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Biomedical subjects

S Cho

Publications and source records attributed to S Cho.

At least 145 records · Page 8Linked to original sources

Evaluation of the major metabolites of raloxifene as modulators of tissue selectivity.

Raloxifene (LY139481 HCl) is a selective estrogen receptor modulator (SERM) which blocks the effects of estrogen on some tissues, such as the breast and uterus, while mimicking estrogen in other tissues, such as bone. To study the origins of this unique pharmacology, we have prepared the major metabolites of raloxifene as chemical probes for examining the estrogen receptor function in vitro and in vivo. In human breast cancer cell (MCF-7) related assays, these glucuronide conjugates show little affinity for the estrogen receptor and are more than two orders of magnitude less potent at inhibiting cell proliferation than raloxifene. In non-traditional estrogen target tissue, such as bone, these metabolites are less effective than the parent at inhibiting cytokine-stimulated bone resorbing activity in rat osteoclasts or producing transforming growth factor beta-3 (TGF-beta3). In animal models, tissue distribution studies with radiolabelled metabolite indicate that conversion to raloxifene occurs readily in a variety of tissues including the liver, lung, spleen, kidney, bone and uterus. Differential conversion of metabolite in target organs, such as bone and the uterus, is not observed indicating that the origin of raloxifene's pharmacology does not result from tissue-selective deconjugation of metabolite to parent.

Adenocarcinoma↗

Low molecular weight storage material in infantile ceroid lipofuscinosis (CLN1).

The identification of the genetic defect in CLN1 as a palmitoyl-protein thioesterase deficiency initiated a search for the lysosomal storage material. Pulse-chase labelling of fibroblasts and lymphoblastoid cell lines with [35S]cysteine revealed the presence of lipid [35S]cysteine material in CLN1 fibroblasts and not in controls, CLN2 or CLN3 patients or other patients with lipidosis. A single band comigrated with the acylcysteine standard and labelling with [3H]palmitate showed a band of material which eluted from the silicic acid column with the phospholipid fraction and which co-migrated with the lipid-[35S]cysteine band. The storage material is tentatively identified as palmitoylcysteine.

Adolescent↗

A new multivalent B cell activation model--anti-IgD bound to Fc gamma RI: properties and comparison with CD40L-mediated activation.

CHO cells permanently transfected with mouse Fc gamma RI alpha chain were prepared and used as a model to polyclonally activate murine B cells. The transfected CHO cells were treated with mitomycin C and placed into culture with varying quantities of anti-IgD. Using this model, murine splenic B cells (from BALB/c or C57Bl/6) were activated by mouse IgG2a-anti-IgD (10.4.22 or AF3.33) in a manner that is analogous to the activation of B cells seen with highly polyvalent anti-IgD (H delta(a)/1) prepared by chemical cross-linking to dextran. Efficient B cell activation was seen with nanogram quantities of anti-IgD. In the presence of IL-4 and IL-5, IgG1 production levels were equivalent to or better than seen when stimulation was with H delta(a)/1-dextran; however, IgE induction was not seen in either situation. The Ig production capacity was compared to that seen when B cells were activated with CD40L, using either CD40L-transfected CHO or a soluble CD40L construct. In the presence of IL-4 and IL-5, once a critical threshold of B cells was present, IgE and to a lesser extent IgG1 production was inversely proportional to B cell number when CD40L was the activating agent. In contrast, with Fc gamma RI-anti-IgD, IgM and IgG1 production was directly proportional to B cell number, while IgE production was never seen. Finally, when B cells were co-activated with immobilized anti-IgD and CD40L simultaneously, the IgE production from B cells induced by CD40L was strongly inhibited, while IgG1 and IgM production were not affected. Since B cell co-activation via sIg and CD40L would be a common scenario in secondary follicles, this inhibition of IgE production may be one of the reasons why serum IgE levels are much below IgG in normal immune situations.

Animals↗

Phylogenetic utility of elongation factor-1 alpha in noctuoidea (Insecta: Lepidoptera): the limits of synonymous substitution.

To test its phylogenetic utility, nucleotide sequence variation in a 1,240-bp fragment of the elongation factor-1 alpha (EF-1 alpha) gene was examined in 49 moth species representing the major groups of the superfamily Noctuoidea. Both parsimony and distance analyses supported the monophyly of nearly all groups for which there are clear morphological synapomorphies. Clades of subfamily rank and lower, probably mid-Tertiary and younger, were strongly supported. The third codon position contains 88% of variable sites, and approaches saturation at approximately 20% sequence divergence, possibly due to among-site rate heterogeneity and composition bias; higher divergences occur only in association with shifts in composition. Surprisingly, the few nonsynonymous changes appear no more phylogenetically reliable than synonymous changes. Signal strength for basal divergences is weak and fails to improve with character weighting; thus, dense taxon sampling is probably needed for strong inference from EF-1 alpha regarding deeper splits in Noctuoidea (probably early Tertiary). EF-1 alpha synonymous changes show promise for phylogeny reconstruction within Noctuidae and other groups of Tertiary age.

Animals↗

A new nuclear gene for insect phylogenetics: dopa decarboxylase is informative of relationships within Heliothinae (Lepidoptera: Noctuidae).

The lack of a readily accessible roster of nuclear genes informative at various taxonomic levels is a bottleneck for molecular systematics. In this report, we describe the first phylogenetic application of the sequence that encodes the enzyme dopa decarboxylase (DDC). For 14 test species within the noctuid moth subfamily Heliothinae that represent the previously best-supported groupings, a 690-bp fragment of DDC resolved relationships that are largely concordant with prior evidence from elongation factor-1 alpha (EF-1 alpha), morphology, and allozymes. Although both synonymous and nonsynonymous changes occur in DDC substantially more rapidly than they do in EF-1 alpha, DDC divergences within Heliothinae are below saturation at all codon positions. Analysis of DDC and EF-1 alpha in combination resulted in increased bootstrap support for several groupings. As a first estimate of previously unresolved relationships, DDC sequences were analyzed from 16 additional heliothines, for a total of 30 heliothine species plus outgroups. Previous relationships based on DDC were generally stable with increased taxon sampling, although a two- to eightfold downweighting of codon position 3 was required for complete concordance with the 14-species result. The weighted strict consensus trees were largely resolved and were congruent with most although not all previous hypotheses based on either morphology or EF-1 alpha. The proposed phylogeny suggests that the major agricultural pest heliothines belong to a single clade, characterized by polyphagy and associated life history traits, within this largely host-specific moth subfamily. DDC holds much promise for phylogenetic analysis of Tertiary-age animal groups.

Animals↗

Lichen planus pigmentosus presenting in zosteriform pattern.

Lichen planus pigmentosus (LPP) has thus far been described as a condition of unknown etiology which clinically differs from the classical lichen planus (LP) by exhibiting dark brown macules and/or papules mostly in exposed areas and flexural folds and a longer clinical course without pruritus or scalp, nail or mucosal involvement. Histopathologically, LPP shows the typical changes seen in LP, but with thinning of epidermis. We report a case of LPP that developed in a unilateral, zosteriform pattern on the left flank of a 49-year-old man. This case seems to lie in the middle of the spectrum between classical LP and ashy dermatosis, and, to the best of our knowledge, is the first report of LPP presenting in the zosteriform pattern.

Humans↗

Perinatal outcomes in a prospective matched pair study of pregnancy and unexplained elevated or low AFP screening.

Unexplained elevated or low maternal serum alpha-fetoprotein (MSAFP) is reported to indicate adverse perinatal outcome. We designed a prospective matched pair study to gain additional information about the type and frequency of adverse neonatal or maternal outcomes. Subjects were selected from 16,445 women who received second trimester MSAFP screening during the 4.5 year study period. For each unexplained elevated or low subject, a control patient in the second trimester of pregnancy was chosen by matching eight individual traits. After follow-up, 356 pairs were identified, for the unexplained low MSAFP group and 139 pairs for the unexplained elevated MSAFP group. Outcome information was obtained by way of a physician questionnaire. For the unexplained low MSAFP group, complications occurred no more often than for the paired controls and these pregnancies may not be considered at high risk for adverse outcome. Our study supports a strong association between unexplained elevated MSAFP and adverse neonatal outcomes of low birth weight, fetal death, preterm delivery, and fetal growth retardation. The highest frequency of adverse neonatal outcome occurred when the multiple of median value was > or = 4.0. Our study does not support an association between elevated MSAFP and maternal complications of hypertensive disorder, oligohydramnios, or placental abruption.

Birth Weight↗

[Photomicrographs of a pleural biopsy specimen, showing malignant mesothelioma and necrosis--malignant pleural mesothelioma in a patient with sarcoidosis].

A 45-year-old woman was admitted to Nara Medical University Hospital because of right-sided chest pain. Both a chest X-ray film and a chest CT scan revealed bilateral hilar and mediastinal lymphadenopathy and right pleurisy. She underwent fiberoptic bronchoscopy and mediastinoscopy. Biopsy specimens of the lung and mediastinal lymph nodes showed non-caseous epithelioid cell granulomas. After on ophthalmologic examination, she was given a diagnosis of sarcoidosis with a pleural lesion and uveal involvement. The pleurisy become less severe and the lymph nodes shrank without any treatment. About one year later, she complained of right-sided chest pain again and a chest X-ray film revealed diffuse thickening of the pleural on the right side. Examination of pleural biopsy specimens revealed malignant mesothelioma. We know of no previous report from Japan of malignant pleural mesothelioma in a patient with sarcoidosis.

Biopsy↗

Loss of heterozygosity at chromosome segment Xq25-26.1 in advanced human ovarian carcinomas.

To determine whether a tumor suppressor gene of importance to epithelial ovarian cancer resides on the X chromosome, we examined loss of heterozygosity (LOH) in 123 epithelial ovarian cancer cases. In 54 such cases, we examined LOH at 26 loci on the human X chromosome. In eight cases, we examined LOH in 14 loci and in 61 cases we examined LOH in 13 loci. Matched DNA samples from tumors and corresponding normal tissues were analyzed by polymerase chain reaction (PCR) amplification of microsatellite markers. Frequent losses were found in epithelial carcinomas at the Xq25-26.l region, including DXS1206 (34.5% loss in informative cases), DXS1047 (27.7%), HPRT (24.1%), and DXS1062 (33.3%). The minimum overlapping region of LOH was approximately 5 megabases (Mb), flanked by DXS1206 (Xq25) and HPRT (Xq26.1). The methylation status of the remaining allele of the androgen receptor gene in the tumors exhibiting LOH at the Xq25-26.1 region suggested that the loss was exclusively in the inactive X chromosome. We next determined whether a significant relationship exists between Xq LOH and other parameters, including histologic grade and/or clinical stage of the tumors and LOH at TP53. The Xq LOH had a significant association with grade 2 to 3 tumors at stages II to IV. Sixteen of 18 cases that showed Xq LOH revealed LOH at the TP53 locus, and 45% of tumors exhibiting LOH at TP53 showed Xq LOH. These results suggest that there may be a tumor suppressor gene or genes which escape inactivation of the X chromosome at Xq25-26.1, and that the loss of the gene(s) at Xq25-26.1 is frequently accompanied by loss of the TP53 or loss of another gene on chromosome 17. These losses may contribute to the progression from a well-differentiated to a more poorly differentiated state or to metastatic aggressiveness.

Carcinoma↗

[A correlation between atrial natriuretic peptide, brain natriuretic peptide, and perioperative cardiac and renal functions in open heart surgery].

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are homeostatic hormones secreted from the human heart which protect both cardiac and the renal function. It is well known that these hormones increase in patients along with increases in the severity of congestive heart failure or acute myocardial infarction. However, as yet there are no reports in the literature on changes of the secreted level of ANP or BNP in surgical patients undergoing cardiopulmonary bypass (CPB). We evaluated the relationship between ANP, BNP, and perioperative cardiac and renal functions in patients with heart failure caused by CPB. We selected 45 patients of elective open heart surgery. We measured plasma level of ANP in all 45 cases, and BNP in 18 cases at preoperation, postoperation, and postoperatively three days after, respectively. At the same time, the cardiac index (CI) was measured. These cases were divided into the following groups. Group A1 (n = 23): cases in which the preoperative ANP was less than 40 pg/ ml. Group A2 (n = 22): cases in which the preoperative ANP was more than 40. Group B1 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as mach as the normal level. Group B2 (n = 8): cases in which the preoperative BNP is increased to the level of 5 times as much as the normal level. Group B2 (n = 10): cases in which the preoperative BNP was more than that of 10 times as mach as normal level. We then carried out a comparative study of the perioperative cardiac and renal functions in group A1 and A2, and group B1 and B2, respectively. In the terms of preoperative cardiac and renal function, there were no significant differences between groups A1 and A2, and there were no significant differences in urinary volume during CPB or post operative CI. However, the urinary volume during CPB of group B1 was significantly more than that of B2. Furthermore, the incidence of postoperative CI in group B1. Furthermore, the incidence of postoperative CI in group B1 was significantly higher than in B2. The preoperative and post operative third day BNP level had significant negative correlations with postoperative CI and postoperative third day CI, respectively (r = -0.641, -0.514, p = 0.008, 0.012). The postoperative ANP and BNP levels tend to a mean level roughly similar to one another because of the easing of cardiac stress by surgery and postoperative management. According to these results and several instances in the literature, a preoperative high BNP is considered to suggest a potential perioperative risk for cardiac and renal function. We conclude that determination of the plasma BNP level can be helpful for decisions related to CPB flow and measures taken to enhance cardiac and renal protection during surgery, and therefore is a useful reference for perioperative management.

Aged↗

Evolution of early TIMI 2 flow after thrombolysis for acute myocardial infarction. GUSTO-1 Angiographic Investigators.

BACKGROUND: Patients with early Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow after thrombolysis appear to have outcomes similar to thrombolytic failures. To evaluate the origin and evolution of early TIMI 2 flow, we examined early and late angiographic and ventriculographic data from the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO-1) angiographic study. METHODS AND RESULTS: Of the 914 patients with both 90-minute and 5- to 7-day catheterizations, 278 patients had TIMI grade 2 flow at 90 minutes. At follow-up, 188 (67%) had improved to TIMI grade 3 flow. At 90 minutes, patients with TIMI grade 2 flow had greater infarct vessel narrowing and a significantly greater incidence of thrombus than patients with TIMI grade 3 flow. At the 5- to 7-day follow-up, patients whose flow had improved from TIMI grade 2 at 90 minutes to grade 3 flow at follow-up had larger-caliber vessels (minimum luminal diameter, 0.99 +/- 0.47 versus 0.84 +/- 0.48 mm; P = .03) and a lower incidence of visible thrombus (26% versus 38%, P = .04) than those with persistent TIMI grade 2 flow. These patients also had a higher mean ejection fraction (57.5 +/- 14.1% versus 52.8 +/- 12.9%, P = .02) and better infarct zone wall motion (-2.1 +/- 1.5 versus -2.6 +/- 1.3 SD per chord, P = .01) at the 5- to 7-day follow-up. Patients in whom flow improved from TIMI grade 2 at 90 minutes to TIMI grade 3 by 5 to 7 days had significantly better left ventricular function than patients with persistent TIMI grade 0, 1, or 2 flow and constituted a group whose left ventricular function was intermediate between those who had no reperfusion (TIMI grades 0 and 1) and those whose reperfusion was complete (TIMI grade 3). CONCLUSIONS: These data suggest that incomplete clot lysis plays a significant role in the pathogenesis of TIMI grade 2 flow. Furthermore, early TIMI grade 2 flow may be sufficient to provide prolonged myocyte viability, which will further recover if flow normalizes.

Aged↗

Modulation of tyrosine hydroxylase and aromatic L-amino acid decarboxylase after inhibiting monoamine oxidase-A.

After acute administration of the monoamine oxidase inhibitor clorgyline there is a reduction of aromatic L-amino acid decarboxylase and tyrosine hydroxylase activity in the mouse striatum. Similar responses were seen after administering the non-selective monoamine oxidase inhibitor pargyline and high, but not low, doses of the selective monoamine oxidase-B inhibitor deprenyl. Changes of tyrosine hydroxylase activity were observed only when subsaturated concentrations of the pteridine cofactor were used for the assay. The monoamine oxidase inhibitors altered the abundance of aromatic L-amino acid decarboxylase and tyrosine hydroxylase mRNA in the midbrain. Pargyline and high doses of deprenyl increased, aromatic L-amino acid decarboxylase mRNA, while clorgyline initially decreased and then increased it. All three compounds caused an early decrease of tyrosine hydroxylase mRNA. The acidic metabolites of dopamine appeared most affected by pargyline and clorgyline, supporting the notion that deamination of striatal dopamine in rodents is primarily by monoamine oxidase-A. Our results suggest, that striatal tyrosine hydroxylase and aromatic L-amino acid decarboxylase are apparently modulated via different mechanisms in response to perturbation of dopamine metabolism.

Animals↗

Reduced sympathetic innervation after alteration of target cell neurotransmitter phenotype in transgenic mice.

Neurotransmitters play a variety of important roles during nervous system development. In the present study, we hypothesized that neurotransmitter phenotype of both projecting and target cells is an important factor for the final synaptic linkage and its specificity. To test this hypothesis, we used transgenic techniques to convert serotonin/melatonin-producing cells of the pineal gland into cells that also produce dopamine and investigated the innervation of the phenotypically altered target cells. This phenotypic alteration markedly reduced the noradrenergic innervation originating from the superior cervical ganglia. Although the mechanism by which the reduction occurs is presently unknown, quantitative enzyme-linked immunoassay showed the presence of the equivalent amounts of nerve growth factor (NGF) in the control and transgenic pineal glands, suggesting that it occurred in a NGF-independent manner. The results suggest that target neurotransmitter phenotype influences the formation of afferent connections during development.

Animals↗

Purification and physical properties of the male and female double sex proteins of Drosophila.

The double sex gene (dsx) encodes two proteins, DSX(M) and DSX(F), that regulate sex-specific transcription in Drosophila. These proteins bind target sites in DNA from which the male-specific DSX(M) represses and the female-specific DSX(F) activates transcription of yolk protein (Yp) genes. We investigated the physical properties of these DSX proteins, which are identical in their amino-terminal 397 residues but are entirely different in their carboxyl-terminal sequences (DSX(F), 30 amino acids; DSX(M), 152 amino acids). DSX(M) and DSX(F) were overexpressed in cultured insect cells and purified to near homogeneity. Gel filtration chromatography and glycerol gradient sedimentation showed that at low concentrations both proteins are dimers of highly asymmetrical shape. The axial ratios are approximately 18:1 (DSX(M), 860 X 48 angstroms; DSX(F), 735 X 43 angstroms). At higher concentrations, the proteins form tetramers. Through use of a novel, double crosslinking assay (protein-DNA plus protein-protein), we demonstrated that a DNA regulatory site binds to both monomers of the DSX dimer and to only two monomers of the tetramer. Furthermore, binding another DNA molecule to what we presume is the second and identical site in the tetramer dramatically shifts the equilibrium from tetramers to dimers. These oligomerization and DNA binding properties are indistinguishable between the male and female proteins.

Animals↗

Effects of sevoflurane with and without nitrous oxide on human cerebral circulation. Transcranial Doppler study.

BACKGROUND: This study was designed to evaluate the effects of sevoflurane with and without nitrous oxide on human middle cerebral artery (MCA) flow velocity, cerebrovascular carbon dioxide reactivity, and autoregulation compared with the awake state using transcranial Doppler ultrasonography. METHODS: In 14 patients, the time-mean middle cerebral artery flow velocity (Vmca) was measured when the end-tidal carbon dioxide level was approximately 30, 40, and 50 mmHg under the following conditions: (1) awake; (2) with 2% (1.2 MAC) sevoflurane; and (3) with 1.2 MAC sevoflurane-60% nitrous oxide. In six other patients, the cerebrovascular autoregulation during anesthesia was determined using intravenous phenylephrine to increase blood pressure. RESULTS: Sevoflurane (1.2 MAC) significantly decreased Vmca compared with the awake value at each level of end-tidal carbon dioxide, whereas 1.2 MAC sevoflurane-60% nitrous oxide did not exert significant influence. The Vmca in normocapnic patients decreased from 69 cm/s to 55 cm/s with 1.2 MAC sevoflurane and then increased to 70 cm/s when nitrous oxide was added. Sevoflurane (1.2 MAC) with and without 60% nitrous oxide had a negligible effect on cerebrovascular carbon dioxide reactivity. A phenylephrine-induced increase of mean arterial pressure did not influence Vmca during anesthesia. CONCLUSIONS: Sevoflurane (1.2 MAC) reduced Vmca compared with the awake condition, whereas the addition of nitrous oxide caused Vmca to increase toward the values obtained in the awake condition. The cerebrovascular carbon dioxide reactivity and autoregulation were well maintained during 1.2 MAC sevoflurane with and without 60% nitrous oxide.

Adult↗