sensitivity was 100% and the specificity was 96% for a UBC of 0.8 microgram/dl, and 80% and 64% for a TBC of 11 mg/dl. In the LBW group, the sensitivity was 100% and the specificity was 98% for a UBC of 1.0 microgram/dl and 71% and 78% for a TBC of 16 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Bilirubin↗
PubMed1992

Involvement of SecB, a chaperone, in the export of ribose-binding protein.

Ribose-binding protein (RBP) is an exported protein of Escherichia coli that functions in the periplasm. The export of RBP involves the secretion machinery of the cell, consisting of a cytoplasmic protein, SecA, and the integral membrane translocation complex, including SecE and SecY. SecB protein, a chaperone known to mediate the export of some periplasmic and outer membrane proteins, was previously reported not to be involved in RBP translocation even though small amounts of in vitro complexes between SecB and RBP have been detected. In our investigation, it was shown that a dependence on SecB could be demonstrated under conditions in which export was compromised. Species of RBP which carry two mutations, one in the leader that blocks export and a second in the mature protein which partially suppresses the export defect, were shown to be affected by SecB for efficient translocation. Five different changes which suppress the effect of the signal sequence mutation -17LP are all located in the N domain of the tertiary structure of RBP. All species of RBP show similar interaction with SecB. Furthermore, a leaky mutation, -14AE, generated by site-specific mutagenesis causes reduced export in the absence of SecB. These results indicate that SecB can interact with RBP during secretion, although it is not absolutely required under normal circumstances.

Bacterial Proteins↗