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Biomedical subjects

S C Hsu

Publications and source records attributed to S C Hsu.

At least 19 recordsLinked to original sources

The molecular mechanisms of the mammalian exocyst complex in exocytosis.

Exocytosis is a highly ordered vesicle trafficking pathway that targets proteins to the plasma membrane for membrane addition or secretion. Research over the years has discovered many proteins that participate at various stages in the mammalian exocytotic pathway. At the early stage of exocytosis, co-atomer proteins and their respective adaptors and GTPases have been shown to play a role in the sorting and incorporation of proteins into secretory vesicles. At the final stage of exocytosis, SNAREs (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) and SNARE-associated proteins are believed to mediate the fusion of secretory vesicles at the plasma membrane. There are multiple events that may occur between the budding of secretory vesicles from the Golgi and the fusion of these vesicles at the plasma membrane. The most obvious and best-known event is the transport of secretory vesicles from Golgi to the vicinity of the plasma membrane via microtubules and their associated motors. At the vicinity of the plasma membrane, however, it is not clear how vesicles finally dock and fuse with the plasma membrane. Identification of proteins involved in these events should provide important insights into the mechanisms of this little known stage of the exocytotic pathway. Currently, a protein complex, known as the sec6/8 or the exocyst complex, has been implicated to play a role at this late stage of exocytosis.

Animals↗

Experimental identification of the kink instability as a poloidal flux amplification mechanism for coaxial gun spheromak formation.

The magnetohydrodynamic kink instability is observed and identified experimentally as a poloidal flux amplification mechanism for coaxial gun spheromak formation. Plasmas in this experiment fall into three distinct regimes which depend on the peak gun current to magnetic flux ratio, with (I) low values resulting in a straight plasma column with helical magnetic field, (II) intermediate values leading to kinking of the column axis, and (III) high values leading immediately to a detached plasma. Onset of column kinking agrees quantitatively with the Kruskal-Shafranov limit, and the kink acts as a dynamo which converts toroidal to poloidal flux. Regime II clearly leads to both poloidal flux amplification and the development of a spheromak configuration.

Journal Article↗

Effect of hormone replacement therapy on uterine fibroids in postmenopausal women--a 3-year study.

OBJECTIVE: The aim of this prospective 3-year clinical study was to examine the effect of hormone replacement therapy (HRT) on uterine fibroid growth among postmenopausal women. METHODS: Thirty-seven postmenopausal women with uterine solitary fibroids were recruited randomly for HRT in a 3-year program. All participants received 0.625 mg conjugated equine estrogen (CEE) and 5 mg medroxyprogesterone (MPA) daily. Fibroid volume was measured by transvaginal ultrasonography at baseline and then at 12-month intervals for 3 times. Clinically, significant fibroid growth was defined as an increase in volume of more than 25% compared with baseline. Also, 35 postmenopausal women with uterine fibroid were studied as control who did not receive HRT during the study period. RESULTS: Fibroid volume had increased significantly after 1 year both in HRT users and non-users. These increases continued to the second year significantly in HRT users but not in non-users. However, the volumes declined significantly at the third year to similar levels as those measured at baseline in control. In HRT users, fibroid volume though significantly increased at the third year (vs. baseline) but declined insignificantly in comparison with the second year. Clinically, at end of the third year study, one of 34 and three of 34 women increased fibroid volume over 25% compared with baseline in HRT non-users and users, respectively. CONCLUSIONS: HRT does increase uterine fibroid volume statistically. However, its effect appears in the first 2 years of use. The increased fibroid volume begins to decline at the third year both in HRT users and non-users. Clinically, the increased effect of HRT on uterine fibroid of postmenopausal women should be not over-emphasized at least for 3 years of usage.

Adult↗

Changes in vesicourethral function following laparoscopic hysterectomy versus abdominal hysterectomy.

OBJECTIVE: To assess whether total hysterectomy is associated with increased postoperative vesicourethral abnormalities. SAMPLE: Forty-five patients had a laparoscopic hysterectomy and 36 patients had a total abdominal hysterectomy. DESIGN: Before and after hysterectomy, patients underwent a urinalysis, a personal interview, and an urodynamic study. RESULTS: Of the laparoscopic hysterectomy group, 27 patients (60%) exhibited urinary symptoms preoperatively, and 22 patients (48.9%) remained symptomatic following surgery. There was no significant change in the number of women with one or more urinary symptoms, but the incidence of urinary frequency and stress incontinence decreased significantly following hysterectomy (p < 0.05). Of the total abdominal hysterectomy group, preoperative voiding symptoms were present in 22 patients (61.1%). After surgery, urinary symptoms were present in 19 patients (52.8%). Some patients did not complain of any urinary frequency or stress incontinence following hysterectomy, but this figure did not differ significantly (p > 0.05). Maximal urethral closure pressure and maximal cystometric capacity demonstrated significant increases for both groups following surgery. CONCLUSIONS: The results indicated that total hysterectomy, either laparoscopic or total abdominal hysterectomy, did not significantly increase the subjective and objective incidence of vesicourethral dysfunction. On the contrary, some patients experience a substantial improvement of pre-existing urinary frequency or stress incontinence, partly as a result of an increase in the maximal urethral closure pressure and total bladder capacity following hysterectomy.

Female↗

Systemic lupus erythematosus presented as non-inflammatory necrotizing vasculopathy-induced ischemic glomerulopathy and small vessels-related ischemic cardiomyopathy.

The clinical significance of lupus non-inflammatory necrotizing vasculopathy (NINV) is not well established. For example, since lupus renal NINV is usually reported to coexist with proliferative and active glomerulonephritis, it is difficult to demonstrate the role of NINV on renal pathophysiology. Here we report a 16-year-old SLE boy with renal NINV presenting as ischemic glomerulopathy and small vessels-related ischemic heart failure. The renal biopsy demonstrated mild proliferative glomerulonephritis and NINV initially, and one month later repeated renal biopsy showed NINV with ischemic glomerulopathy. These findings established that NINV, but not proliferative glomerulonephritis, was responsive for his acute renal failure (ARF). Another interesting question is about the pathophysiology of his myocardial dysfunction. This patient presented typical angina and congestive heart failure (CHF). Echocardiograms and ventriculography revealed dilatation of four chambers and low ejection fraction. Serial electrocardiograms demonstrated evolutionary ischemic changes. Coronary angiography revealed no abnormality of large vessels. These findings suggested small vascular lesions-induced myocardial ischemia was the underlying mechanism of dilated cardiomyopathy. As myocardial biopsy was not done in our case, we could only speculate, but not prove, that the NINV observed in renal biopsy may also involve in cardiac microvascular beds. Nevertheless, this interesting case emphasized the role of obliterative small vascular lesions in the pathophysiology of ARF and myocardial dysfunction. The patient was treated with high-dose corticosteroid, plasma infusion and hemodialysis. His cardiac function improved gradually, however the renal function did not recover.

Acute Kidney Injury↗

Observation of B --> J/psi K(1)(1270).

We report the first observation of the exclusive decay process B-->J/psi K(1)(1270) using a sample of 11.2M BB macro meson pairs collected in the Belle detector at the KEKB asymmetric energy e(+)e(-) collider. We measure branching fractions of B[B(0)-->J/psi K(0)(1)(1270)] = (1.30+/-0.34+/-0.32) x 10(-3) and B[B(+)-->J/psi K(+)(1)(1270)] = (1.80+/-0.34+/-0.39) x 10(-3), where the first error is statistical and the second is systematic. These modes constitute approximately 15% of the total number of B-->J/psi X decays. No evidence is seen for B-->J/psi K(1)(1400) and we set an upper limit for this branching fraction.

Journal Article↗

Observation of Cabibbo suppressed B --> D(*)K- decays at Belle.

We report observations of the Cabibbo suppressed decays B-->D((*))K- using a 10.4 fb(-1) data sample accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB e(+)e(-) storage ring. We find that the ratios of Cabibbo suppressed to Cabibbo favored branching fractions are B(B--->D0K-)/B(B--->D0pi(-)) = 0.079+/-0.009+/-0.006, B(B(0)-->D+K-)/B(B(0)-->D+pi(-)) = 0.068+/-0.015+/-0.007, B(B--->D(*0)K-)/B(B--->D(*0)pi(-)) = 0.078+/-0.019+/-0.009, and B(B(0)-->D(*+)K-)/B(B(0)-->D(*+)pi(-)) = 0.074+/-0.015+/-0.006. These are the first observations of the B-->D+K-, D(*0)K-, and D(*+)K- decay processes.

Journal Article↗

Observation of large CP violation in the neutral B meson system.

We present a measurement of the standard model CP violation parameter sin2 phi(1) based on a 29.1 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. One neutral B meson is fully reconstructed as a J/psi K(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psi K(L), or J/psi K(*0) decay and the flavor of the accompanying B meson is identified from its decay products. From the asymmetry in the distribution of the time intervals between the two B meson decay points, we determine sin2 phi(1) = 0.99+/-0.14(stat)+/-0.06(syst). We conclude that we have observed CP violation in the neutral B meson system.

Journal Article↗

Rescue of a Wnt mutation by an activated form of LEF-1: regulation of maintenance but not initiation of Brachyury expression.

Members of the LEF-1/TCF family of transcription factors have been implicated in mediating a nuclear response to Wnt signals by association with beta-catenin. Consistent with this view, mice carrying mutations in either the Wnt3a gene or in both transcription factor genes Lef1 and Tcf1 were previously found to show a similar defect in the formation of paraxial mesoderm in the gastrulating mouse embryo. In addition, mutations in the Brachyury gene, a direct transcriptional target of LEF-1, were shown to result in mesodermal defects. However, direct evidence for the role of LEF-1 and Brachyury in Wnt3a signaling has been limiting. In this study, we genetically examine the function of LEF-1 in the regulation of Brachyury expression and in signaling by Wnt3a. Analysis of the expression of Brachyury in Lef1(-/-)Tcf1(-/-) mice and studies of Brachyury:lacZ transgenes containing wild type or mutated LEF-1 binding sites indicate that Lef1 is dispensable for the initiation, but is required for the maintenance of Brachyury expression. We also show that the expression of an activated form of LEF-1, containing the beta-catenin activation domain fused to the amino terminus of LEF-1, can rescue a Wnt3a mutation. Together, these data provide genetic evidence that Lef1 mediates the Wnt3a signal and regulates the stable maintenance of Brachyury expression during gastrulation.

Animals↗

Glycogen synthase kinase-3beta regulates presenilin 1 C-terminal fragment levels.

The majority of familial Alzheimer's disease cases have been attributed to mutations in the presenilin 1 (PS1) gene. PS1 is synthesized as an inactive holoprotein that undergoes endoproteolytic processing to generate a functional N- and C-terminal heterodimer (NTF and CTF, respectively). We identified a single residue in PS1, Ser(397), which regulates the CTF levels in a population of dimer that has a rapid turnover. This residue is part of a highly conserved glycogen synthase kinase-3beta (GSK-3beta) consensus phosphorylation site within the loop domain of PS1. Site-directed mutagenesis at the Ser(397) position increased levels of PS1 CTF but not NTF or holoprotein. Similar increases in only CTF levels were seen when cells expressing wild type PS1 were treated with lithium chloride, an inhibitor of GSK-3beta. Both wild type and PS1 S397A CTF displayed a biphasic turnover, reflecting rapidly degraded and stable populations. Rapid turnover was delayed for mutant PS1 S397A, causing increased CTF. These data demonstrate that PS1 NTF.CTF endoproteolytic fragments are generated in excess, that phosphorylation at Ser(397) by GSK-3beta regulates the discard of excess CTF, and that the disposal of surplus NTF is mediated by an independent mechanism. Overall, the results indicate that production of active NTF.CTF dimer is more complex than limited endoproteolysis of PS1 holoprotein and instead involves additional regulatory events.

Amino Acid Motifs↗

The exocyst complex associates with microtubules to mediate vesicle targeting and neurite outgrowth.

During neuronal development, vesicles are targeted to the growth cone to promote neurite outgrowth and synaptogenesis. The Exocyst complex is an essential macromolecule in the secretory pathway that may play a role in vesicle targeting. Although it has been shown that this complex is enriched in rat brain, the molecular mechanism underlying its function is largely unknown. Here, we report that the Exocyst complex coimmunoprecipitates with microtubules from total rat brain lysate. Additionally, the Exocyst complex subcellular localization changes on neuronal differentiation. In undifferentiated pheochromocytoma (PC12) cells, this complex is associated with microtubules at the microtubule organizing center. However, in differentiated PC12 cells and cultured hippocampal neurons, the Exocyst complex and microtubules extend to the growing neurite and colocalize at the growth cone with synaptotagmin. Inhibition of the NGF-activated MAP kinase pathway blocks the Exocyst complex and microtubule redistribution, abolishing neurite outgrowth and promoting cytosolic accumulation of secretory vesicles. Consistently, the overexpression of Exocyst sec10 subunit mutant blocks neurite outgrowth. These results indicate that the Exocyst complex targets secretory vesicles to specific domains of the plasma membrane through its association with the microtubules, promoting neurite outgrowth.

Animals↗

Measurement of B(0)(d)-B_(0)(d) mixing rate from the time evolution of dilepton events at the upsilon(4S).

We report a determination of the B(0)(d)-&B_(0)(d) mixing parameter Deltam(d) based on the time evolution of dilepton yields in Upsilon(4S) decays. The measurement is based on a 5.9 fb(-1) data sample collected by the Belle detector at KEKB. The proper-time difference distributions for same-sign and opposite-sign dilepton events are simultaneously fitted to an expression containing Deltam(d) as a free parameter. Using both muons and electrons, we obtain Deltam(d) = 0.463+/-0.008 (stat)+/-0.016 (syst) ps(-1). This is the first determination of Deltam(d) from time evolution measurements at the Upsilon(4S). We also place limits on possible CPT violations.

Journal Article↗

Measurement of the CP violation parameter sin2 phi(1) in B(0)(d) meson decays.

We present a measurement of the standard model CP violation parameter sin2 phi(1) (also known as sin2beta) based on a 10.5 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric e(+)e(-) collider. One neutral B meson is reconstructed in the J/psiK(S), psi(2S)K(S), chi(c1)K(S), eta(c)K(S), J/psiK(L), or J/psipi(0) CP-eigenstate decay channel and the flavor of the accompanying B meson is identified from its charged particle decay products. From the asymmetry in the distribution of the time interval between the two B-meson decay points, we determine sin2 phi(1) = 0.58(+0.32)(-0.34)(stat)+0.09-0.10(syst).

Journal Article↗

PCR primers designed from malic acid dehydrogenase gene and their use for detection of Escherichia coli in water and milk samples.

Escherichia coli has been the appropriate focus for monitoring of potential enteric pathogens in water and foods. Although several methods have been used for the detection or enumeration of E. coli cells in water and foods, the time and accuracy limitations of these methods suggest the need of a rapid and specific method. By comparison of the gene sequences coding for malic acid dehydrogenase (mdh) of E. coli and non-E. coli strains, two oligonucleotides were designed and their possible use as E. coli-specific PCR primers was tested. All of the 110 E. coli strains tested, including non-pathogenic and various pathogenic strains, generated the expected PCR products with Mw equal to 392 bp. On the other hand, only 97 of these 110 E. coli strains were detectable using the BAM gas production method. With the exception of Shigella strains, non-E. coli strains, including strains of the family of Enterobacteriaceae, did not generate any false positive PCR results. When this PCR system was used for the monitoring of E. coli cells inoculated into water and milk samples, as low as 10(0) cfu per 100 ml of water or per ml of milk sample could be detected if an 8 h preculture step was performed prior to the PCR. Including the preculture step, the whole PCR detection process may be completed within 12 h.

Animals↗

Seroprevalence and demographic characteristics of HTLV-I among blood donors in Taiwan: 1996-1999.

Screening for the human T-cell lymphotropic virus type I (HTLV-I) and-II in blood donors was implemented in Taiwan beginning in February 1996. The purpose of the present study was to investigate the changes in HTLV-I seroprevalence in all unpaid blood donors in Taiwan during the period from February 1996 to December 1999 and to determine the influence of age and sex on the HTLV-I seropositivity of donors. HTLV-I and HTLV-II screening was performed using combined HTLV-I/II immunoassay. Repeated reactive samples were confirmed by Western blot analysis. Of a total of 3,701,087 donors in all 6 blood centers in Taiwan, 2,311 (0.058%) were seropositive for HTLV-I. The HTLV-I seropositivity was 0.130%, 0.063%, 0.044%, and 0.032% in the years 1996, 1997,1998, and 1999, respectively. There was a linear increase of HTLV-I seropositivity with advancing age. The HTLV-I carrier rate for female donors was twice that for the male donors. Ninty-seven percent of HTLV-I seropositive results came from first-time donors. Our findings suggest that Taiwan is a low-prevalence nonendemic area for HTLV-I infection. The large-scale HTLV-I screening program has decreased HTLV-I seropositivity among blood donors and is useful for preventing HTLV-I transmission via blood transfusion.

Adolescent↗