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Biomedical subjects

S Park

Publications and source records attributed to S Park.

At least 289 records · Page 16Linked to original sources

Expression of retinoic acid receptor-beta sensitizes prostate cancer cells to growth inhibition mediated by combinations of retinoids and a 19-nor hexafluoride vitamin D3 analog.

Retinoids and analogs of vitamin D3 may achieve greater in vivo applications if the toxic side effects encountered at pharmacologically active doses could be alleviated. These seco-steroid hormones often act in concert, and therefore, we attempted to dissect these interactions by isolating combinations of receptor-selective retinoids and a potent vitamin D3 analog [1alpha,25(OH)2-16ene-23-yne-26,27,F6-19nor-D3, code name LH] that were potent inhibitors of prostate cancer cell growth at low, physiologically safer doses. Using a panel of prostate cancer cell lines representing progressively more transformed phenotypes, we found that the LNCaP cell line (least transformed) was either additively or synergistically inhibited in its clonal growth by LH and various naturally occurring and receptor-selective retinoids, the most potent combination being with a retinoic acid receptor (RAR)betagamma-selective retinoid (SR11262). The effect was not found with either PC-3 (intermediate transformation) or DU-145 (most transformed). We also undertook RT-PCR to examine the subtypes of RARs present, and we found that PC-3 and DU-145 did not express RARbeta. Stable expression of RARbeta into the RARbeta-negative PC-3 cells resulted in increased sensitivity to SR11262 and LH proportional to the amount of RARbeta expressed. This study indicates that RARbeta may play an important role in synergistically controlling cell proliferation, and expression is lost with increased prostate cancer cell transformation. Simultaneous administration of a potent vitamin D3 analog and receptor-selective retinoids may have therapeutic potential for the treatment of androgen-dependent and -independent prostate cancer.

Apoptosis↗

Coronary bypass grafting for single-vessel coronary artery disease: a 17-year review with short- and long-term follow-up.

STUDY OBJECTIVES: We reviewed our short- (30 days) and long-term (up to 17 years) experience with surgical revascularization for patients with angiographically documented isolated single-vessel coronary artery disease. DESIGN: Retrospective study of single-vessel coronary artery bypass procedures performed from January 1980 through June 1996. During this time, 100 consecutive patients underwent a single-vessel coronary artery bypass. All patients were men with a mean age of 59+/-9 years (range, 35 to 78 years) and a mean ejection fraction of 56+/-8% (range, 35 to 77%). The vessels bypassed included the left anterior descending in 66 (66%), right coronary artery in 31 (31%), and the obtuse marginal in 3 (3%). RESULTS: Short-term results reveal no deaths and six (6.0%) complications. Long-term follow-up by chart review and telephone survey was available in 87 (87%) patients at a mean of 46.9 months (range, 12 to 151 months). Cumulative freedom from angina and repeated revascularization was 93% and 98% at 1 year and 55% and 81% at 10 years, respectively (Kaplan-Meier). CONCLUSION: Single-vessel coronary artery bypass for isolated single-vessel disease can be performed with minimal morbidity and no mortality and provides excellent long-term relief of angina.

Adult↗

Transcription of the rat p53 gene is mediated by factor binding to two recognition motifs of NF1-like protein.

In this study we analyzed the ratp53 promoter by electrophoretic mobility shift assay (EMSA) and DNase I footprinting analysis. As a result we identified two protein binding elements (element 1: -296 to -312, element 2: -195 to -219) with sequence homology to each other. The two identified elements bind to the same kind of protein. To identify the protein binding to these elements, competition assays were carried out with double stranded oligonucleotides containing NF1, YY1, and CRE consensus motifs. Only the NF1 consensus motif competed with element 1 and 2. Element 2 is conserved between the rat, human, and mouse p53 promoters, and has an NF1 consensus motif. However, the sequences of element 1 are comparatively variable between the species. Only the element 1 region of the rat p53 promoter has partial homology to the NF1 consensus motif. This suggests that the element 1 is specific for the rat p53 gene. The molecular mass of the binding protein, determined by Southwestern blotting analysis, was 40 kDa, which is different from that of NF1. In EMSA with an anti-NF1 antibody, DNA-protein complexes were neither supershifted nor decreased. The 40 kDa protein was also detected in rat spleen and lung, but not in kidney. The binding protein was purified by sequence-specific DNA affinity chromatography and it was confirmed that the purified protein binds to the two regions. It was also proved that the identified two elements are required for basal level transcription of the rat p53 gene by in vitro transcription assay.

Animals↗

Effects of the pH-controlled hemoglobin vesicles by CO2 gas.

The hemoglobin vesicle (HbV) is a red cell substitute encapsulating purified concentrated Hb in a phospholipid vesicle. In order to improve the oxygen carrying capability of HbV, the pH value of the Hb solution should be adjusted to 7.0 in the HbV preparation, and then the pH value should be adjusted to 7.4 where HbV functions as an oxygen carrier, because the maximum value of [Hb]/[Lipid] was obtained in which the pH of the Hb solution was 7.0, and the metHb formation rate was suppressed in the pH 7.4. Generally, the pH control of the inner aqueous phase of HbV is difficult by changing the pH in the outer phase. We could control the pH of the Hb solution from 7.4 to 7.0 by dissolving CO2 into the Hb solution, and after the preparation of HbV, the pH of HbV is changed to 7.4 by reducing the pressure. The resulting pH-controlled HbV by CO2 gas showed a high [Hb]/[Lipid] value of 1.7 with a low rate of metHb formation.

Arylsulfonates↗

Frontoorbital advancement by gradual distraction. Technical note.

A substantial number of patients with coronal synostosis who undergo frontoorbital advancement still require additional surgical treatment to correct increased intracranial pressure or unsatisfactory craniofacial structure. However, frontoorbital advancement currently requires elevation of the frontal as well as the orbital bone, which can result in a fragile dura mater and partial resorption of the advanced bone. Thus the dura is easily torn by dissection and the advanced bone is further resorbed and deformed during repeated craniofacial operations. To avoid these drawbacks and to create an easier second surgical treatment via the intracranial approach, a new technique for frontoorbital advancement is presented. In this technique frontoorbital bone is advanced as a single unit, without elevation from the underlying dura, by means of gradual distraction. The details of the technique and an illustrative case are reported.

Cranial Sutures↗

Desmoplastic cerebral astrocytoma of infancy: a case report.

We present a case of desmoplastic cerebral astrocytoma of infancy (DCAI) in a 9-month-old boy including immunohistochemical and proliferative activity studies. It was mainly composed of glial fibrillary acidic protein (GFAP)-positive astrocytes and desmoplastic stroma. Studies with Ki-67 and synthetic phase fraction disclosed a low proliferative activity. Flow cytometric study revealed diploidy pattern. These findings suggest a positive correlation with the favorable prognosis.

Astrocytoma↗

Cytokine secretion patterns of T cells responding to haptenized-human serum albumin in toluene diisocyanate (TDI)-induced asthma patients.

Our understanding immune response mechanisms to chemical allergens has been limited. It was partly due to the nature of antigens, recognized by T cells, not being well characterized. In the present study, we examined a hypothesis that a reactive chemical allergen, toluene diisocyanate (TDI), react with autologous proteins, thereby inducing T cell responses to the modified self protein in vivo. TDI-human serum albumin (HSA) conjugates were prepared and the presence of antigenic epitopes on the TDI-HSA conjugate was confirmed by IgE ELISA. We examined proliferative and cytokine production responses in TDI-induced asthma patients using the TDI-HSA conjugate as an antigen. Although proliferative responses of peripheral blood mononuclear cells (PBMCs) were not detected, production of IFN-gamma was observed in both PBMC and T cell lines obtained from some newly-diagnosed patients by ELISA. Mitogen-inducible IL-4 production was also detected in some T cell lines. Results of this study may have two implications. One is that presentation of haptenized-self protein to the immune system may induce activation of T cells. The other is that T cells responding to this modified self protein may play a role in the pathogenesis of the chemical allergen-induced asthma by producing cytokines such as IFN-gamma and possibly IL-4.

Allergens↗

Factors affecting transformation efficiency of BCG with a Mycobacterium-Escherichia coli shuttle vector pYUB18 by electroporation.

BCG has been one of the vehicles for multi-recombinant vaccine. However, low transformation efficiency of BCG with plasmid DNA hampered studies involving expression of foreign antigens in BCG. In an effort to determine the optimal conditions, this study was initiated to investigate factors involved in the transformation of BCG with a Mycobacterium-Escherichia coli shuttle vector, pYUB18, by electroporation. Mycobacterium bovis BCG (strain 1173P2) was grown in Middlebrook (M) 7H9 broth containing albumin-dextrose-catalase and 0.05% tween 80, and transformed BCG was grown in M7H10 agar containing kanamycin for counting viable cells. Pretreatment of BCG with 10 mM CaCl2 improved the transformation efficiency, but overnight incubation of BCG with 1% glycine did not. The transformation efficiency in BCG also varied depending on voltage, resistance, and DNA concentration. The maximum transformation efficiency was obtained when the infinity resistance, 12.5 Kv/cm, and 100 ng of DNA were used, and reached 1.4 x 10(5) CFU/microgram of plasmid DNA, which is about 3-100 times greater than those from previous reports. The transformation conditions described in this study, therefore, will give us a better position for employing BCG as a vehicle for developing multi-recombinant vaccines.

Calcium Chloride↗

A sensate liner for biomedical monitoring applications.

This program develops and demonstrates technologies useful for implementing a manageable cost effective systems approach to monitoring the medical condition of personnel by way of an instrumented uniform hereafter referred to as a Sensate Liner (SL). The SL consists of a form fitting garment which contains and interconnects sensing elements and devices to an electronics pack containing a processor and transmitter. The SL prototype requires fiber, textile, garment and sensor development. The SL textile consists of a mesh of electrically and optically conductive fibers integrated into the normal structure (woven or knitted) of fibers and yarns selected for comfort and durability. A suite of SL garment compatible embedded biological and physical sensors are then integrated into the SL. The initial SL sensor suite is selected to improve triage for combat casualties. Additional SL sensor concepts for medical monitoring will be discussed.

Clothing↗

Immune response of sows vaccinated with attenuated transmissible gastroenteritis virus (TGEV) and recombinant TGEV spike protein vaccines and protection of their suckling pigs against virulent TGEV challenge exposure.

OBJECTIVE: To compare recombinant transmissible gastroenteritis virus (TGEV) spike protein, (SP) R2-2, with attenuated live virus (ALV) vaccine in sows during late pregnancy. ANIMALS: 13 TGEV-seronegative sows and their pigs. PROCEDURE: At prepartum weeks (PPW) 6 and 4, sows of groups 1 and 2 received ALV via the oral/intranasal (O/IN) route. At PPW 2, group-1 sows received ALV IM and group-2 sows received SPR2-2 IM. Group-3 sows received SPR2-2 IM at PPW 4 and ALV O/IN at PPW 2. Sows of group 4 (negative controls) were inoculated O/IN with mock-infected ST cell fluids at PPW 6 and 4 and IM with Sf9 cell lysates at PPW2 (n = 2), or IM with Sf9 cell lysates at PPW4 and O/IN with mock-infected ST cell fluids at PPW2 (2). Serum, colostrum, and milk samples were tested for antibody to TGEV, and a lymphoproliferative (LP) assay was done on blood mononuclear cells. Suckling pigs were challenge exposed with virulent TGEV. RESULTS: Sows of groups 1 and 2 had higher IgG and significantly higher antibody titers in colostrum; their pigs had significantly higher serum antibody titer. At challenge exposure of their pigs, LP responses of group-2 sows were significantly higher than those of sows in the other 3 groups. Mean pig mortality ranged from 43 (group 2) to 92% (group 4). Significant negative correlations were observed among litter mortality and sow LP response, colostral titer, and pig serum titer at time of challenge exposure. CONCLUSIONS: In sows vaccinated twice with attenuated live TGEV, the recombinant SPR2-2 administered IM may be comparable to ALV administered IM as a booster. Vaccination failed to provide complete protection to suckling pigs after challenge exposure.

Animals↗

Randomized trial of daily versus three-times-weekly prophylactic ganciclovir after lung and heart-lung transplantation.

BACKGROUND: Cytomegalovirus is an important cause of morbidity and mortality risk after lung transplantation. Ganciclovir, when given for a period of up to 3 months after lung transplantation, has been shown to reduce the incidence and severity of cytomegalovirus. However, daily prophylaxis is associated with considerable expense, inconvenience, and morbidity risk. The goal of this study was to determine whether 3-times-weekly dosage is as effective as daily prophylaxis with ganciclovir in preventing cytomegalovirus disease. METHODS: Seventy-two consecutive subjects who had either donor or recipient cytomegalovirus seropositivity were randomized to the daily group (n = 35) or the 3-times-weekly group (n = 37). All subjects received twice-daily ganciclovir treatment for 2 weeks. Thereafter, subjects received either daily or 3-times-weekly ganciclovir dosing until 90 days after transplantation. Subjects were then monitored for 28 +/- 13 months to identify outcomes and complications. RESULTS: There were no significant differences between the daily and 3-times-weekly groups with respect to survival free from cytomegalovirus infection or survival free from cytomegalovirus disease. In both groups, cytomegalovirus infection and disease frequently emerged after the termination of prophylaxis. However, in most cases the cytomegalovirus syndromes observed were mild and in many cases could be treated on an outpatient basis. There was no significant difference between the groups in the incidence of obliterative bronchiolitis or time to onset of grade 2 bronchiolitis obliterans syndrome. Overall patient survival was better in the daily group, but the survival advantage did not appear to be related to a reduction in cytomegalovirus-related disease. Complications of ganciclovir prophylaxis included leukopenia in 2 subjects in the 3-times-weekly group and catheter-related sepsis in 6 subjects from each group. CONCLUSIONS: We conclude that intravenous ganciclovir given 3 times weekly for 3 months after transplantation is as effective as daily ganciclovir given for a similar time period. The 3-times-weekly dosing regimen did not result in increased infection, disease, or sequelae of cytomegalovirus infection when compared with the daily regimen.

Antiviral Agents↗

Organizing a functional junctional complex requires specific domains of the Drosophila MAGUK Discs large.

Discs large (Dlg) was the first identified member of an increasingly important class of proteins called membrane-associated guanylate kinase homologs (MAGUKs), which are often concentrated at cell junctions and contain distinct peptide domains named PDZ1-3, SH3, HOOK, and GUK. Dlg is localized at and required for the formation of both septate junctions in epithelial cells and synaptic junctions in neurons. In the absence of Dlg, epithelia lose their organization and overgrow. We tested the functions of each domain of Dlg in vivo by constructing transgenic flies expressing altered forms of the protein. In the first set of experiments each domain was examined for its ability to correctly target an epitope-tagged Dlg to pre-existing septate junctions. Based on these results the Hook domain is necessary for localization of the protein to the cell membrane and the PDZ2 is required for restricting the protein to the septate junction. In the second set of experiments each domain was tested for its role in growth regulation and organization of epithelial structure. These results show that PDZ1 and GUK are apparently dispensable for function, PDZ2 and PDZ3 are required for growth regulation but not for epithelial structure, and SH3 and HOOK are essential for both aspects of function. The results demonstrate the functional modularity of Dlg and clarify the functions of individual MAGUK domains in regulating the structure and growth of epithelial tissue.

Animals↗

Cloning and characterization of the 5' flanking region of human ATP-citrate lyase gene.

Two phage clones, lambda hgACL21 and lambda hgACL28, harboring the 5' flanking region of human ATP-citrate lyase (ACL) gene were identified by screening about 1.5 X 10(6) recombinant plaques from the lambdaEMBL3-human placental genomic DNA library. The 5' flanking region of ACL had the CAAT box on -92 bp from the transcription initiation site (+1), however, the TATA box was not found. The primer extension and rapid amplification of cDNA end showed that mRNA is transcribed at a thymine extending 12 bp upstream of the reported cDNA end. The sequences of 5' flanking region in 1.5 kb size of human ACL showed 60% homology with those of rat; however, no homology was found in the exon 1 and intron 1 region. Several consensus sequences, including four Sp1 binding sites, were found in the 5' flanking region of this gene. The promoter activity was assayed by transfecting the 3' or 5' deletion clones of ACL-chloramphenicol acetyl transferase (CAT) plasmid into PLC/PRF5 cells. The clone that contains the part of the first intron sequences from -659 to +440 bp showed the highest CAT activity in the transient transfection assay. High promoter activities were maintained until the transcription initiation site was removed. It is suggested that the sequences from -213 to +12 which contain three Sp1-binding sequences, CAAT box, and the transcription initiation site were necessary as a mean of for exerting the basal promoter activity of ACL gene.

ATP Citrate (pro-S)-Lyase↗

Olfactory identification deficit in relation to schizotypy.

Past studies have shown that schizophrenic men tend to be impaired on the olfactory identification task. We examined individual differences in the olfactory function in relation to schizotypy. Healthy individuals who might carry latent liability for schizophrenia participated in olfactory identification and acuity tasks. Psychometrically ascertained schizotypic men showed deficits on the olfactory identification task but not on the olfactory acuity task. The olfactory identification function partly depended on the menstrual cycle in women. But further systematic research is needed to clarify the possible role of estrogen.

Adult↗

Working memory and the syndromes of schizotypal personality.

The aim of this study was to investigate dorsolateral prefrontal function, as assessed by a spatial working memory task, in relation to the syndromal features of schizotypal personality. We found a weak association between a self-report measure of schizotypy and the working memory performance. Those with a high score on the schizotypal personality questionnaire tended to make more errors on the spatial working memory task. One sub-scale of the schizotypal personality questionnaire that taps into social functioning was significantly correlated with working memory deficit. This result suggests the presence of subtle prefrontal deficit in a sub-group of psychometrically ascertained schizotypic individuals and renders support for the past reports of working memory deficit in schizophrenia and schizotypy.

Adult↗

Voltammetric detection for capillary electrophoresis.

Several approaches to implementing amperometric detection for capillary electrophoresis have been reported. This report describes the development of a voltammetric detector for CE. The detector is designed to minimize distortion of the voltammetry due to ohmic potential drop. This was accomplished by using a cast Nafion detection cell at the end of the separation capillary. The cast Nafion detection cell provided a low-dead-volume, low-resistance cell that minimized ohmic potential drop and peak band broadening. The ability to detect the current due to oxidation of analytes superimposed on a large background current was also improved. A dynamic background subtraction scheme was used in which a second working electrode, positioned in the electrochemical cell but outside of the detection cell, was used to compensate for the background current in real time. The output of the compensating working electrode was subtracted from the output of the detecting working electrode prior to analog-to-digital conversion. Postexperimental digital background subtraction was also implemented. This approach provided optimal elimination of the background current with maximal detection of the analytical signal. The voltammetric detector developed produced high-quality voltammetric response of analytes with injected concentrations as low as 0.20 microM. The system was evaluated by obtaining CE voltammograms of a mixture of eight test phenolic acids.

Electrodes↗

Interhemispheric modulation of sensory transmission in the primary somatosensory cortex of rats.

Single unit responses of the primary somatosensory (SI) cortical neurons to the stimulation of the forepaw single digit were monitored in anesthetized rats before and after subcutaneous injection of lidocaine to an ipsilateral homologous receptive field (IHRF). Quantitative determination of the temporal changes of afferent sensory transmission was done by analyzing poststimulus time histograms of unit responses. Temporary deafferentation to the IHRF induced immediate, but reversible suppression of afferent sensory transmission in the SI cortex and this suppression lasts up to 35 min post-deafferentation period (during 10-15 min, -21.81 +/- 5.9%, P < 0.01). This result suggests that temporary absence of afferent inflow from the digit to the SI cortex may exert interhemispheric modulation of afferent sensory transmission in the opposite somatosensory cortex of anesthetized rats.

Afferent Pathways↗

Aberrant axonal projections in mice lacking EphA8 (Eek) tyrosine protein kinase receptors.

We have generated mice homozygous for a mutation that disrupts the gene encoding EphA8, a member of the Eph family of tyrosine protein kinase receptors, previously known as Eek. These mice develop to term, are fertile and do not display obvious anatomical or physiological defects. The mouse ephA8/eek gene is expressed primarily in a rostral to caudal gradient in the developing tectum. Axonal tracing experiments have revealed that in these mutant mice, axons from a subpopulation of tectal neurons located in the superficial layers of the superior colliculus do not reach targets located in the contralateral inferior colliculus. Moreover, ephA8/eek null animals display an aberrant ipsilateral axonal tract that projects to the ventral region of the cervical spinal cord. Retrograde labeling revealed that these abnormal projections originate from a small subpopulation of superior colliculus neurons that normally express the ephA8/eek gene. These results suggest that EphA8/Eek receptors play a role in axonal pathfinding during development of the mammalian nervous system.

Animals↗