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Biomedical subjects

S H Chou

Publications and source records attributed to S H Chou.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sheared purine x purine pairing in biology.

The Watson-Crick G x C and A x T base-paired DNA duplex has been the single most important milestone in modem molecular biology. However, it is possible that other types of stable DNA structures besides the double helix might exist, since only about 5% of the human chromosome is transcribed and expressed. Stable, four-stranded G-tetraplex DNA structures occur in the extensive tandem repeated sequences at the telomeres of chromosome. Formation of stable triplexes of the Py x Pu x Py or Pu x Pu x Py type have been implicated at the control regions of certain human genes. We review and discuss the various types of DNA duplex structures containing stable sheared base-pairs and compare their structural characteristics with that of B-DNA. Pu x Pu structural motifs are found in the highly conserved sequences at the replication origins of several single-stranded DNA viruses and in the peri-centromeric regions of human chromosomes, and may be involved in important biological functions, such as viral DNA replication and centromere formation.

Base Sequence↗
PubMed1997

Evidence for the involvement of catecholamines in the 2-DG-induced immunomodulatory effects in spleen.

The role of catecholamines in immune changes associated with the metabolic stress of 2-deoxy-D-glucose (2-DG) was examined in this study. Male Lewis rats were pretreated with the nonselective beta-adrenergic receptor antagonist nadolol (0-0.5 mg/kg) and then received either a saline or 2-DG (500 mg/kg) injection. Nadolol attenuated the 2-DG-induced suppression of splenic T-cell mitogenic response and interferon-gamma production and increased nitric oxide production by macrophages in a dose-dependent manner. Conversely, nadolol did not attenuate the 2-DG-induced changes in immune parameters in peripheral blood leukocytes. These results suggest that the peripheral release of catecholamines is responsible for 2-DG-induced splenic immune alterations, whereas the peripheral release of catecholamine is not responsible for 2-DG-induced blood immune alterations. Furthermore, the neuroendocrine mechanisms responsible for splenic immune changes induced by the metabolic stress of 2-DG administration were the same as those involved in immune changes induced by physical and psychological stress. Thus, this study suggests that common neuroendocrine pathways exist for several types of stress-induced immunomodulations.

Adjuvants, Immunologic↗
PubMed1996

Hairpin loops consisting of single adenine residues closed by sheared A.A and G.G pairs formed by the DNA triplets AAA and GAG: solution structure of the d(GTACAAAGTAC) hairpin.

The DNA undecamers GTACAAAGTAC (AAA 11-mer) and GTACGAGGTAC (GAG 11-mer) have been studied in solution by high-resolution NMR spectroscopy. Both duplexes form stable hairpins containing single deoxyadenosine loops and stems containing five base-pairs that are closed at the loop end by sheared AxA and GxC pairs, respectively. These molecules thus contain new AAA and GAG loop turn motifs. All protons, including the chiral H5'/H5" protons of the loop residues, were assigned using NOESY, DQF-COSY and heteronuclear 1H-31P COSY experiments. The backbone torsion angles were constrained using experimental data from NOE crosspeaks, three-bond 1H-1H coupling constants and four-bond 1H-31P coupling constants and four-bond 1H-31P coupling constants. The AAA and GAG 11-mers form similar structures in solution. The detailed structure of the AAA 11-mer was determined by the combined use of NMR, distance geometry and energy minimization methods. This structure exhibits good stacking of the loop adenosine base on the closing 5Ax7A sheared pair, with the 6A base stacking on the 5A base and the 6A deoxyribose stacking with the 7A base. All sugars in the AAA 11-mer hairpin adopt the typical DNA C2'-endo conformation and a sharp backbone turn occurs between residues 6A and 7A. This loop turn is brought about mainly by a change in the backbone phosphate torsion angles from zeta(g-) alpha(g-) to zeta(g+) alphat(g+) at the turn. The gamma torsion angle of residue 7A in the closing sheared pair also changes from gauche+ to trans. In Pu1NPu2 loop turns of the GCA, AAA and GAG types, the chemical shift of the H4' proton of the loop deoxyribose depends on the nature of Pu2; this reflects the stacking of the loop sugar on the Pu2 base and the different ring current effects of A or G in this position.

Adenine↗
PubMed1996

A single G-to-C change causes human centromere TGGAA repeats to fold back into hairpins.

Recently, we established that satellite III (TGGAA)n tandem repeats, which occur at the centromeres of human chromosomes, pair with themselves to form an unusual "self-complementary" antiparallel duplex containing (GGA)2 motifs in which two unpaired guanines from opposite strands intercalate between sheared G.A base pairs. In separate studies, we have also established that the GCA triplet does not form bimolecular (GCA)2 motifs but instead promotes the formation of hairpins containing a GCA-turn motif in which the loop contains a single cytidine closed by a sheared G.A pair. Since TGCAA is the most frequent variant of TGGAA found in satellite III repeats, we reasoned that the potential of this variant to form GCA-turn miniloop fold-back structures might be an important factor in modulating the local structure in natural (TGGAA)n repeats. We report here the NMR-derived solution structure of the heptadecadeoxynucleotide (G)TGGAATGCAATGGAA(C) in which a central TGCAA pentamer is flanked by two TGGAA pentamers. This 17-mer forms a rather unusual and very stable hairpin structure containing eight base pairs in the stem, only four of which are Watson-Crick pairs, and a loop consisting of a single cytidine residue. The stem contains a (GGA)2 motif with intercalative 14G/4G stacking between two sheared G.A base pairs; the loop end of the stem consists of a sheared 8G.10A closing pair with the cytosine base of the 9C loop stacked on 8G. The remarkable stability of this unusual hairpin structure (Tm = 63 degrees C) suggests that it probably plays an important role in modulating the folding of satellite III (TGGAA)n repeats at the centromere.

Centromere↗
PubMed1996

On the relative ability of centromeric GNA triplets to form hairpins versus self-paired duplexes.

While tandem repeats of the human centromere DNA pentamer sequence TGRAA form stable "self-complementary" [TGRAATGRAA]2 duplexes (R = G or A) containing the GA-bracketed unpaired purine stack motif, their phase-shifted variants NAATGNAATG (N = A, G, C, T) were found to exist in solution as an equilibrium mixture of a duplex containing the GA-bracketed unpaired stack motif and a hairpin containing a single-residue loop closed by a sheared G x A pair. The stability of the hairpin form relative to duplex form of GNA triplets was found to be GCA>GAA/GTA>>GGA, with the CAATGCAATG sequence mostly in the hairpin form and the GAATGGAATG sequence mostly in the [GAATGGAATG]2 duplex form. The chemical shifts of the H1' and H4' protons of the central N residue in GNA triplets were found to differ markedly in the duplex and hairpin forms and are diagnostic indicators of which conformation the oligonucleotide adopts. Comparison between the structures of the G x A-closed C loop motif and the G x A-bracketed unpaired G-stack [GGA]2 motif reveals remarkably similar stacking by the loop C residue and the intercalated G residue on the adjacent sheared G x A pair. The anomalous upfield chemical shifts of the H1' and H4' protons in [GGA]2 motifs and the H4' proton in GCA loops, and the different sugar conformations in these two motifs, can be explained by interstrand versus intrastrand stacking of the central (G or C) deoxyribose with the adenine base. Based on these studies, a DNA sequence GTGGAATGGAATGGAAC was designed and shown to form a duplex containing three [GGA]2 motifs, while its 9G-->9C analog GTGGAATGCAATGGAAC was found to adopt a stable hairpin containing a (GGA)2 motif in the stem and a G x A-closed single C-loop.

Base Sequence↗
PubMed1996

Characterization of the effect of 2-deoxy-D-glucose(2-DG) on the immune system.

This study was designed to characterize the effects of the metabolic stress of administration of 2-deoxy-d-glucose (2-DG, 500 mg/kg) on immune function. Male Lewis rats were exposed to one or five injections (one every 48 h) of 2-DG. Control rats received saline injections. Administration of 2-DG induced a reduction of total leukocytes in the spleen, thymus, and blood. The reduction was most prominent in animals that received five injections of 2-DG. The ratio of CD4(+)/CD8(+) in the spleen was decreased due to a significant increase of CD8(+) T-cell subpopulation. Additionally, 2-DG induced a suppression of mitogenic responsiveness and IFN-gamma production in both whole blood and spleen lymphocytes. The production of IL-1 and IL-2 was significantly reduced in the blood, but not in the spleen. Conversely, there was a significant increase in nitric oxide production in cultures of Con A-, PHA-, and LPS-stimulated splenocytes from 2-DG-injected animals compared with saline-injected controls. In blood cultures stimulated with Con A and PHA, the nitric oxide production of the group that received five injections of 2-DG was significantly higher than in the group that received one injection of 2-DG or saline. These results demonstrated that the metabolic stress 2-DG induced a downregulation of Th 1 cellular immune function in a manner similar to physical and psychological stressors. Additionally, the use of 2-DG in rats provided an important model with which to study metabolic stress.

Animals↗
PubMed1995

The structure of a novel DNA duplex formed by human centromere d(TGGAA) repeats with possible implications for chromosome attachment during mitosis.

The solution structure of the DNA duplex [GTGGAATGGAAC]2 containing a tandem repeat of the human centromere (TGGAA)n unit has been determined by two-dimensional nuclear magnetic resonance (2D-NMR), distance geometry (DG) and molecular dynamics/energy minimization (MD/EM) methods. This remarkably stable "self-complementary" antiparallel duplex contains a tandem repeated motif in which unpaired guanine residues from opposite strands intercalate and costack between sheared G.A pairs. Twelve independent refined structures were determined from the NMR data and found to converge to a single family of closely related structures with pair-wise r.m.s.d. values of 0.55 +/- 0.25 Angstrum. All sugar residues are in the normal C2'-endo conformation except for the unpaired guanosines, which are in the unusual C3'-endo conformation. The guanosine residues of the bracketing G.A pairs have high-antiglycosidic torsion angles and zeta backbone torsion angles close to the trans domain. The structure exhibits many unusual interstrand interactions, including base-sugar stacking, base-phosphate hydrogen bonding and cross-strand base stacking. The [GGA]2 unit contains a stack of four contiguous guanine residues, all of which have their hydrogen-bonding surface (N2H-N1H-O6-N7) exposed to solvent and available for interaction with other bases or ligands. This unexpected property may explain the unique morphology and function of the human centromere in mitosis.

Base Sequence↗
PubMed1995

Conformation of the propeptide domain of factor IX.

The propeptide domain in the precursor forms of blood clotting proteins contains the recognition sequences for gamma-carboxylase. In hemophilia B, several point mutations in this propeptide domain are responsible for the inherited disease. A peptide containing the propeptide sequence of factor IX was synthesized by solid phase methods. Two dimensional 1H-NMR and CD studies indicate that this peptide motif adopts an alpha-helical structure in a 40% trifluoroethanol-containing aqueous solution. The results suggest that the amphipathic alpha-helix within the propeptide domain of factor IX could create a recognition surface for gamma-carboxylase. The influences of mutations and their relationship with the alpha-helical structure are discussed.

1-Carboxyglutamic Acid↗
PubMed1995

Structure of a single-cytidine hairpin loop formed by the DNA triplet GCA.

In certain contexts the DNA triplet GGA, when juxtaposed on opposite strands of a DNA duplex, shows the unusual property of pairing with itself in an antiparallel orientation to form the (GGA)2 motif. In this motif the central guanines do not pair but intercalate and stack between sheared G.A pairs. Similar studies with GCA triplets reveal that they do not form analogous paired (GCA)2 motifs but instead strongly promote formation of a hairpin, the structure of which is now reported here. The GCA hairpin loop consists of a single cytidine residue closed by a sheared G.A pair and this structure is discussed in the context of triplet expansions in triplet-repeat diseases.

Base Sequence↗
PubMed1995

Histopathologic studies of gastric mucosa following gastric substitution in benign and malignant esophageal disease.

Gastric interposition was performed and prospectively studied in 9 patients with esophageal cancer, 1 patient with esophageal neurofibroma and 5 with corrosive esophageal stricture. The postoperative follow-up periods were between 6 to 68 months with a mean of 28.6 months. The subjects were then endoscopically reviewed. Twelve of them were macroscopically normal. The others exhibited signs of inflammation and hyperemia. Mucosal biopsies were obtained at the upper and lower third of the graft. The histologic findings were compared with those of the preoperative specimens. Among the 15 post-operative specimens, only minute histologic changes were seen. Three patients whose proximal grafts showed inflammatory signs revealed congestion. Another 2 patients exhibited granulocyte infiltration in the mucosa of the distal third. The mucosal structure of the remaining 10 patients was similar to that of the preoperative graft. In conclusion, the macroscopic and microscopic changes were few and minimal although there were alterations in function, physiology and location of the stomach.

Adult↗
PubMed1994

The unusual structure of the human centromere (GGA)2 motif. Unpaired guanosine residues stacked between sheared G.A pairs.

The centromere of human chromosomes contains multiple repeats of the DNA sequence d(TGGAA)n. This sequence has the interesting property of pairing with itself to form stable duplexes. We have determined the solution structure of the unusual DNA duplex 5'-TGGAATGGAA:TGGAATGGAA-3' at atomic resolution. The duplex contains unpaired staggered guanosine residues, which co-stack by intercalation between sheared G.A and A.G base-pairs to form an interesting new structural motif, the GA-bracketed G-stack. The TGGAA repeat unit contains six "steps", four of which are not Watson-Crick base-pairs.

Adenosine↗
PubMed1994

DNA sequence GCGAATGAGC containing the human centromere core sequence GAAT forms a self-complementary duplex with sheared G.A pairs in solution.

The DNA sequence dGCGAATGAGC has a well-resolved, two-dimensional nuclear Overhauser (NOESY) spectrum that is suitable for high quality solution structure determination by NMR methods; in solution this sequence forms a stable self-complementary duplex containing sheared G.A base-pairs. A total of 220 distance constraints derived from time-dependent NOE measurements were collected and refined by repeated back-calculation of the NOESY spectra. Distance information from imino proton studies and from exclusive two-dimensional correlated spectroscopy (E. COSY) and/or linewidth analysis was included in the structure calculation using the program DSPACE 4.2, followed by restrained energy minimization with the program DISCOVER using the AMBER force field. The energies of the distance geometry (DG) structures decreased rapidly in the first few cycles and approached -510 +/- 3 kcal after 1000 cycles of conjugate gradient minimization (about 540 kcal lower than in the initial DG structures). All 15 final DG structures converged to a single family of closely related structures with pair-wise r.m.s.d. values of 0.96 +/- 0.34 A, which was further reduced by energy minimization to 0.70 +/- 0.35 A. Rather unusual structural features of the duplex are revealed in the final structures. The results indicate that, in addition to normal sequences with standard base-pairing, unusual nucleic acid structures can also be determined in solution with quite high precision by NMR/distance geometry methods.

Base Composition↗
PubMed1994

Use of glutaraldehyde solution in the treatment of acute aortic dissections.

We report on a promising method for toughening and strengthening the fragile aortic wall that involves the direct application of a 25% glutaraldehyde solution and that has proved to be both technically simple and safe. The operation was successfully employed in 5 patients with acute aortic dissections, 3 with a Stanford type A and 2 with a type B dissection. Histologic examination of the glutaraldehyde-treated portions of the aortic wall showed no detectable difference between them and the sections of untreated aortic wall. All patients survived the operation. The duration of follow-up ranged from 9 to 31 months (mean, 14.0 months). All 5 patients were in good condition at the time of the last follow-up. The preliminary results indicate that the use of a 25% glutaraldehyde solution to strengthen the aortic wall during operations for the repair of acute aortic dissections, regardless of whether they are type A or type B, may reduce the incidence of catastrophic perioperative bleeding and promote favorable results.

Acute Disease↗
PubMed1994

Imaging diagnosis of cavernous hemangioma of the rib--one case report and review of the literature.

Osseous hemangioma is a benign neoplasm, rarely located in the ribs. A 56-year-old female patient without specific complaint had a large extrapleural lesion on chest posteroanterior radiograph. Expansile destruction of left seventh rib and relatively fine trabeculation were noticed in the mass from plain roentgenogram and computed tomography (CT). Contrast enhancement in noncalcified component of the lesion was revealed. Pleural effusion, lung parenchymal or mediastinal abnormality were not identified. Resection of the lesion with part of the originating rib was carried out. The pathologic diagnosis was cavernous hemangioma. We present a case with a large rib hemangioma which often leads to difficulty in radiologically differential diagnosis with other common malignant rib tumors. We also review the literature about hemangioma and malignant neoplasms of the ribs.

Bone Neoplasms↗
PubMed1994

[Variations in ATPase activities of erythrocytic membrane and endocytic ionic levels in cases with pregnancy induced hypertension].

The ATPase activities of erythrocytic membrane and endocytic ionic concentration were determined in 30 cases with pregnancy induced hypertension (PIH), 25 normal pregnancies and 20 non-pregnant controls. The activities of Na(+)-K(+)-ATPase and Ca(++)-ATPase were found significantly lower in PIH than those in the controls, but Mg(++)-ATPase activity revealed no Na+ and Ca++ values were significantly higher while Mg++ obviously lower in those with PIH than in the controls, and K+ was almost the same in the three groups. These findings suggested a close relationship between the pathogenesis of PIH and the abnormal ATPase activities and ionic levels.

Adult↗
PubMed1993

Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth.

Hepsin was previously identified as a putative cell-surface serine protease. When hepatoma cells were treated with anti-hepsin antibodies, their growth was substantially arrested, suggesting the requirement of hepsin molecules present at the cell surface for normal cell growth. This was further supported by a gross inhibition of cell growth with hepsin-specific antisense oligonucleotides. Upon treatment of cells with antisense oligonucleotides, rapid reduction in cellular hepsin was observed. This reduction in cellular hepsin levels was accompanied by drastic morphological changes. Various tissues in the developing mouse embryo showed greatly elevated hepsin levels in regions of active proliferation. These results indicate that hepsin plays an essential role in cell growth and maintenance of cell morphology.

Animals↗
PubMed1993

Thoracic endoscopic T2-T3 sympathectomy in palmar hyperhidrosis: experience of 112 cases.

Palmar hyperhidrosis is a troublesome and embarrassing disorder that causes professional, psychological, and social handicaps. Its etiology is unknown, although surgical treatment by thoracic sympathectomy is presently believed to be the best method of cure. Up to now, numerous methods of sympathectomy, including open thoracotomy, as well as posterior and supraclavicular approaches have been described. We favor endoscopy at this time due to both its simplicity and its resultant short hospital stay. During the period between March 1988 and October 1990, 112 patients (55 males, 57 females) suffering from palmar hyperhidrosis underwent 222 thoracoscopic T2-T3 sympathectomies under general anesthesia in our department. The remaining 2 hands had a second operation of unilateral open thoracotomy due to pleural adhesion. The patients' ages ranged from 15 to 45 years. A total of 220 hands became dry while the others showed improvements. There were 5 patients who required unilateral chest tube insertion, 2 for post-thoracotomy drainage and 3 for intrathoracic hemorrhage after thoracoscopic pneumonolysis. The average operative time (bilateral) was 30.8 min and hospital stay was 2.87 days. Compensatory hyperhidrosis was the major complication. There was no mortality. We therefore consider thoracoscopic sympathectomy to be a simple, safe, and effective method for treating palmar hyperhidrosis.

Adolescent↗