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Biomedical subjects

C Yu

Publications and source records attributed to C Yu.

At least 217 records · Page 12Linked to original sources
PubMed1998

A comparison of laboratory data in perinatal transfers at Baystate Medical Center and transferring hospitals.

Objective: Perinatal transfers come to Baystate Medical Center (BMC), a tertiary hospital with level III nursery, for treatment of pregnancy-related complications such as preterm labor, PPROM, PIH, diabetes, and bleeding problems. We postulated that Baystate Medical Center, a teaching hospital, must repeat most of the laboratory tests ordered by the community hospitals transferring these pregnant patients.Methods: A comparison of laboratory tests ordered by the transferring hospital and Baystate Medical Center was done in a retrospective chart review. Among the 92 charts reviewed, 42 perinatal transfer patients with PTL and PPROM, excluding patients with diabetes, PIH, and other complications, were included in the study.Results: A significant difference (P <.001 by Student t test) was found between the number of laboratory tests ordered by Baystate Medical Center and the outside hospital. Ten laboratory tests, such as white count, hematocrit, differential, cervical cultures, urinalysis and culture, tox screen, type and screen, and ultrasounds, were ordered by BMC in comparison to only three laboratory tests ordered by the transferring doctors. In comparing patients directly admitted to Baystate for PTL or PPROM with the perinatal transfer patients, there was no significant difference between the number of laboratory tests ordered. However, perinatal transfers had a greater percentage of PPROM and delivery prior to 36 weeks.Conclusion: In conclusion, there is limited redundancy in laboratory testing in perinatal transfer patients when they are transferred from one institution to the another. Diagnosis of PTL is difficult and a panel of laboratory tests have become standards in finding causes at BMC. Allowing the tertiary hospital to work up the perinatal transfer patients is an efficient way of allocating health care.

Journal Article↗
PubMed1998

Current and future preparative regimens for bone marrow transplantation in thalassemia.

Preparative regimens for marrow allografts in thalassemia have two objectives. One is eradication of diseased marrow and the other suppression of host-versus-graft (HVG) reactions so that the allograft survives. A common regimen to accomplish these goals has combined high-dose busulfan with cyclophosphamide. Postgrafting immunosuppression with cyclosporine/methotrexate has been used for GVHD prevention. Some patients may die from regimen-related toxicity. Overall event-free survival is 75%. Occasional patients have become mixed donor/host hematopoietic chimeras and, yet, disease symptoms have abated. This has raised the possibility of developing safer and less toxic transplant programs that result in stable mixed hematopoietic chimerism. We have devised such a program in dogs consisting of a nonlethal dose of total body irradiation (200 cGy) before and a novel combination of mycophenolate mofetil and cyclosporine after transplant. Mixed donor/host chimerism (> or = 50% donor cells in all lineages) has persisted for > 80 weeks, even though immunosuppression was discontinued after five weeks.

Animals↗
PubMed1998

Unfolding and refolding of cardiotoxin III elucidated by reversible conversion of the native and scrambled species.

Cardiotoxin analogue III (CTX III) isolated from the venom of the Taiwan Cobra (Naja naja atra) is a small molecular weight, all beta-sheet protein, cross-linked by four disulfide bridges. The unfolding and refolding mechanisms of CTX III have been examined by monitoring the reversible conversion of the native and scrambled species. It is found that, in the presence of a denaturant (urea/guanidinium hydrochloride) and a thiol catalyst, CTX III forms a mixture of scrambled species by shuffling its four native disulfide bonds. Complete unfolding of CTX III can be achieved using either 3.0-4.0 M guanidinium hydrochloride (GdmCl) or 5.0-6.0 M urea. It is observed that GdmCl is thermodynamically more potent but kinetically less efficient than urea in unfolding CTX III. The rate constants of unfolding of CTX III in 8 M urea are significantly greater than that obtained in 5.0 M GdmCl and 8.0 M GdmCl. Interestingly, upon removal of the denaturant, scrambled species of CTX III is found to refold spontaneously through dynamic reshuffling of the non-native disulfides to attain the native disulfide linkages. In addition, CTX III contains highly reactive lysines which are modified by trace amounts of cyanate contaminant which exists invariably even in high-grade urea solutions. The reactive lysines of CTX III are modified by cyanate both in the native and unfolded states of the protein. The modification is nonselective, and the modified product is found to consist of highly heterogeneous species. Surprisingly, these heterogeneous species of modified CTX III are observed to display stability and folding/unfolding properties indistinguishable from those of the native CTX III. The knowledge obtained from the present study, on the conditions to convert the scrambled species, could provide useful clues for a rational design for snake venom cardiotoxins with potential therapeutic applications.

Animals↗
PubMed1998

Events in the kinetic folding pathway of a small, all beta-sheet protein.

The folding of cardiotoxin analogue III (CTX III), a small (60 amino acids), all beta-sheet protein from the venom of the Taiwan Cobra (Naja naja atra) is here investigated. The folding kinetics is monitored by using a variety of techniques such as NMR, fluorescence, and circular dichroism spectroscopy. The folding of the protein is complete within a time scale of 200 ms. The earliest detectable event in the folding pathway of CTX III is the formation of a hydrophobic cluster, which possess strong affinity to bind to nonpolar dye such as 1-anilino-8-napthalene-sulfonic acid. Quenched-flow deuterium-hydrogen exchange experiments indicate that the segment spanning residues 51-55 along with Lys23, Ile39, Val49, Tyr51 and Val52 could constitute the "hydrophobic cluster." Folding kinetics of CTX III based on the amide-protection data reveals that the triple-stranded, antiparallel beta-sheet segment, which is located in the central core of the molecule, appears to fold faster than the double-stranded beta-sheet segment.

Amides↗
PubMed1998

Synergism between mycophenolate mofetil and cyclosporine in preventing graft-versus-host disease among lethally irradiated dogs given DLA-nonidentical unrelated marrow grafts.

Mycophenolate mofetil (MMF) was evaluated either alone or combined with cyclosporine (CSP) for preventing graft-versus-host disease (GVHD) in dogs given 9.2 Gy total body irradiation and DLA-nonidentical unrelated marrow grafts. Marrow autograft studies showed gut toxicity as limiting MMF side effects. Four groups were studied for GVHD prevention: six dogs in group 1 received MMF 10 mg/kg twice daily subcutaneously (SC) on days 0 to 27. They died between 8 to 28 days from infection or GVHD; survival was better than that of 72 controls given no immunosuppression (P = .04), but not different from 19 dogs given CSP. Four dogs in group 2 received MMF as described, along with CSP at 10 to 15 mg/kg twice daily on days 0 to 27. They died at 6 to 98 days from CSP-associated toxicity, weight loss, or infection. Nine dogs in group 3 received MMF SC twice daily 6 mg/kg/d for 3 days, followed by 10 mg/kg twice daily until day 27, along with CSP as described; four died between 7 to 106 days with intussusception, infection, or GVHD, and five became long-term survivors. Six dogs in group 4 received shortened MMF (21 days) and reduced doses of CSP given through day 100. Three died with GVHD or infection between days 38 to 119, and three became long-term survivors. Results support the notion of synergism between MMF and CSP, as evidenced by stable graft-host tolerance in greater than 50% of dogs.

Animals↗
PubMed1998

Main-chain dynamics of cardiotoxin II from Taiwan cobra (Naja naja atra) as studied by carbon-13 NMR at natural abundance: delineation of the role of functionally important residues.

Cardiotoxin analogue II (CTX II) is an all beta-sheet, small molecular mass (6.8 kDa), basic protein possessing a wide array of biological properties. Nearly complete assignment of the protonated carbon resonances has been achieved by heteronuclear NMR experiments. The study shows that the correlation between the carbon-13 chemical shifts and CTX II structure is good in general, but interesting deviations are also noticed. To characterize the internal dynamics of CTX II, longitudinal, transverse relaxation rates and heteronuclear 13C{1H} NOEs were measured for alpha-carbons at natural abundance by two-dimensional NMR spectroscopy. Relaxation measurements were obtained in a 14.1 T spectrometer for 50 residues, which are evenly spread along the CTX II polypeptide chain. Except for five alpha-carbons, all data were analyzed from a simple two-parameter spectral density function using the model free approach of Lipari and Szabo. The microdynamical parameters (S2, taue, and Rex) were calculated with an overall rotational correlation time (taum) for the protein of 4.8 ns. For most residues, the alpha-carbons exhibit fast (taue < 30 ps) restricted libration motions (S2 = 0.79-0.89). The present study reveals that the functionally important residues located at the tips of the three loops are flexible, and the flexibility of residues in this region could be important in the binding of cardiotoxins to their putative "receptors" which are postulated to be located on the erythrocyte membrane. In addition, the results obtained in the present study support the earlier predictions on the relative role of the lysine residues in the erythrocyte lytic activity of cardiotoxins.

Amino Acid Sequence↗
PubMed1998

Insights into the origins of binding and the recognition properties of molecularly imprinted polymers prepared using an amide as the hydrogen-bonding functional group.

Molecularly imprinted polymers (MIPs) prepared using an amide hydrogen-bonding functional monomer (acrylamide) exhibited efficient enantiomeric recognition properties in both organic and aqueous media in the HPLC mode. The results indicate that the amide functional groups formed strong hydrogen-bonding interactions with the template molecule, and specific recognition sites were created within the polymer matrix during the imprinting process. When Boc-L-Trp was used as the template, an MIP prepared in a polar organic solvent (acetonitrile) using acrylamide as the functional monomer showed better enantiomeric recognition of Boc-Trp than the MIPs prepared in the same solvent using an acidic (methacrylic acid) or a basic (2-vinylpyridine) functional monomer or a combination of an acidic and a basic functional monomer (methacrylic acid + 2-vinylpyridine). Our results indicate that in organic media the degree of retention of the sample molecule on the imprinted polymer was controlled by hydrogen-bonding interactions between the sample molecule and the polymer, while in aqueous media it was determined to a considerable extent by hydrophobic interactions. In both media the shape, size and the nature of the hydrogen-bonding groups of the sample molecules were all important factors in determining the enantiomeric and substrate selectivity. In the aqueous media, however, the hydrophobicity of the sample molecules was also found to play an important role.

Amides↗
PubMed1998

Pictorial review: Radiological diagnosis of duodenal abnormalities.

This article depicts the radiological findings of many common gastrointestinal entities. Specifically, examples of disease processes that affect the stomach, gall bladder, small intestine, pancreas and colon are shown. In most cases there is correlation between ultrasound, computed tomography (CT) and fluoroscopic imaging. The major emphasis of the article, however, is to demonstrate classic barium imaging of a large number of gastrointestinal disease processes.

Barium Sulfate↗
PubMed1998

Rectification nonlinearity in cortical end-stopped perceptive fields.

End-stopped perceptive fields associated with line targets were demonstrated previously with length and width Westheimer functions. In this study we investigated rectifying non-linearity in these perceptive fields to examine whether they directly reflect the organization of cortical receptive fields. Specifically, we reversed the polarity of parts of the background field associated with a specific perceptive field sub-region and examined threshold changes in corresponding length or width Westheimer functions. Results showed full-wave rectification in end-stopping and half-wave rectification in center summation and flank-inhibition preceding linear summation in end-stopped perceptive fields. Half-wave rectification in center summation and surround-inhibition preceding linear summation was also found in circular perceptive fields associated with spot targets. These results are inconsistent with direct links between perceptive fields and cortical receptive fields. Rather they suggest that these perceptive fields are likely the second-order fields formed by pooled non-linearly rectified outputs from cortical receptive fields.

Adult↗
PubMed1998

Fetal ethanol effects on benzodiazepine sensitivity measured by behavior on the elevated plus-maze.

Rodents prenatally exposed to ethanol demonstrate altered behavioral and hormonal responses to stressful environments. Prenatal ethanol exposure may also have long-term effects on the offspring's GABAergic system. Using the elevated plus-maze, the present study examined the sensitivity of adult Sprague-Dawley rat offspring from prenatal ethanol (E), pair-fed (PF) and ad lib-fed control (C) conditions to the effects of benzodiazepine (BZD) on plus-maze behavior and corticosterone (CORT) responses. At 60-90 days of age, E, PF, and C males and females were injected subcutaneously with either BZD or saline. Twenty minutes later animals were placed in an open field (OF) for a 5-min test and then on the plus-maze for a 5 min test; behaviors were recorded during testing and blood samples collected at the end of testing for CORT determinations. Overall, sex differences were observed in both OF and plus-maze behaviors. Females showed more ambulation and rearing in the OF than males, and exhibited increased exploratory behaviors and decreased fear-related behaviors compared to males on the plus-maze. Following BZD treatment, both males and females exhibited increased time on open arms, increased open arm entries, and decreased time on closed arms compared to saline-treated males and females, regardless of prenatal treatment. These differences did not appear to be due to altered activity levels, as BZD treatment had no effect on total ambulation in the OF. Importantly, although no significant differences in plus-maze behaviors were found among saline-injected E, PF, and C males or females. BZD treatment differentially affected E males and females compared to their PF and C counterparts. Both E males and females treated with BZD spent increased time on open arms and decreased time on closed arms compared to their PF and C counterparts, suggesting decreased fear. Further, BZD-treated E males exhibited decreased open and closed arm entries, spent significantly more time in the central area, and had lower CORT levels, another index of fear or stress, compared to BZD-treated PF and C males. These data support and extend previous work demonstrating that the plus-maze provides a reliable measure of anxiety/fear, and that plus-maze behavior is sensitive to anxiolytic agents such as BZD. Furthermore, these data suggest that prenatal ethanol exposure may alter sensitivity to the effects of BZD on plus-maze behavior and CORT responsiveness, and may do so differentially in male and females offspring.

Animals↗
PubMed1998

Ultrasound-guided interventional procedures in splenic abscesses.

The results of ultrasound (US)-guided interventional procedures over a period of 12 years in 21 consecutive patients with splenic abscess were reviewed. The interventional procedures were done with 21- or 18-gauge needles for aspiration of relatively small abscesses (< 3.5 cm) in eight patients and with an 8.3-9.0 French pigtail catheter for continuous drainage in 13 patients with larger abscesses (> or = 3.5 cm). In some patients, multiple abscesses were treated separately according to their various sizes. More than one catheterization were done in three patients because of detached catheter or recurrent abscesses. The interventional procedures were followed by at least eight weeks of appropriate antibiotic therapy. Only one patient had the complication of minimal subcapsular hematoma which needed no further treatment. All the patients had uneventful clinical courses. US-guided interventional procedure proved to be a treatment-of-choice for splenic abscess, and may avoid splenectomy by conserving the spleen.

Abscess↗
PubMed1998

A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogenesis.

We report here that neuregulin (NRG) isoforms with a conserved cysteine-rich domain (CRD) in their N terminus regulate expression of nicotinic acetylcholine receptors (nAChRs) at developing interneuronal synapses and report the isolation of transmembrane NRG isoforms with this CRD within the N-terminal portion. CRD-NRG mRNA and immunoreactive protein are detected early in developing presynaptic (visceral motor) neurons. The levels of expression of CRD-NRG peak prior to the formation of synapses with their postsynaptic partners, the ganglionic sympathetic neurons. Recombinant CRD-NRG mimics the effects of presynaptic input on target neurons. Functional deletion of CRD-NRG from presynaptic neurons abolishes the upregulation of nAChR expression induced by input-derived soluble material. Thus, CRD-NRG appears to be both a necessary and a sufficient signal for the control of neuronal nAChR expression during synaptogenesis.

Acetylcholine↗
PubMed1998

Quantitative structure-activity relationships on 5-substituted terbenzimidazoles as topoisomerase I poisons and antitumor agents.

Several 5-substituted terbenzimidazoles were synthesized and evaluated as mammalian topoisomerase I poisons and for cytotoxicity against a human lymphoblastoma cell line, RPMI-8402. No correlation was observed between topoisomerase I poisoning activity and the Hansch pi value or the sigma meta and sigma para values associated with each substituent. These data suggest that electronic effects and relative lipophilicity of substituents at the 5-position of these terbenzimidazoles do not have a significant effect upon intrinsic topoisomerase I poisoning activity. There was, however, a good correlation between the relative pi values for the various substituents evaluated and cytotoxic activity. Experimentally determined log P values did not correlate well with either cytotoxicity or pi values. Capacity factors (log k') as determined by high pressure liquid chromatography did correlate well with the pi values of varied substituents and cytotoxicity. These data indicate that the relative lipophilic activity of substituents at the 5-position of these terbenzimidazoles can strongly influence relative cytotoxic activity.

Antineoplastic Agents↗
PubMed1998

The biologic effects of growth factor-toxin conjugates in models of vascular injury depend on dose, mode of delivery, and animal species.

Toxin-conjugates, complexes designed from the fusion of tissue toxins and pathology-specific ligands, offer the potential for targeted cytotoxic therapy. Some have postulated that the recurrent failure of these conjugates to exhibit benefit in animal models of vascular injury arose because the timing and frequency of conjugate delivery were insufficient to meet the demands of the arterial wall. Previous data suggest that increasingly frequent dosing would lead to superior inhibition of intimal hyperplasia. We now report on the biological effects of the controlled release of a recombinant conjugate of basic fibroblast growth factor (bFGF) and the plant toxin saporin (SAP), bFGF-SAP. Alginate/heparin-Sepharose microspheres and films were designed as drug carriers to control release the bFGF-SAP conjugate or bFGF alone in small doses. When bFGF-SAP-incorporated microspheres or films were implanted adjacent to balloon angioplastied porcine carotid arteries, the controlled release of bFGF-SAP over the four-week study stimulated rather than inhibited hyperplasia. When these same devices were used in cell culture, unexpected findings were produced. bFGF-SAP reduced in vitro bovine vascular smooth muscle cell growth at high concentrations (1-10 microgram/mL) but increased smooth muscle cell growth at lower concentrations (up to 1 microgram/mL). Microsphere controlled-released bFGF-SAP ( approximately 60 ng/mL over 4 days) stimulated the growth of smooth muscle cells more than any of the tested bolus applications of the conjugate. These data provide cause to reconsider our acceptance of controlled release technology as the answer to all forms of drug delivery problems, and to apply more rigorous means of matching the kinetics of drug delivery to the kinetics of the vascular response to injury.

Angioplasty↗
PubMed1998

Expression of Th1/Th2 cytokine mRNA in peritoneal exudative polymorphonuclear neutrophils and their effects on mononuclear cell Th1/Th2 cytokine production in MRL-lpr/lpr mice.

Peritoneal exudative polymorphonuclear neutrophils (PEC-PMN) and mononuclear cells (PEC-MNC) were obtained from normal BALB/c and from autoimmune MRL-lpr/lpr mice (lpr) with different disease severities. The spontaneous and mitogen-stimulated expression of T-helper lymphocyte type-1 (Th1) [represented by interferon-gamma (IFN-gamma) and interleukin (IL-2)] and T-helper lymphocyte type-2 (Th2) (represented by IL-4 and IL-10) cytokine mRNA in these cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). The production of these cytokines was measured by enzyme-linked immunosorbent assay (ELISA). We found that the spontaneous expression of Th1/Th2 cytokine mRNA in PEC-PMN from autoimmune mice was progressively increased in parallel with disease severity but was not changed by lipopolysaccharide (LPS) stimulation. By contrast, spontaneous expression of Th1/Th2 cytokine mRNA in PEC-MNC from these mice was progressively decreased in parallel with disease severity but retained the responsiveness to phytohaemagglutinin (PHA) stimulation. To determine the effect of PEC-PMN on Th1/Th2 cytokine production by PEC-MNC, autologous PEC-PMN and PEC-MNC were co-cultured at MNC:PMN ratios of 5:0, 4:1, 3:2, 2:3, 1:4 and 0:5 with PHA stimulation for 24 hr. The production of cytokines at each ratio was compared with the expected value, by calculation. We found that PEC-PMN from autoimmune mice progressively suppressed the production of IL-4, IL-10 and IFN-gamma whereas the production of IL-2 was enhanced by autologous MNC in parallel with disease severity. These results suggest that a reciprocal relationship exists in the expression of Th1/Th2 cytokine mRNA between PEC-PMN and PEC-MNC in lpr mice in parallel with disease severity. Autoimmune PEC-PMN can exert significant modulatory effects on Th1/Th2 cytokine production by autologous MNC in stimulation.

Animals↗
PubMed1998

The role of acetic acid in the prevention of salt-induced aggregation of snake venom cardiotoxins.

Snake venom cardiotoxins (CTXs) exhibit a strong tendency to aggregate upon desalting and hence it is extremely difficult to prepare salt-free cardiotoxin(s). In the present study, we describe a new method for preparation of salt-free CTX based on dialysis against acetic acid. Based on experimental observation and the three dimensional solution structure of cardiotoxin analogue III from the Taiwan cobra (Naja naja atra), a molecular mechanism for the prevention of aggregation of cardiotoxins by acetic acid is discussed. In our opinion, the results obtained in the present study would pave way for elucidating the structural basis for the broad spectrum of biological activities exhibited by snake venom cardiotoxins.

Acetic Acid↗
PubMed1998

The role of proline in the prevention of aggregation during protein folding in vitro.

Proline effectively inhibits protein aggregation during the refolding of bovine carbonic anhydrase. Other osmolytes used such as glycine and ethylene glycol fail to exhibit the 'aggregation-blockade' role shown by proline. Results of viscosity and ANS fluorescence (1-anilino-8-naphthalene sulphonic acid) experiments suggest that proline at high concentrations forms an ordered supramolecular assembly. Based on these results, it is proposed that proline behaves as a protein folding chaperone due to the formation of an ordered, amphipathic supramolecular assembly. To our knowledge, this is the first report wherein proline is proposed as a protein folding aid.

Anilino Naphthalenesulfonates↗