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Biomedical subjects

S Lee

Publications and source records attributed to S Lee.

At least 955 records · Page 53Linked to original sources
PubMed1995

The relationship between systolic pressure and stroke volume describes myocardial contractility.

OBJECTIVE: To develop a method of measuring end-systolic elastance from information obtained outside the ventricle and thereby simplify its transduction. DESIGN: Prospective, within-animal comparative analysis. SETTING: University-based laboratory study. PARTICIPANTS: Six mixed-breed dogs. INTERVENTIONS: Instrumentation included minor axis sonomicrometry, ascending aortic flow probe, aortic and ventricular pressure transducers, and constricting cuffs on the vena cavae and aorta. MEASUREMENTS AND MAIN RESULTS: Elastance was determined from the equation PES = EES (VED - VES), where VED - VES is stroke volume and PES is end-systolic arterial pressure. EES was derived from both preload and afterload manipulation. Cardiac performance indices were calculated automatically by computer under conditions of varying load and inotropy. This extraventricular method of elastance calculation was compared by linear regression and analysis of variance to preload recruitable stroke work, traditional EES determination (using ventricular dimension instead of volume), and LVdP/dt at 50 mmHg. EES measured from the aortic sites correlated well with the other contractility indicators (p < 0.003 in all cases) and demonstrated more sensitivity and stability under loading manipulation than traditional EES. A strong relationship between the change in stroke volume and end-systolic ventricular diameter during acute aortic constriction (r = 0.924, p < 0.0001) was observed, and the mean r value for the individual outflow elastance measurements was 0.97 +/- 0.02. CONCLUSIONS: In this study, measurement of EES from the ventricular outflow tract during progressive aortic constriction produced results more consistent and descriptive than EES by traditional techniques and has the potential for obtaining elastance measurements from possibly less invasive techniques.

Analysis of Variance↗
PubMed1995

The Kell blood group system.

The Kell blood group system is complex containing over 20 different antigens. Some of the Kell antigens may be organized in 5 sets of paired alleles with opposing high and low incidence antigens while others are independently expressed. Molecular cloning established that Kell antigens are carried on a 93kDa, type II, membrane glycoprotein. The Kell gene (KEL) is located at 7q 32-36 and spans about 21,5 kb. The coding sequence is organized in 19 exons. The promoter region does not contain TATA sequences but has possible transcription binding sites for GATA-1 and Sp1. Kell protein shares a putative enzymatic active amino acid sequence with a large family of zinc endopeptidases and has closest structural and sequence homology with neutral endopeptidase 24,11 (a.k.a. enkephalinase, CALLA) and endothelin converting enzyme (ECE-1). The molecular basis of several important Kell antigens has been determined and all are due to base substitutions causing single amino acid changes. The K1/K2 polymorphism is due to a C to T substitution in exon 6, encoding a threonine to methionine change. This mutation disrupts an N-glycosylation site. Two PCR-based methods, including use of allele-specific primers, have been developed which may be used to determine fetal K1/K2 genotypes. These tests can potentially identify those pregnancies at risk for hemolytic disease of the newborn. The allelic relationship of Kpa, Kpb and Kpc was confirmed, since single base substitutions in the same codon encode 3 different amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1995

Molecular basis of the K:6,-7 [Js(a+b-)] phenotype in the Kell blood group system.

BACKGROUND: The Kell blood group system consists of at least 21 antigens. KEL6(Jsa) is a low-incidence antigen that has an antithetical relationship with the high-incidence KEL7(Jsb) antigen. The molecular basis of KEL6 that appears in less than 1.0 percent of the general population, but in up to 19.5 percent of African Americans, was unknown. STUDY DESIGN AND METHODS: Nineteen exons of the Kell gene (KEL) were amplified by polymerase chain reaction (PCR) assays of genomic DNA obtained from individuals with K:6,-7 [Js(a+b-)] phenotype. The PCR products were sequenced. A comparison was made of the sequence of the PCR products and the sequence of K:-6,7, the common phenotype. RESULTS: KEL from individuals with the K:6,-7 phenotype had two base substitutions in exon 17. One was a missense mutation (T-to-C base substitution) at nucleotide (nt) 1910, which predicts an amino acid change from leucine to proline; the other was a silent substitution (A-to-C) at nt 2019. The T-to-C substitution eliminated a restriction site for Mnl I, whereas the A-to-G substitution eliminated a Dde I site. Analyses of exon 17 in seven unrelated persons with K:6,-7 phenotype by Mnl I and Dde I enzymes showed the expected presence of restriction fragment length polymorphisms. CONCLUSION: The base substitutions T-to-C at nt 1910 and A-to-G at nt 2019 are unique to KEL6. The predicted Leu-->Pro change may disrupt the alpha-helical structure and thus form the epitope for KEL6.

Alleles↗
PubMed1995

Conformational energies of substrates and inhibitors for carboxypeptidase A: stereoelectronic effect.

Because of the complexity involved in binding of a ligand to an enzyme the conformational preference of the bound ligand has not been well understood yet. We have examined the conformational energies of ligands for carboxypeptidase A using ab initio calculations. Considering the large stereoelectronic effect of 4-5 kcal/mol, the energetic preference of the unbound ligand conformers which arises from the stereoelectronic effect appears to play a significant role in determining the bound ligand conformations.

3-Mercaptopropionic Acid↗
PubMed1995

Interaction of the fragments characteristic of bactenecin 7 with phospholipid bilayers and their antimicrobial activity.

Bactenecin 7 (Bac7), a cationic polypeptide from large granules of bovine neutrophils, exhibits antimicrobial activity mainly against Gram-negative bacteria. This peptide is characterized by high contents of Arg and Pro and by a unique sequence with an Arg-clustered region and three tandem repeats. In order to investigate the structure-function relationship of Bac7, two peptide fragments, which correspond to residues 1-17 (RRIRPRPPRLPRPRPRP, an Arg-clustered region) and 46-59 (LPFPRPGPRPIPRP, one of three tandem repeats), respectively, were synthesized. Circular dichroism (CD) measurements of the two fragments indicated that they took particular conformations, although these were not defined. These peptides can bind to acidic phospholipid bilayers without marked conformational changes. When acidic phospholipid bilayers entrapping 5,6-carboxyfluorescein were treated with the peptides, no trace of the dye leaked out, indicating that the peptides lack the ability to disrupt lipid membranes. Fragment 1-17 showed weak antimicrobial activity against several bacteria, but fragment 46-59 was almost inactive. The present results suggest that longer fragments or the entire molecule of Bac7 may be required for full expression of antimicrobial activity and that Bac7 may manifest its activity by a bacteriostatic rather than a bacteriolytic mechanism.

Amino Acid Sequence↗
PubMed1995

Enhancement of immunostimulatory activity by dual substitution of C8-substituted guanine ribonucleosides: correlation with increased cytokine secretion.

Guanine ribonucleosides with single substitutions at the C8 position (monosubstituted) or with dual substitutions at the C8 and N7 positions (disubstituted) up-regulate a spectrum of immunologic responses, including cytolytic responses to tumor cells. The current studies were undertaken to determine the effects of dual substitution on a number of nucleoside-inducible immunological parameters. To do so, two monosubstituted analogues, 8-bromoguanosine and 8-mercaptoguanosine, were directly compared with two disubstituted analogues, 7-methyl-8-oxoguanosine and 7-allyl-8-oxoguanosine (loxoribine). All of the compounds enhance natural killer (NK) activity, lymphocyte proliferation, and antibody production in dose-dependent fashion. However, the potency and maximal activity of the disubstituted analogues are considerably greater than those of the monosubstituted analogues. Spleen cells stimulated for 48 h with the disubstituted compounds produce immunoreactive interleukin (IL) 1 alpha, IL-6, tumor necrosis factor-alpha (TNF alpha), and interferon-gamma (IFN gamma). Monosubstituted analogues induce lower quantities of IL-6, TNF alpha, and IFN gamma and fail to induce detectable levels of IL-1 alpha. Total IFN activity, assessed by viral inhibition assay, is also lower for the monosubstituted analogues. Augmentation of antibody secretion by B cells is diminished for neither mono- nor disubstituted compounds upon incubation with anti-cytokine antibodies. In contrast, anti-IFN alpha beta markedly reduces the effects of monosubstituted analogues on NK activity but has less marked effects on NK induction by the disubstituted compounds. A similar pattern of differences is seen for lymphocyte proliferation. Thus, although the analogues induce synthesis of several cytokines, to date only IFN alpha beta appears directly involved in enhancement of NK activity and lymphocyte proliferation. The present data do not, however, exclude the existence of an autocrine stimulatory mechanism not susceptible to inhibition by anti-cytokine antibodies.

Adjuvants, Immunologic↗
PubMed1995

The tomato Never-ripe locus regulates ethylene-inducible gene expression and is linked to a homolog of the Arabidopsis ETR1 gene.

Fruit ripening represents a complex system of genetic and hormonal regulation of eukaryotic development unique to plants. We are using tomato ripening mutants as tools to elucidate genetic components of ripening regulation and have recently demonstrated that the Never-ripe (Nr) mutant is insensitive to the plant growth regulator ethylene (M.B. Lanahan, H.-C. Yen, J.J. Giovannoni, H.J. Klee [1994] Plant Cell 6:521-530). We report here ethylene sensitivity over a range of concentrations in normal and Nr tomato seedlings and show that the Nr mutant retains residual sensitivity to as little as 1 part per million of ethylene. Analysis of ripening-related gene expression in normal and mutant ethylene-treated fruit demonstrates that Nr exerts its influence on development at least in part at the level of ethylene-inducible gene expression. We have additionally used cloned tomato and Arabidopsis sequences known to influence ethylene perception as restriction fragment length polymorphism probes, and have identified a tomato locus linked to Nr that hybridizes to the Arabidopsis ETR1 gene at low stringency, suggesting the possibility that Nr may be homologous to ETR1.

Arabidopsis↗
PubMed1995

Prognosis and clinical relevance of recurrent oral ulceration in Behçet's disease.

There is no way of predicting whether a patient with recurrent oral ulcerations (ROU) will develop Behçet's disease (BD). In the absence of a valid laboratory test to exclude BD, such oral ulcerations result in a diagnostic problem when they occur as the sole and earliest manifestation of disease. We assessed the prognosis of ROU by performing prospective evaluations of 67 patients who had only a history of ROU and were registered at the Behçet's Disease Specialty Clinic at Severance Hospital of Yonsei University, Seoul, Korea. Thirty-five patients (52.2%) developed overt manifestations of BD at an average of 7.7 years after the onset of ROU. The frequency of recurrence was 9.8 times per year in progressive cases. From these results, it appears that highly recurrent ROU is a warning signal for BD. Careful examinations of patients, including their minor symptoms, additional laboratory tests, and regular follow-ups by physicians are required for proper diagnosis.

Adolescent↗
PubMed1995

Locus-specific amplification of HLA class I genes from genomic DNA: locus-specific sequences in the first and third introns of HLA-A, -B, and -C alleles.

We have identified locus-specific sequences in the first and third introns flanking the polymorphic second and third exons of HLA class I genes. PCR primers derived from these conserved sequences produced DNA fragments of the expected sizes for each of the HLA-A, -B, and -C loci in the amplification of genomic DNA. PCR products generated using each of the locus-specific sets of primers displayed exquisite locus specificity, as assessed by hybridization with oligonucleotide probes specific for ten classical and non-classical HLA class I genes. Amplification with these primer sets was effective and specific for the HLA alleles tested under the given PCR conditions. When hybridized with oligonucleotides derived from shared polymorphic sequence motifs, reaction patterns of PCR products from each locus were precisely as expected from published or database sequences. Chemiluminescent signals generated from digoxygenin-ddUTP-labeled probes were even for all samples and as strong as those obtained in MHC class II typing. These locus-specific primer sets derived from intron sequences provide an effective means to amplify genomic DNA which will facilitate PCR-based HLA class I typing methods. This will also allow HLA class I typing to be conducted with greater precision, at lower cost, and faster than previously described class I typing methodologies.

Alleles↗
PubMed1995

Drastic reduction in antimicrobial activity by replacement of Orn residues with Lys in cyclized amphiphilic beta-structural model peptides.

Recent investigation have indicated that cyclic dodeca- and tetradecapeptides, cyclo(-Leu-Orn-Leu-Orn-D-Phe-Pro)2 (Orn-DLL-12) and cyclo(-Leu-Orn-Leu-Orn-Leu-D-Phe-Pro)2 (Orn-DLL-14), which are designed on the basis of a cyclic beta-structural antibiotic, gramicidin S (GS), inhibit the growth of Gram-positive and -negative bacteria with high potency [Ando, S., Nishikawa, H., Takiguchi, H., Lee, S. & Sugihara, G. (1993) Biochim. Biophys. Acta 1147, 42-49]. In this study we designed and synthesized two analogs, Lys-DLL-12 and Lys-DLL-14, in which four Orn residues in Orn-DLL-12 and Orn-DLL-14 were replaced by Lys residues, respectively, and investigated their interactions with model membranes in terms of CD and dye-leakage experiments, antimicrobial activity and lytic activity for human erythrocytes. Both peptides newly designed showed no antimicrobial activity and no lytic activity of erythrocytes. The present CD study showed that the presence of neutral liposomes and of acidic liposomes of natural or synthetic phospholipids results in no remarkable conformational difference between Orn-DLL-12/-14. The leakage experiment showed a clear relation between the antimicrobial activity and the leakage ability in acidic synthetic phospholipid liposomes but no correlation in acidic natural ones. The difference in hydrophobic and hydrophilic balance between Orn-DLL-12/14 and Lys-DLL-12/14 (derived from the increasing hydrophobicity due to an increase of four methylene units by the substitution of Lys for Orn) may be one of the important factors in the drastic decrease in activity.

Amino Acid Sequence↗
PubMed1995

Acute generalized exanthematous pustulosis.

A case of acute generalized exanthematous pustulosis (AGEP) is described. A brief review of AGEP is undertaken with emphasis on its differentiation from acute generalized pustular psoriasis. AGEP is also compared with and contrasted to acute febrile neutrophilic dermatosis, or 'Sweet's syndrome' and Sneddon-Wilkinson pustular dermatosis.

Adrenal Cortex Hormones↗
PubMed1995

Altered ACTH and corticosterone responses to interleukin-1 beta in male rats exposed to an alcohol diet: possible role of vasopressin and testosterone.

We have previously shown that female rats exposed to an alcohol (ethanol, E) diet exhibited a blunted ACTH response to systemically administered interleukin-1 beta (IL-1 beta). Because of the presence of gender differences in the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and of the possible role played by sex steroids in modulating the inhibitory influence of E in females, we studied the ability of a 10-day E diet to alter ACTH and corticosterone secretion of intact or castrated male rats injected with IL-1 beta or endotoxin, a releaser of endogenous cytokines. Pituitary responsiveness to secretagogues that mediate the endocrine effects of IL-1 beta, namely corticotropin-releasing factor (CRF) and vasopressin (VP), was also investigated. The ACTH responses of animals fed ad libitum (C group) or pair-fed (PF group) to the intravenous administration of IL-1 beta or endotoxin were not statistically different (p > 0.05); therefore, results from these two groups were combined in the initial experiments. Subsequent experiments only used E and C animals. When compared with this latter group, intact E males showed a significant (p < 0.01) decrease in ACTH levels measured 30 and 60 min after the intravenous injection of IL-1 beta or endotoxin. In contrast, E rats released as much corticosterone as C rats in response to IL-1 beta, but significantly (p < 0.05) more following administration of endotoxin (lipopolysaccharide). The stimulatory effect of VP on ACTH release was also measurably blunted by alcohol, whereas that of CRF was not. In none of these experiments were any significant differences observed between C and PF rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1995

Microabscesses of the liver and spleen in AIDS: detection with 5-MHz sonography.

PURPOSE: To determine whether sonograms of the liver and spleen, obtained with 5-MHz linear-array transducers, aid in detection of hepatosplenic microabscesses in patients with acquired immunodeficiency syndrome (AIDS). MATERIALS AND METHODS: Abdominal sonographic examinations (n = 111) were performed in 102 consecutive patients with AIDS. A 3.5-MHz sector transducer was used in each study, with additional images of the hepatic and splenic parenchyma obtained with a 5-MHz linear-array transducer. Each study was reviewed without benefit of the 5-MHz images, and categories of the hepatic and splenic parenchyma were as follows: 1, lesions definitely present; 2, lesions possibly present; and 3, lesions absent. The 5-MHz images were subsequently reviewed, and studies were recategorized. Findings were correlated with results of pathologic examination. RESULTS: The 5-MHz scans enabled identification of focal hepatic or splenic lesions in 14 of 96 studies placed in category 2 or 3 on the basis of the 3.5-MHz sector scans. CONCLUSION: In patients with AIDS, 5-MHz sonograms of the liver and spleen enable detection of microabscesses not confidently identified on 3.5-MHz scans.

AIDS-Related Opportunistic Infections↗
PubMed1995

Borderline personality disorder symptoms and severity of sexual abuse.

OBJECTIVE: This study explored the relationship of specific symptoms of borderline personality disorder to dimensions of severity of sexual abuse experiences in childhood. METHOD: A group of 41 patients with borderline personality disorder who retrospectively reported a childhood history of sexual abuse on the Familial Experiences Interview were studied. Six items from the Diagnostic Interview for Borderline Patients (DIB) were chosen on the basis of their univariate (chi-square) association with a sexual abuse severity scale that was developed by the authors and their research team. These six DIB items were each modeled in a logistic regression. Predictor variables were the most severe experience within each of three dimensions of sexual abuse: 1) perpetrator (sexual abuse by a parent), 2) duration (sexual abuse that was ongoing), and 3) type (sexual abuse that involved penetration). RESULTS: The severity dimension that was most frequently found to be a significant predictor of the sum of the six DIB items as well as the total scaled DIB score was the duration dimension. Ongoing sexual abuse predicted parasuicidal behavior as well. CONCLUSIONS: Ongoing sexual abuse may be a strong determinant of specific aspects of the disordered interpersonal behavior and functioning found in patients with borderline personality disorder. The expectation that the world is an empty, malevolent place may have some of its roots in the repetition of sexual abuse experiences in childhood. This expectation of malevolence among patients with borderline personality disorder may manifest itself in psychotherapy through regressive and distancing behavior.

Adolescent↗
PubMed1995

A somatic cell genetic method for identification of untargeted mutations in the glucocorticoid receptor that cause hormone binding deficiencies.

Mouse T lymphoma cell line W7MG1, which is killed by physiological concentrations of glucocorticoid agonists, was used as a convenient genetic system for isolating sublines containing mutant glucocorticoid receptors (GR) with hormone-binding deficiencies. Partially hormone-resistant cell clones were derived from chemically mutagenized cell populations by selecting for growth in moderate concentrations of dexamethasone (Dex) and then screening for failure to grow in high Dex concentrations. Such clones are likely to have mutant GR. In GR cDNA clones from the partially resistant cell sublines, three different functionally significant mutations in the hormone-binding domain were identified: Leu-569 changed to Phe (L569F), Leu-670 to Phe (L670F), and Met-672 to Ile (M672I). Dose-response analyses with Dex and affinity labeling studies with dexamethasone 21-mesylate in transiently transfected cells indicated that all three mutant GR species had hormone-binding deficiencies. However, at saturating Dex concentrations the mutant and wild type GR activated a hormone-inducible reporter gene to the same extent; thus, these three mutations did not affect the ability of GR to activate transcription of the reporter gene after hormone was bound. In dose-response curves conducted with several glucocorticoid agonists, mutations L670F and M672I caused no change in ligand-binding specificities, while mutation L569F caused a modest change in specificity. Quantitative hormone-binding studies conducted with mutant GR synthesized in cell-free reactions showed that mutant GR species L569F and M672I had reduced Dex-binding affinities both at 0 C and at 22 C in the presence of molybdate. In contrast, for the L670F mutant, which exhibited the severest deficiency in vivo, the hormone-binding deficiency in the cell-free system was evident only at 26-37 C and primarily in the absence of molybdate. We propose that the L670F GR is an activation-labile type of mutant, which binds hormone normally in the presence of heat shock protein 90 but loses hormone rapidly after dissociation from heat shock protein 90. These three mutations define two new subregions of the GR polypeptide that are important for hormone binding.

Amino Acid Sequence↗
PubMed1995

Comparison of thallium-201 and gallium-67 citrate scintigraphy in the diagnosis of pulmonary disease.

Gallium is presently used in the diagnosis of inflammatory, granulomatous, and neoplastic lung disease despite its many logistical problems. In contrast, thallium-201 scintigraphy, which was initially developed for myocardial imaging, offers the principal advantage of immediate imaging and diagnosis although it had not been investigated previously for use in pulmonary disease. In this study, thallium and gallium were prospectively compared with each other for the diagnosis of a variety of lung diseases. The overall concordance rate was 75%. Thallium was found to be significantly more sensitive than gallium for the entire group studied (N = 51, p < 0.006). In a subset of patients in whom a firm diagnosis was established, thallium was also found to be more sensitive, 86% vs 64%. The greater sensitivity of thallium-201 and its several inherent advantages suggest that thallium-201 should replace gallium-67 citrate as the radioisotope of choice for nuclear imaging of the chest.

Adolescent↗