Biomedical subjects

Y Ho

Publications and source records attributed to Y Ho.

At least 19 recordsLinked to original sources

PubMed2007

Different mechanisms account for extracellular-signal regulated kinase activation in distinct brain regions following global ischemia and reperfusion.

Oxidative stress after cerebral ischemia and reperfusion activates extracellular signal-regulated kinases (ERK) in brain. However, the mechanism of this activation has not been elucidated. We have previously reported that in an in vitro model of oxidative stress in immature cortical neuronal cultures, the inhibition of ERK phosphatase activity contributes to ERK1/2 activation and subsequent neuronal toxicity. This study examined whether ERK activation was associated with altered activity of ERK phosphatases in a rat cardiac arrest model. Rats in experimental groups were subjected to asphyxial cardiac arrest for 8 min and then resuscitated for 30 min. Significant ERK activation was detected in both cortex and hippocampus following ischemia/reperfusion by immunoblotting. ERK phosphatase activity was reversibly inhibited in cerebral cortex but not affected in hippocampus following ischemia/reperfusion. MEK1/2 was activated in both cerebral cortex and hippocampus following ischemia/reperfusion. Using a specific inhibitor of protein phosphatase 2A (PP2A), okadaic acid (OA), we have identified PP2A to be the major ERK phosphatase that is responsible for regulating ERK activation in ischemic brain tissues. Orthovanadate inhibited ERK phosphatase activity in brain tissues, suggesting that tyrosine phosphatases and dual specificity phosphatases may also contribute to the ERK phosphatase activity in brain tissues. Together, these data implicate ERK phosphatase in the regulation of ERK activation in distinct brain regions following global ischemia.

Animals↗

PubMed2006

Laparoscopic combined rectal anterior resection and total hysterectomy with bilateral salpingo-oophorectomy.

Pelvic conditions involving both the colorectum and gynaecological organs are traditionally treated by laparotomy. We report two cases of colorectal cancer and one of endometriosis treated by laparoscopic anterior resection and total hysterectomy bilateral salpingooophorectomy (LapAR & THBSO), at the same session. There have been no previously reported cases of the feasibility of such combined procedures, safely performed. Our results confirm that LapAR & THBSO is feasible and offers the advantages of a laparoscopic procedure in the hands of a well trained laparoscopic colorectal surgeon and gynaecologist working together.

Adult↗

PubMed2006

Observation of muon neutrino disappearance with the MINOS detectors in the NuMI neutrino beam.

This Letter reports results from the MINOS experiment based on its initial exposure to neutrinos from the Fermilab NuMI beam. The rates and energy spectra of charged current nu(mu) interactions are compared in two detectors located along the beam axis at distances of 1 and 735 km. With 1.27 x 10(20) 120 GeV protons incident on the NuMI target, 215 events with energies below 30 GeV are observed at the Far Detector, compared to an expectation of 336+/-14 events. The data are consistent with nu(mu) disappearance via oscillations with |Delta(m)2/32|=2.74 +0.44/-0.26 x10(-3)eV(2) and sin(2)(2theta(23))>0.87 (68% C.L.).

Journal Article↗

PubMed2006

Normal anatomy and common labral lesions at MR arthrography of the shoulder.

MR arthrography of the shoulder is the most accurate imaging modality in demonstrating abnormalities of the glenoid labrum and associated structures. Tears of the labrum, the capsule or the gleno-humeral ligaments can lead to pain, catching, popping or instability. The anatomy of this region is complex. We present the normal anatomy of the glenoid labrum, biceps anchor and gleno-humeral ligaments together with their normal variants and then describe common labral-ligamentous pathologies.

Cartilage, Articular↗

PubMed2004

Molecular dynamics simulations of various coronavirus main proteinases.

In this study, two homology models (denoted as MproST and MproSH) of main proteinase (Mpro) from the novel coronavirus associated with severe acute respiratory syndrome (SARS-CoV) were constructed based on the crystal structures of Mpro from transmissible gastroenteritis coronavirus (TGEV) (MproT) and human coronavirus HcoV-229E (MproH), respectively. Both MproST and MproSH exhibit similar folds as their respective template proteins. These homology models reveal three distinct functional domains as well as an intervening loop connecting domains II and III as found in both template proteins. A catalytic cleft containing the substrate binding sites S1 and S2 between domains I and II are also observed. S2 undergoes more significant structural fluctuation than S1 during the 400 ps molecular dynamics simulations because it is located at the open mouth of the catalytic cleft, while S1 is situated in the very bottom of this cleft. The thermal unfolding of these proteins begins at domain III, where the structure is least conserved among these proteins. Mpro may still maintain its proteolytic activity while it is partially unfolded. The electrostatic interaction between Arg40 and Asp186 plays an important role in maintaining the structural integrity of both S1 and S2.

Amino Acid Sequence↗

PubMed2003

Steroid sulphatase inhibitors for breast cancer therapy.

In contrast to aromatase inhibitors, which are now in clinical use, the development of steroid sulphatase (STS) inhibitors for breast cancer therapy is still at an early stage. STS regulates the formation of oestrone from oestrone sulphate (E1S) but also controls the hydrolysis of dehydroepiandrosterone sulphate (DHEA-S). DHEA can be reduced to 5-androstenediol (Adiol), a steroid with potent oestrogenic properties. The active pharmacophore for potent STS inhibitors has now been identified, i.e. a sulphamate ester group linked to an aryl ring. This has led to the development of a number of STS inhibitors, some of which are due to enter Phase I trials in the near future. Such first generation inhibitors include the tricyclic coumarin-based 667 COUMATE. Aryl sulphamates, such as 667 COUMATE, are taken up by red blood cells (rbc), binding to carbonic anhydrase II (CA II), and transit the liver without undergoing first-pass inactivation. 667 COUMATE is also a potent inhibitor of CA II activity with an IC50 of 17 nM. Second generation STS inhibitors, such as 2-methoxyoestradiol bis-sulphamate (2-MeOE2bisMATE), in addition to inhibiting STS activity, also inhibit the growth of oestrogen receptor negative (ER-) tumours in mice and are anti-angiogenic. As the active pharmacaphores for the inhibition of aromatase and STS are now known it may be possible to develop third generation inhibitors that are capable of inhibiting the activities of both enzymes. Whilst exploring the potential of such a strategy it was discovered that 667 COUMATE possessed weak aromatase inhibitory properties with an IC50 of 300 nM in JEG-3 cells. The identification of potent STS inhibitors will allow the therapeutic potential of this new class of drug to be explored in post-menopausal women with hormone-dependent breast cancer. Second generation inhibitors, such as 2-MeOE2bisMATE, which also inhibit the growth of ER- tumours should be active against a wide range of cancers.

Animals↗

PubMed2001

Effects of olfactory bulbectomy on NMDA receptor density in the rat brain:.

Olfactory bulbectomy (OBX) transects the glutamatergic efferents from the olfactory bulbs, and the changes of glutamatergic N-methyl-D-aspartate (NMDA) receptor-mediated function are though to be involved in the behavioral deficits seen in OBX rats. In the present study, irritability scores in OBX male Wistar rats were correlated with discrete regional effects on NMDA receptor function measured using a [3H] MK-801 binding assay. Irritability scores, measured before and for 2 weeks after OBX, showed a gradual increase in irritability after OBX. A reduction of the NMDA receptor density was observed in the cerebral cortex and amygdala 16 days after OBX, but not in the striatum, olfactory tubercle, entorhinal cortex, and hippocampus. These results demonstrate that OBX causes changes in the NMDA receptor system in certain brain regions and suggest that these changes may be responsible for the behavioral deficits of OBX rats.

Animals↗

PubMed2001

Structural characterization of the mouse Foxf1a gene.

Members in the superfamily of the forkhead/winged-helix transcription factors are known to play a critical role in the control of cell differentiation and tissue development. To understand the regulation and function of these genes, we have initially isolated and characterized the mouse Foxf1a gene, a novel forkhead gene predominantly expressed in the lung. The mouse gene consists of two exons with the forkhead domain contained in exon 1, and is located at band E1 on chromosome 8. Amino acid sequence of the mouse protein shares a high degree of homology to that of the corresponding human protein. The tissue specificity of expression of the mouse gene also resembles that found in the human gene. This gene is primarily expressed in the lung, and to a lesser extent in placenta and tissues in gastrointestinal tract. The transcription start site was mapped to 113 nucleotides upstream from the putative translation initiation site. The promoter of the mouse gene is highly GC rich and contains neither a CAAT nor a TATA box. A series of luciferase report constructs driven by the promoter and various deletions in the 5' flanking region of the gene were constructed and employed in transient transfection studies using a line of SV40 transformed mouse lymph node endothelial cells (SVEC4-10), which express the endogenous Foxf1a gene, and a line of mouse hepatoma cells (Hepa 1-6), in which Foxf1a is not expressed. To our surprise, these reporter genes are equally active in both cell lines. Further studies have shown that the proximal 5' flanking sequence and exon 1 of the endogenous gene are highly methylated in Hepa 1-6 cells but not in SVEC4-10 cells, suggesting that DNA methylation but not cell-specific transcription factor(s) regulates cell specificity of gene expression in these cultured cells.

Amino Acid Sequence↗

PubMed2001

Neisseria meningitidis lipopolysaccharide modulates the specific humoral immune response to neisserial porins but has no effect on porin-induced upregulation of costimulatory ligand B7-2.

The role of lipopolysaccharide (LPS) in the specific humoral response to meningococcal porins was investigated by measuring anti-PorA or -PorB antibody levels in mice immunized with wild-type meningococcal strain H44/76 or with its recently described LPS-negative mutant. Two murine strains were used for these immunizations: C3H/HeJ, which is LPS hyporesponsive, or C3H/HeOuJ, which is LPS responsive. A high level of anti-PorB immunoglobulin G (IgG) response was induced in both strains of mice immunized with either organism. The response induced by the wild-type strain was greater in C3H/HeOuJ mice than in C3H/HeJ mice, while the response induced by the LPS-negative mutant was similar in the two murine strains. Additionally, the anti-PorB response was similar in C3H/HeJ mice immunized with either bacterial strain. In general, the anti-PorA IgG response was lower than the anti-PorB response. These findings indicate that the presence of LPS is not essential for the induction of an antineisserial porin humoral response but can augment such a response. To determine whether LPS has any effect on the B-cell-stimulatory effect of neisserial porins (essential for the adjuvant activity of neisserial porins), B cells from both murine strains were incubated with outer membrane complexes (OMCs) prepared from strain H44/76 and its LPS-negative mutant. OMCs from either meningococcal strain were able to increase the surface expression of the costimulatory ligand B7-2 on B cells from either murine strain. Consistent with previously reported findings, LPS does not significantly affect the ability of neisserial porins to induce the costimulatory ligand B7-2.

Animals↗

PubMed2000

Overexpression of CuZnSOD in coronary vascular cells attenuates myocardial ischemia/reperfusion injury.

Superoxide dismutase scavenges oxygen radicals, which have been implicated in ischemia/reperfusion (I/R) injury in the heart. Our experiments were designed to study the effect of a moderate increase of copper/zinc superoxide dismutase (CuZnSOD) on myocardial I/R injury in TgN(SOD1)3Cje transgenic mice. A species of 0.8 kb human CuZnSOD mRNA was expressed, and a 273% increase in CuZnSOD activity was detected in the hearts of transgenic mice with no changes in the activities of other antioxidant enzymes. Furthermore, immunoblot analysis revealed no changes in the levels of HSP-70 or HSP-25 levels. Immunocytochemical study indicated that there was increased labeling of CuZnSOD in the cytosolic fractions of both endothelial cells and smooth muscle cells, but not in the myocytes of the hearts from transgenic mice. When these hearts were perfused as Langendorff preparations for 45 min after 35 min of global ischemia, the functional recovery of the hearts, expressed as heart rate x LVDP, was 48 +/- 3% in the transgenic hearts as compared to 30 +/- 5% in the nontransgenic hearts (p <.05). The improved cardiac function was accompanied by a significant reduction in lactate dehydrogenase release from the transgenic hearts. Our results demonstrate that overexpression of CuZnSOD in coronary vascular cells renders the heart more resistant to I/R injury.

Animals↗

PubMed2000

Neisseria meningitidis porin PorB interacts with mitochondria and protects cells from apoptosis.

Neisserial porins are strong immune adjuvants and B cell activators. The effect of neisserial porin PorB on activation-induced cell death was investigated, as a potential additional mechanism of the porin's immunopotentiating ability. Neisserial porins interact with target cells to localize intracellularly in the mitochondrial compartment without negatively affecting cellular survival. Pretreatment with Neisseria meningitidis PorB porin decreased or abrogated the mitochondrial damage induced by apoptotic stimuli. In addition, end stage determinants of apoptosis, including DNA breakdown, were diminished by PorB. Immunoprecipitation experiments revealed that PorB interacts with the mitochondrial porin VDAC (voltage-dependent anion channel). The mechanism of the antiapoptotic effect of neisserial porins could be explained by the protein-protein interaction of PorB with VDAC, similar to the interaction of VDAC with antiapoptotic Bcl-2 proteins, resulting in an enhancement of cell survival and continued activation of B cells.

Animals↗

PubMed2000

Functional and structural studies of alpha-crystallin from galactosemic rat lenses.

Chaperone-like activity and structural changes of lens alpha-crystallin from rats fed with galactose at various time intervals have been studied using high-performance liquid chromatograph (HPLC), circular dichroism (CD), and 1-anilinonaphthalene-8-sulfonic acid (ANS) fluorescence emission. It was found that chaperone-like activity of alpha-crystallin from galactose-fed rats toward dithiothreitol (DTT)-induced insulin B aggregation started to decrease after 3 weeks and decreased significantly after 5 weeks. Consistent results were observed in lens morphology, and lens opacity slightly developed after 3 weeks and became obvious after 5 weeks. HPLC analysis for chaperone function showed that the formation of high molecular weight aggregates (HMWA) of alpha-/gamma-crystallins decreases with the increase of galactose-feeding time, revealing that chaperone-like activity is concomitant with the formation of HMWA. Circular dichroism results showed the reduction of beta-sheet structure and loss of microenvironment of aromatic-type amino acids for opaque lenses, indicating alpha-crystallin's secondary and tertiary structure changed with the development of the lens opacity. ANS binding site estimated by Klotz equation showed it is 1.5 times higher at room temperature and is 2.4 times higher at 58 degrees C for age-matched normal alpha-crystallin than for 5-week galactose-fed lens alpha-crystallin, indicating opaque lens alpha-crystallin loses the ability to assemble into an appropriately placed hydrophobic regions. The overall results accordingly indicated that galactose-induced cataractous alpha-crystallin has disordered structure, leading to the loss of its chaperone-like activity.

Anilino Naphthalenesulfonates↗

PubMed2000

Evidence for changing of cosmic ray composition between 10(17) and 10(18) eV from multicomponent measurements

The average mass composition of cosmic rays with primary energies between 10(17) and 10(18) eV has been studied using a hybrid detector consisting of the High Resolution Fly's Eye (HiRes) prototype and the MIA muon array. Measurements have been made of the change in the depth of shower maximum and the muon density as a function of energy. The results show that the composition is changing from a heavy to lighter mix as the energy increases.

Journal Article↗

PubMed2000

Localized brain activation by selective tasks improves specific cognitive functions in humans.

Neuroimaging studies have identified cognitive tasks that can selectively activate specific parts of the brains. However, the subsequent effect of localized brain activation on the cognitive functioning remains unclear. We discovered that after being engaged in the novel picture encoding task to activate hippocampus for 2 min, individuals demonstrated better memory, but not motor function. Similarly, after performing the finger sequencing task to activate the primary motor cortex, individuals showed improvement in motor function, but not in memory. These double dissociation results suggest that when we selectively activate specific part of the brain, the cognitive function mediated by that particular region but not the others can consequently be improved.

Adult↗

PubMed2000

Using technetium-99M dimercaptosuccinic acid renal cortex scintigraphy to differentiate acute pyelonephritis from other causes of fever in patients with spinal cord injury.

OBJECTIVES: To differentiate acute pyelonephritis (APN) from fever due to other sources in patients with spinal cord injury by using technetium-99m dimercaptosuccinic acid (DMSA) renal cortex scintigraphy (DMSA scan). METHODS: A total of 24 patients with spinal cord injury were admitted with fever. DMSA scans were performed on all patients. The final determination of the cause of the fever was based on the medical history, physical examination, laboratory evaluation, and imaging studies. RESULTS: DMSA scan accurately diagnosed APN in 12 patients with inflammation on the DMSA scan. In 5 patients with scarred lesions on the DMSA scans and in 7 patients with negative DMSA scan, the fever was attributed to other causes. The sensitivity and specificity of the DMSA scan for detecting APN were both 100%. CONCLUSIONS: The DMSA scan is a valuable adjunct in the evaluation of fever in patients with SCI.

Acute Disease↗

PubMed1999

The maturase encoded by a group I intron from Aspergillus nidulans stabilizes RNA tertiary structure and promotes rapid splicing.

The AnCOB group I intron from Aspergillus nidulans self-splices, providing the Mg2+ concentration is >/= 15 mM. The splicing reaction is greatly stimulated by a maturase protein encoded within the intron itself. An initial structural and biochemical analysis of the splicing reaction has now been performed. The maturase bound rapidly to the precursor RNA (kon approximately 3 x 10(9) M(-1) min(-1)) and remained tightly bound (koff </= 0.04 min(-1)). The catalytic step of 5' splice-site cleavage occurred at a rate of up to 11 min(-1) under single turnover conditions. The maturase-assisted reaction of heat-denatured RNA proceeded at a rate of about 1 min(-1), arguing that there are early steps of folding that cannot be readily facilitated by the protein. pH analysis revealed a biphasic profile with a pKa of 7.0. The rate of the maturase-assisted reaction was independent of the Mg2+ concentration down to 3 mM. Self-splicing in optimal Mg2+ (>/= 150 mM) was tenfold slower, in part because of the existence of an equilibrium between folded and partially folded RNA. In contrast, the maturase very effectively stabilized tertiary structure in 5 mM Mg2+, a noticeable example being an interaction between the P8 helix and a GNRA sequence that constitutes the L2 terminal loop of the P2 helix. Formation of the 5' splice-site recognition helix was assisted by either the maturase or high concentrations of Mg2+. The maturase was required during splicing so it is not a true chaperone. However, RNase protection assays and kinetic studies suggest that the maturase recognizes and facilitates folding of an intron with limited tertiary structure and even incomplete secondary structure.

Aspergillus nidulans↗

PubMed1999

The formation of oxidatively induced high-molecular-weight aggregate of alpha-/gamma-crystallins.

alpha-/gamma-Crystallin interactions under oxidation with ascorbate-FeCl3-EDTA-H2O2 followed by dialysis have been studied. A high-molecular-weight aggregate (HMWA) composed of alpha- and gamma-crystallin was observed for the mixture of the dialyzed alpha-crystallin and the oxidized gamma-crystallin through gel-filtration chromatography. This illustrates an interaction between alpha-crystallin and partially denatured gamma-crystallin induced by oxidation. No HMWA formation was observed under the condition without dialysis and/or with the addition of catalase to the oxidized gamma-crystallin prior to the addition of alpha-crystallin. More HMWA was formed by oxidized gamma-crystallin followed by the addition of alpha-crystallin than by simultaneous oxidation of both alpha- and gamma-crystallins. Conformational changes of alpha-crystallin during oxidation analyzed by circular dichroism spectra showed that oxidized alpha-crystallin can gradually be restored to an ordered structure through dialysis. The overall results imply that structural changes of both alpha- and gamma-crystallins and dialysis are required to form HMWA. The observation of this oxidatively induced chaperone/substrate complex suggests that an efficient chaperone-like protective action against oxidative insults may exist in vivo.

Animals↗

PubMed1999

Metabolic kinetics of p-aminobenzoic acid in rabbits.

The metabolic kinetics of p-aminobenzoic acid (PABA) in rabbits was studied. PABA is predominantly metabolized by acetylation and glycine conjugation to form p-acetamidobenzoic acid (PAABA), p-aminohippuric acid (PAHA), and p-acetamidohippuric acid (PAAHA). After PABA IV administration (20 mg/kg) to rapid (n=16) and slow (n=8) acetylation rabbits, PABA was eliminated rapidly. The half-lives of PABA were 7.01+/-0.32 min in rapid acetylation rabbits and 7.08+/-0.78 min in slow acetylation rabbits. Significant differences were obtained in formation of PAABA and PAHA formed from PABA in both acetylation phenotype rabbits. The formation fraction of PAABA, formed by acetylation of PABA, was 0.8029+/-0.0267 in rapid acetylators and 0.2385+/-0.0428 in slow acetylators (p<0.001). PAHA formed from PABA was 0.0462+/-0.0102 in rapid acetylators and 0. 6652+/-0.0562 in slow acetylators (p<0.001). Only 0.0156+/-0.0030 of PABA could be detected as PAAHA in rapid acetylation rabbits which was obtained by acetylation of PAHA. After individual IV injection of PAHA, PAAHA, and PAABA to both phenotypes of rabbits, PAABA and PAAHA were eliminated in their unchanged forms whereas PAHA was further acetylated to form PAAHA. The formation fraction of PAAHA formed from the acetylation of PAHA was 0.4408+/-0.0570 in rapid acetylators and 0.0539+/-0.0084 in slow acetylators (p=0.002). From the results obtained, metabolic pathways of PABA show significant differences in both acetylation phenotypes of rabbits. Acetylation is the major metabolic route of PABA in rapid acetylation rabbits, while glycine conjugation is more predominant in slow acetylation rabbits.

4-Aminobenzoic Acid↗