Cervical softening with vaginal misoprostol before intrauterine device insertion.
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Abortifacient Agents, Nonsteroidal↗
Biomedical subjects
Y C Chu
Publications and source records attributed to Y C Chu.
Idiopathic myelofibrosis with extramedullary haemopoiesis involving the urinary bladder in a Chinese lady.
Extramedullary haemopoiesis (EMH) associated with idiopathic myelofibrosis most commonly involves the reticuloendothelial organs, such as the spleen and liver, although ectopic haemopoietic tissue has also been described rarely in the lymph nodes, skin, gastrointestinal tract, pleura, peritoneum, central nervous system, and genital and urinary tracts. We report on a 54-year-old Chinese lady with a long history of idiopathic myelofibrosis who presented with gross haematuria and left hydronephrosis due to EMH in the bladder trigone. Cystoscopic examination revealed a sessile necrotic papillary growth at the trigone, obstructing the left ureteric orifice. Transurethral resection of the bladder tumour was performed, and microscopic examination of the tumour chips demonstrated atypical megakaryocytes, immature granulocytes and normoblasts, confirming the presence of EMH. The residual bladder tumour responded well to low dose radiotherapy, with subsequent disappearance of haematuria and normalization of ultrasonogram findings.
Cell Lineage↗
Hierarchical protein folding: asymmetric unfolding of an insulin analogue lacking the A7-B7 interchain disulfide bridge.
The landscape paradigm of protein folding can enable preferred pathways on a funnel-like energy surface. Hierarchical preferences may be manifest as a nonrandom pathway of disulfide pairing. Stepwise stabilization of structural subdomains among on-pathway intermediates is proposed to underlie the disulfide pathway of proinsulin and related molecules. Here, effects of pairwise serine substitution of insulin's exposed interchain disulfide bridge (Cys(A7)-Cys(B7)) are characterized as a model of a late intermediate. Untethering cystine A7-B7 in an engineered monomer causes significantly more marked decreases in the thermodynamic stability and extent of folding than occur on pairwise substitution of internal cystine A6-A11 [Weiss, M. A., Hua, Q. X., Jia, W., Chu, Y. C., Wang, R. Y., and Katsoyannis, P. G. (2000) Biochemistry 39, 15429-15440]. Although substantially disordered and without significant biological activity, the untethered analogue contains a molten subdomain comprising cystine A20-B19 and a native-like cluster of hydrophobic side chains. Remarkably, A and B chains make unequal contributions to this folded moiety; the B chain retains native-like supersecondary structure, whereas the A chain is largely disordered. These observations suggest that the B subdomain provides a template to guide folding of the A chain. Stepwise organization of insulin-like molecules supports a hierarchic view of protein folding.
Circular Dichroism↗
Prostaglandins may participate in opioidergic and cholinergic control of the diurnal changes of tuberoinfundibular dopaminergic neuronal activity and serum prolactin level in ovariectomized, estrogen-treated rats.
The roles of prostaglandins (PGs) involved in opioidergic, cholinergic, and serotonergic regulation of the diurnal changes of tuberoinfundibular dopaminergic (TIDA) neuronal activities were investigated in ovariectomized, estrogen-treated rats. Treatment with naloxone [10 mg/kg, intraperitoneal (i.p.)], atropine (5 mg/kg, i.p.), or ketanserin (10 mg/kg, i.p.) at either 1200 or 1400 h prevented the afternoon decrease of TIDA neuronal activity and the prolactin (PRL) surge. Intracerebroventricular (i.c.v.) injection of PGE(1) (5 microg/3 microl/rat) at 1500 h significantly reversed the effects of naloxone and atropine, but not that of ketanserin. In ovariectomized, estrogen-primed rats pretreated with indomethacin, i.c.v. injection of either nicotine (10 ng/rat) or fentanyl (10 ng/rat) failed to suppress the TIDA neuronal activity and to stimulate the PRL secretion. These data suggest that PG may be involved in opioidergic and cholinergic control of the diurnal changes of TIDA neuronal activity and the PRL secretion in ovariectomized (OVX) + E(2) rats.
Acetylcholine↗
Activities of monomeric insulin analogs at position A8 are uncorrelated with their thermodynamic stabilities.
Previous studies have demonstrated that the potency and thermodynamic stability of human insulin are enhanced in concert by substitution of Thr(A8) by arginine or histidine. These surface substitutions stabilize the N-terminal alpha-helix of the A chain, a key element of hormone-receptor recognition. Does enhanced stability necessarily imply enhanced activity? Here, we test by structure-based mutagenesis the relationship between the stability and activity of the hormone. To circumvent confounding effects of insulin self-association, A chain analogs were combined with a variant B chain (Asp(B10), Lys(B28), and Pro(B29) (DKP)) to create a monomeric template. Five analogs were obtained by chain combination; disulfide pairing proceeded in each case with native yield. CD and (1)H NMR spectra of the DKP analogs are essentially identical to those of DKP-insulin, indicating a correspondence of structures. Receptor binding affinities were determined by competitive displacement of (125)I-insulin from human placental membranes. Thermodynamic stabilities were measured by CD titration; unfolding was monitored as a function of guanidine concentration. In this broader collection of analogs receptor binding affinities are uncorrelated with stability. We suggest that receptor binding affinities of A8 analogs reflect local features of the hormone-receptor interface rather than the stability of the free hormone or the intrinsic C-capping propensity of the A8 side chain.
Amino Acid Sequence↗
Isotope-edited Raman spectroscopy of proteins: a general strategy to probe individual peptide bonds with application to insulin.
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Insulin↗
Prostaglandins play an important role in diurnal changes of tuberoinfundibular dopaminergic neuronal activity and prolactin secretion in ovariectomized, estrogen-treated rats.
Intracerebroventricular injection of prostaglandins (PGs) has long been shown to stimulate the secretion of prolactin (PRL). The action of specific PG and the underlying mechanism, however, remain inconclusive. In this study, we evaluated the involvement of PGs in the diurnal changes of the tuberoinfundibular dopaminergic (TIDA) neurons and PRL secretion in ovariectomized (OVX) rats treated with estrogen (E2). Prior treatment of indomethacin (50 mg/kg, subcutaneous) for 24 h significantly prevented the afternoon decrease of TIDA neuronal activity and blocked the PRL surge. Intracerebroventricular injection of PGE(1) (5 microg/3 microl/rat) at 1000 h significantly lowered the activity of TIDA neurons, while similar treatment of PGE2 was without effect. In OVX + E(2) rats pretreated with indomethacin, PGE(1) given at 15, but not 30 or 180 min before decapitation at 1500 h significantly reversed the effects of indomethacin on TIDA neuronal activity, while the blocked PRL surge was not reversed. The PGs also exhibited a stimulatory effect on nigrostriatal dopamine (DA) neurons with PGE2 being the most effective agent. These results indicate that endogenous PGs play a significant role in the control of central DA neurons, especially the diurnal changes of TIDA neuronal activity and PRL secretion in OVX + E2 rats.
3,4-Dihydroxyphenylacetic Acid↗
Chinese writing function in patients with left versus right putaminal hemorrhage.
This study was designed to explore the Chinese writing function of patients with subcortical stroke. Two cohorts of patient subjects with either the left or the right subcortical strokes, mainly putaminal hemorrhagic strokes, and one group of normal controls participated in the study. All participants received a writing test battery including the three aspects of writing function, that is, Spontaneous Writing, Writing to Dictation, and Writing from Copy, as well as a battery of non-writing linguistic tests. Comparing with normal controls revealed that writing function change occurred in both patient groups. The deficits in the patients with the left subcortical stroke essentially included Spontaneous Writing, and Writing to Dictation. These impairments were most likely secondary to aphasic disorders. The writing problem, mainly Writing from Copy, was noted in the patients with the right subcortical stroke. This deficit, however, was independent of the core linguistic impairment. On the basis of the results, we suggest that the lesion involving white matter in the left hemisphere probably interrupts left perisylvian cortical language organization in a manner that produces problems with spontaneous writing and writing to dictation, which are language-related, associated with lesion in the dominant hemisphere. This further suggests that left or right subcortical lesions in the putamen and surrounding white matter are associated with differential effects (language vs. non-language based effects) which are similar to such differences observed with left vs. right cortical lesions.
Adult↗
Anesthetic management of parturients with Eisenmenger's syndrome--report of two cases.
Pregnancy is badly tolerated in patients with Eisenmenger's syndrome; maternal mortality with coherent fetal morbidity is high. Even with the advancement of both obstetric and anesthetic managements, the maternal mortality still exceeds 25%. Once conception occurs in patients of Eisenmenger's syndrome with severe pulmonary hypertension, interruption of pregnancy is still the best manipulation to be recommended. We report two cases of parturients with Eisenmenger's syndrome, who underwent termination of pregnancy. In this report, the obstetric and anesthetic management of this kind of parturients with Eisenmenger's syndrome has been thoroughly discussed.
Adult↗
Reversal of mivacurium chloride: edrophonium of spontaneous recovery in microscopic laryngeal surgery.
BACKGROUND: A double-blind, randomized study was designed to compare the recovery manner of mivacurium infusion with or without edrophonium reversal in microscopic laryngeal surgery. Neuromuscular blockade was quantified using the train-of-four stimuli to the ulnar nerve and quantification of the ratio of the fourth twitch to the first twitch. METHODS: With the approval of the Human Studies Committee of the Taipei Veterans General Hospital and patient informed consent, 40 healthy (ASA I or II) patients with age from 24 to 54 years, undergoing microscopic laryngeal surgery were randomly selected for study. Mivacurium chloride 0.2 mg/kg was given intravenously, and then it was given in continuous infusion to maintain muscle relaxation at 90% twitch block during the procedure. At the end of operation, mivacurium infusion was terminated. In a double-blind manner, group I patients (n = 20) received intravenous edrophonium 1 mg/kg and atropine 0.01 mg/kg for reversal when T1 was at 10% recovery whereas patients in Group II (n = 20) received placebo in the same manner. Mean infusion rate, recovery index (RI50, time from T1 25% to T1 50%; RI75, time from T1 25% to T1 75%), extubation time, and discharge time between groups were compared. Nausea, vomiting, and dysrhythmias were also documented until the patient was discharged from hospital. RESULTS: The demographic data between two groups were similar. The recovery index (RI75) for group I was shorter than that of placebo group (5.3 +/- 2.19 min vs. 7.3 +/- 0.9 min) and the difference was statistically significant (P = 0.017). There were no statistically significant differences in mean infusion rate, incidence of nausea and vomiting, and discharge time from the POR. The incidence of tachycardia or arrhythmia in group I was significantly greater than that in group placebo. CONCLUSIONS: Mivacurium, a short-acting nondepolarizing agent, is a suitable muscle relaxant for patients receiving microscopic laryngeal surgery. Recovery time with the use of edrophonium as reversal agent was shorter than with placebo, but extubation and discharge time did not differ in two groups. The time which could be saved by the use of edrophonium for reversal of mivacurium to hasten the maximal recovery appears to be less than a few minutes. Therefore, clinically, the value of routine use of edrophonium to obtain a faster recovery does not outweigh its demerits of cost and risk and is not worthy of recommendation.
Adult↗
Hierarchical protein "un-design": insulin's intrachain disulfide bridge tethers a recognition alpha-helix.
A hierarchical pathway of protein folding can enable segmental unfolding by design. A monomeric insulin analogue containing pairwise substitution of internal A6-A11 cystine with serine [[Ser(A6),Ser(A11),Asp(B10),Lys(B28),Pro(B29)]insulin (DKP[A6-A11](Ser))] was previously investigated as a model of an oxidative protein-folding intermediate [Hua, Q. X., et al. (1996) J. Mol. Biol. 264, 390-403]. Its structure exhibits local unfolding of an adjoining amphipathic alpha-helix (residues A1-A8), leading to a 2000-fold reduction in activity. Such severe loss of function, unusual among mutant insulins, is proposed to reflect the cost of induced fit: receptor-directed restoration of the alpha-helix and its engagement in the hormone's hydrophobic core. To test this hypothesis, we have synthesized and characterized the corresponding alanine analogue [[Ala(A6),Ala(A11),Asp(B10),Lys(B28), Pro(B29)]insulin (DKP[A6-A11](Ala))]. Untethering the A6-A11 disulfide bridge by either amino acid causes similar perturbations in structure and dynamics as probed by circular dichroism and (1)H NMR spectroscopy. The analogues also exhibit similar decrements in thermodynamic stability relative to that of the parent monomer as probed by equilibrium denaturation studies (Delta Delta G(u) = 3.0 +/- 0.5 kcal/mol). Despite such similarities, the alanine analogue is 50 times more active than the serine analogue. Enhanced receptor binding (Delta Delta G = 2.2 kcal/mol) is in accord with alanine's greater helical propensity and more favorable hydrophobic-transfer free energy. The success of an induced-fit model highlights the applicability of general folding principles to a complex binding process. Comparison of DKP[A6-A11](Ser) and DKP[A6-A11](Ala) supports the hypothesis that the native A1-A8 alpha-helix functions as a preformed recognition element tethered by insulin's intrachain disulfide bridge. Segmental unfolding by design provides a novel approach to dissecting structure-activity relationships.
Amino Acid Sequence↗
Specific induction of glutathione S-transferase GSTM2 subunit expression by epigallocatechin gallate in rat liver.
The antitumor effect of green tea polyphenols has been well characterized in numerous papers. However, the mechanism of their action is still poorly defined. In this study, epigallocatechin gallate (EGCG), the main ingredient of green tea extract, was studied for its effect on the expression of glutathione S-transferases (GSTs) in rat liver to examine the mechanism of action. Liver samples were collected from Sprague-Dawley rats treated with EGCG in H(2)O by portal vein perfusion and examined for total GST activity and GST expression. The results showed that the induction of GST activity by EGCG was dose- and time-dependent. GST activity was increased about 28-fold at 12 hr after treatment. Three GST subunits (GSTA1/2, GSTM1, and GSTM2) were examined by Western blot for changes in protein level affected by EGCG (1 mg/kg weight). Only GSTM2 revealed a significant time-dependent increase, with a maximal induction of approximately 2.0-fold. The differential effect of EGCG on GST subunit expression was also verified by immunocytochemical examination and showed strong induction of the GSTM2 (but not the GSTA1/2 and GSTM1) level in liver section. This induction occurred as early as 3 hr after treatment and extended gradually outward from the hepatic veins as treatment time increased. The change in the GSTM2 protein level was accompanied by a corresponding alteration in mRNA quantity ( approximately 2.0-fold of control). Our report is the first to demonstrate a specific induction of the GSTM2 subunit by a chemopreventor and suggests a primary influence of EGCG on GSTM2 gene expression.
Animals↗
Cloning and expression of ZAK, a mixed lineage kinase-like protein containing a leucine-zipper and a sterile-alpha motif.
A novel mixed lineage kinase-like protein ZAK, containing a leucine-zipper (LZ) and a sterile-alpha motif (SAM), was cloned. This cDNA has 2456 bp and encodes a protein of 800 amino acids that contains a kinase catalytic domain, a leucine-zipper and a SAM. The molecular weight of this protein is 91kDa. Northern blot analysis revealed that the expression of this ZAK gene is found in various parts of human tissues. We also found that ZAK proteins might form homodimers or oligomers in mammalian cells. MLKs have been proposed to function as mitogen-activated protein kinase kinase kinase in pathways leading to MAPK cascade. The expression of ZAK in mammalian cells specifically leads to the activation of the JNK/SAPK pathway as well as the activation of transcription factor, NF-kappaB. Overexpression of the ZAK gene induces the apoptosis of a hepatoma cell line.
Amino Acid Sequence↗
Myositis ossificans of the chest wall simulating malignant neoplasm.
Myositis ossificans originating from the chest wall is extremely rare. We report a case of myositis ossificans occurring in a young woman with progressive painful swelling in the chest wall. Preoperative examination suggested a malignant neoplasm originating from soft tissue. Although rare, myositis ossificans is one of the potential causes of painful swelling in the chest wall, and can be mistaken for a malignant neoplasm.
Adolescent↗
The management of isolated thrombocytopenia in Chinese adults: does bone marrow examination have a role at presentation?
We performed a retrospective analysis of bone marrow examination (BME) in the management of Chinese adult patients less than 60 years of age with isolated thrombocytopenia at presentation. Eighty-three patients with a median age of 39 years presenting with isolated thrombocytopenia (median platelet count: 38 x 10(9)/l) had routinely undergone BME as part of the laboratory investigations during the period from January 1996 to December 1999. All 83 patients had bone marrow findings of active marrow suggesting causes due to peripheral destruction. All of these patients responded to steroid or intravenous immunoglobulin (IVIg) therapy at presentation if their platelet counts were significantly low or if they had mucosal bleeding. Eighty-one of the 83 patients, after a median of 20 months follow-up, were finally diagnosed as having idiopathic thrombocytopenic purpura (ITP). The remaining two patients were finally confirmed as cases of systemic lupus erythematosus (SLE). Our results suggest that BME is not helpful in the diagnosis of isolated thrombocytopenia or suspected ITP in adult patients at presentation, provided that a thorough clinical history and physical examination are undertaken and that the blood count and peripheral blood smear show no abnormalities apart from the thrombocytopenia.
Adolescent↗
Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma.
BACKGROUND AND AIMS: ras Gene and its product (p21) have been reported to be associated with vascular endothelial growth factor (VEGF), which is one of the most important angiogenic factors, and tumor-associated angiogenesis. We tried to evaluate the correlation between the expression of c-H-ras gene product p21 and angiogenesis in advanced gastric carcinoma. METHODS: Immunohistochemical expression of c-H-ras p21 and VEGF was examined in 49 advanced gastric adenocarcinomas. In addition, double immunohistochemical staining was performed using anti-CD34 and anti-Ki-67 antibodies, and the intratumoral microvessel densities and their endothelial proliferative labeling indices were then counted to evaluate the degree of angiogenesis. RESULTS: The expression of c-H-ras p21 was demonstrated in 43 out of 49 gastric adenocarcinomas (87.8%). It did not correlate with histologic type, depth of invasion or metastasis. However, the degree of c-H-ras p21 expression was correlated with VEGF. In addition, the degree of c-H-ras p21 expression was correlated with increased intratumoral microvascular density and endothelial proliferative activity. CONCLUSIONS: We suggest that c-H-ras oncogene product p21 contributes to the upregulation of tumor-associated angiogenesis by the increased production of VEGF in advanced gastric carcinomas. Therefore, treatment involving the targeting of ras oncogene could inhibit solid tumor growth by suppressing tumor-associated angiogenesis.
Adenocarcinoma↗
Churg-Strauss syndrome with perforating ulcers of the colon.
We report a case of a 72-year-old woman with Churg-Strauss syndrome, who presented with intestinal perforation. She has had bronchial asthma with peripheral blood eosinophilia for 30 years. Gross findings of a resected colon showed multiple ulcers with perforation. Histologic findings demonstrated transmural inflammation infiltrated with large numbers of eosionophils, neutrophils and lymphoplasma cells, and characteristic extravascular granuloma in the subserosa. There were multifocally-distributed transmural vasculitis showing all stages of activity in medium and small-sized arteries and veins located in the submucosa, and proper muscle and subserosal layers of the colon, some of which revealed granulomatous inflammation. Histologic finding of liver showed chronic viral hepatitis B with mild inflammatory activity and macronodular cirrhosis. Immunohistochemical findings, acid fuschin orange G staining and electromicroscope found no evidence of hepatitis B virus infection contributing to the pathogenesis of this lesion.
Aged↗
Metastatic renal cell carcinoma in a meningioma: a case report.
Tumor-to-tumor metastasis is rare. We report a case of metastatic renal cell carcinoma in meningioma. A 67-year-old woman presented a two-week history of motor dysphagia and decreased short-term memory. She had undergone a left radical nephrectomy for a renal cell carcinoma 7 years ago, and had not received any adjuvant therapy. MRI disclosed a 3.0 x 3.0 x 3.0-cm sized round tentorial-based extraaxial mass with peritumoral edema in the left posterior temporal lobe. During operation, the tumor was found to be an encapsulated mass firmly attached to the tentorium. Histologically, the tumor was a meningotheliomatous meningioma extensively infiltrated by metastatic renal cell carcinoma, accompanying widespread coagulative necrosis. Immunohistochemical staining for cytokeratin revealed strong positivity only in the renal cell carcinoma component. The patient's postoperative course was uneventful. Post-operative radiation therapy was applied to the whole brain. Three months after operation, the patient developed right hemiparesis and dysphagia. Brain MRI at that time did not reveal recurrence or any other causative lesions, although the whole body scan disclosed uptake at the second lumbar vertebra and rib. The patient refused further treatment.
Aged↗