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Biomedical subjects

C F Liu

Publications and source records attributed to C F Liu.

At least 19 recordsLinked to original sources
PubMed2000

A comparison of folding techniques in the chemical synthesis of the epidermal growth factor-like domain in neu differentiation factor alpha/beta.

The 52-residue alpha/beta chimera of the epidermal growth factor-like domain in neu differentiation factor (NDFealpha/beta) has been synthesized and folded to form a three disulfide bridge (Cys182-Cys196, Cys190-Cys210, Cys212-Cys221) containing peptide. We investigated two general strategies for the formation of the intramolecular disulfide bridges including, the single-step approach, which used fully deprotected and reduced peptide, and a sequential approach that relied on orthogonal cysteine protection in which specific pairs are excluded from the first oxidation step. Because there are 15 possible disulfide bridge arrangements in a peptide with six cysteines, the one-step approach may not always provide the desired disulfide pairing. Here, we compare the single-step approach with a systematic evaluation of the sequential approach. We employed the acetamidomethyl group to protect each pair of cysteines involved in disulfide bridges, i.e. Cys182 to Cys196, Cys190 to Cys210 and Cys212 to Cys221. This reduced the number of possible disulfide patterns from 15 to three in the first folding step. We compared the efficiencies of folding for each protected pair using RP-HPLC, mapped the disulfide connectivity of the predominant product and then formed the final disulfide from the partially folded intermediate via 12 oxidation. Only the peptide having the Cys182-Cys196 pair blocked with acetamidomethyl forms the desired disulfide isomer (Cys190-Cys210/Cys212-Cys221) as a single homogeneous product. By optimizing both approaches, as well as other steps in the synthesis, we can now rapidly provide large-scale syntheses of NDFealpha/beta and other novel EGF-like peptides.

Amino Acid Sequence↗
PubMed2000

Cardiovascular manifestations of pheochromocytoma.

Pheochromocytomas are rare tumors that originate in chromaffin tissue and produce their distant variant effects by secretion of catecholamines, tending to mislead the emergency physicians to a wrong diagnosis. Therefore, we analyze the clinical cardiovascular manifestations in patients with pheochromocytoma to improve the diagnostic ability of the emergency physicians. All patients presenting to the Chang Gung Memorial Hospital between January 1993 and December 1997 with a final diagnosis of pheochromocytoma had their charts reviewed. The data of 25 patients including age, sex, adrenergic stimulation presentations, electrocardiographic changes, location of the tumor, and complications were analyzed. Hypertension was the most important major manifestation and fluctuation of blood pressure drew our attention to the possibility of pheochromocytoma. Six patients had abnormal electrocardiographic ST-T segment changes. Five of them had chest pain which prompted them to undergo coronary angiography before surgery, because acute coronary syndrome (unstable angina and acute myocardial infarction) was suspected initially. However, all of them turned out to have normal coronary arteries. Right-sided pheochromocytoma was found in three of these five patients. We should maintain high index of suspicion for pheochromocytoma in patients presenting with chest pain, fluctuating blood pressure, and ischemic electrocardiogram (ECG) changes despite any typical isoenzyme changes. Pheochromocytoma should also be included in the differential diagnosis of acute coronary syndrome because acute catecholamine secretion may induce chest pain and abnormal ECG changes mimicking an ischemic episode. The right-sided pheochromocytoma may present more striking electrocardiographic abnormalities and clinical manifestations.

Adolescent↗
PubMed1999

Outcomes for Medicaid beneficiaries with schizophrenia under a prepaid mental health carve-out.

This study examines the impact of a mental health carve-out program in Utah on mental health status of Medicaid beneficiaries with schizophrenia. Three community mental health centers contracted to provide mental health care for all Medicaid beneficiaries in their service areas under managed care arrangements, while beneficiaries in the remainder of the state remained under traditional Medicaid. A pre-post evaluation was utilized, with a contemporaneous control group of Utah Medicaid beneficiaries with schizophrenia under traditional Medicaid. From 1991 to 1994, the average beneficiary's mental health status improved, but the improvement was less under the carve-out program than under traditional fee-for-service Medicaid. The difference was the greatest for beneficiaries with the worst mental health status at baseline, with effects growing over time. Medicaid beneficiaries with schizophrenia experienced less improvement in mental health status under a carve-out arrangement for mental health care compared to what would have happened under traditional Medicaid.

Adult↗
PubMed1999

Patterns of outpatient use of mental health services for Medicaid beneficiaries under a prepaid mental health carve-out.

This study examines the impact of a mental health carve-out, the Utah Prepaid Mental Health Plan (UPMHP), on use of outpatient mental health services by Medicaid beneficiaries with schizophrenia. Data were collected through interviews with the same group of Medicaid schizophrenic beneficiaries. A pre/post comparison with a contemporaneous control group examined the impact of the program on type of outpatient services used by beneficiaries. The results indicate a greater reliance on medically-oriented outpatient mental health services in treatment of beneficiaries under the UPMHP. Medicaid beneficiaries with schizophrenia in the UPMHP group received relatively fewer day treatment visits, but relatively more medication visits and individual therapy visits over the first 3 1/2 years of the program.

Adult↗
PubMed1998

Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr.

The HIV-1 protein Vpr is critical for a number of viral functions including a unique ability to arrest T-cells at a G2/M checkpoint and induce subsequent apoptosis. It has been shown to interact specifically with the second UBA (ubiquitin associated) domain found in the DNA repair protein HHR23A, a highly evolutionarily conserved protein. This domain is a commonly occurring sequence motif in some members of the ubiquitination pathway, UV excision repair proteins, and certain protein kinases. The three dimensional structure of the UBA domain, determined by NMR spectroscopy, is presented. The protein domain forms a compact three-helix bundle. One side of the protein has a hydrophobic surface that is the most likely Vpr target site.

Amino Acid Sequence↗
PubMed1998

The demand for health insurance by employees in a voluntary small group insurance program.

OBJECTIVES: This study examined the decisions of small group employees to enroll in prepaid plans offered through Healthcare Group of Arizona (HCGA), a state-sponsored and state-administered voluntary insurance program. METHODS: The study population included 653 potential employee enrollees who were offered the option of two health plans between January 1993 and June 1993, with 447 enrolling in one of the two plans. Data sources included two telephone surveys, HCGA administrative files, and enrollment application forms. RESULTS: The estimates of adjusted price elasticity were in the range of -0.12 to -0.24 for employees with prior insurance and were in the range of -0.42 to -0.51 for employees without prior insurance. The likelihood of enrolling in HCGA increased with log(income) and decreased with log(income) squared. The average income elasticity across income groups was 0.12. CONCLUSIONS: The results indicate that small group employees without prior insurance were more sensitive to the price of health insurance than those with prior insurance. Healthcare Group of Arizona health plans may have been viewed as inferior goods by high income employees possible because of their association with the Medicaid program.

Adult↗
PubMed1998

Lanthionine macrocyclization by in situ activation of serine.

The present report details a straightforward, solid-phase approach to cyclolanthionine peptides. After stepwise assembly of the linear sequence and transformation of a single exposed serine to bromoalanine using P(Ph)3/CBr4, the detritilation of a cysteine side-chain sets the stage for a base-promoted macrocyclization. The entire procedure can be carried out in a solid-phase vessel using conventional 9-fluorenylmethyloxycarbonyl/tert-butyl-based chemistry and is amenable to automated format. The utility of this novel procedure is demonstrated by the synthesis of two previously reported lanthionine-containing cyclic peptides.

Alanine↗
PubMed1997

The early experience of a voluntary small group insurance program utilizing managed care plans.

HealthCare Group of Arizona (HCGA), a state-sponsored, voluntary health insurance purchasing program offering prepaid health plans to small businesses, became operational in 1988. This article summarizes the results from a wide-ranging evaluation of that program and discusses their implications. In general, enrollees were satisfied with their experience in their plans. HCGA did not appear to attract an adverse mix of health risks, and service utilization rates were consistent with HMO industry averages. However, these findings varied across health plans and the marketing approaches they adopted. Enrollment growth in HCGA has been steady, but premium subsidies may be necessary if HCGA is to substantially increase its enrollment of low-wage, uninsured workers.

Adolescent↗
PubMed1996

Microcirculatory vasoconstrictor response: relationship with vital capacity and smoking.

Vasoconstrictor response (VR) induced by inspiratory gasp exhibited a strong positive correlation with vital capacity (VC) which reflects the magnitude of the input stimulus for VR (Lau et al., Clin. Sci. 89:233-237, 1995). Whether a stoichiometric relationship existed between VC and VR is not known. We examined this question in two studies by determining VC and microcirculatory blood flow with laser Doppler flowmetry in healthy subjects. We first studied 40 non-smokers of different gender and age and found that the variation in VR cannot be eliminated by normalization with VC. In the second study we examined 10 young male smokers as well as matched non-smokers of identical VC, we found that smokers had reduced VR. Taking together, the present studies demonstrated that vasoconstrictor response (VR) was not determined by vital capacity alone and that smoking adversely affected VR in the absence of altered VC.

Adult↗
PubMed1996

Income, health status, and insurance coverage of small group employees in a voluntary purchasing arrangement.

The ongoing health care reform discussion has highlighted the problems of insuring small group employees. Several state and private initiatives have attempted to address some of these problems through the formation of voluntary small group purchasing arrangements. This article uses data from one such initiative, Health Care Group of Arizona (HCGA), to describe the income, health status, and prior insurance of small group employees who enrolled in prepaid health plans through HCGA. It also compares employee enrollees to nonenrollees along these dimensions. The findings suggest that HCGA enrollees had relatively low incomes and that about three-quarters were without health insurance prior to enrollment. Higher income employee enrollees were more likely to report health conditions at enrollment even after controlling for other factors including age. Enrollees were less likely than nonenrollees to have prior health insurance but were more likely to be drawn from lower income groups and to report recent health conditions.

Adolescent↗
PubMed1995

Peptide synthesis using unprotected peptides through orthogonal coupling methods.

We describe an approach to the synthesis of peptides from segments bearing no protecting groups through an orthogonal coupling method to capture the acyl segment as a thioester that then undergoes an intramolecular acyl transfer to the amine component with formation of a peptide bond. Two orthogonal coupling methods to give the covalent ester intermediate were achieved by either a thiol-thioester exchange mediated by a trialkylphosphine and an alkylthiol or a thioesterification by C alpha-thiocarboxylic acid reacting with a beta-bromo amino acid. With this approach, unprotected segments ranging from 4 to 37 residues were coupled to aqueous solution to give free peptides up to 54 residues long with high efficiency.

Acylation↗
PubMed1995

Chronic intracerebroventricular administration of morphine down-regulates spinal adenosine A1 receptors in rats.

Previous studies from our laboratory have shown that systemic chronic morphine treatment causes down-regulation of spinal adenosine A1 receptors in rats. In this study, we further investigated whether supraspinal morphine treatment causes this effect. Adult male Sprague-Dawley rats were rendered tolerant to morphine by multiple intracerebroventricular (i.c.v.) injections for 2 or 4 days. Adenosine A1 receptor binding activities were measured with [3H]cyclohexyladenosine in the spinal cord and midbrain. A significant decrease in [3H]cyclohexyladenosine binding was found in the spinal cord but not in the midbrain region after 2 or 4 days of chronic i.c.v. morphine treatment. A decrease in the number of binding sites (Bmax) with no change in the affinity (Kd) of the ligand for the adenosine A1 receptor was observed. These results suggest that supraspinal morphine administration could cause the down-regulation of spinal adenosine A1 receptors and this may play a role in the mechanism of morphine tolerance.

Adenosine↗
PubMed1995

Cutaneous vasoconstrictor response induced by inspiratory gasp in relation to sex and age.

1. Vasoconstrictor responses to inspiratory gasp were determined in fingertip skin by laser Doppler flowmetry in relation to age and gender of healthy adults. Variations of the responses were examined together with variations in body mass index and vital capacity. 2. In the absence of any significant difference in the baseline blood flow, the index of vasoconstrictor response (per cent change) induced by inspiratory gasp was higher in young males than in young females (71.4% versus 59.4%; P < 0.05), and in the same direction as the change in vital capacity determined in the same laboratory setting. Similar parallel differences in the indexes of vasoconstrictor response and vital capacity existed between young and middle-aged males, suggesting that the differences observed were not due to gender or age per se. 3. Strong positive correlations between the index of the vasoconstrictor response and vital capacity in the same subject were found when young males and females were pooled together and when young and middle-aged males were pooled together. Furthermore, after graded inspiratory gasp, graded vasoconstrictor response was observed in the same subject, indicating a close relationship between the depth of inspiration (magnitude of stimulus) and the index of the vasoconstrictor response (reactivity). 4. We concluded that the index of the vasoconstrictor response induced by inspiratory gasp depends significantly on the magnitude of the vital capacity. These results provide a new approach for quantifying dynamic changes in skin blood flow and raise caveats about comparing differences in neurovascular functions using single measurements of vasoconstrictor response induced by inspiratory gasp as an index.

Adult↗
PubMed1995

Specificity and formation of unusual amino acids of an amide ligation strategy for unprotected peptides.

An important step in the recently developed ligation strategy known as domain ligation strategy to link unprotected peptide segments without activation is the ring formation between the C-terminal ester aldehyde and the N-terminal amino acid bearing a beta-thiol or beta-hydroxide. A new method was developed to define the specificity of this reaction using a dye-labeled alanyl ester aldehyde to react with libraries of 400 dipeptides which contained all dipeptide combinations of the 20 genetically coded amino acids. Three different ester aldehydes of the dye-labeled alanine: alpha-formylmethyl (FM), beta-formylethyl (FE), and beta,beta,beta-dimethyl and formylethyl esters (DFE), were examined. The DFE ester was overly hindered and reacted with N-terminal Cys dipeptides (Cys-X). Interestingly, it also reacted slowly with the sequences of X-Gly where Gly was the second amino acid and the X-Gly amide bond participated in the ring formation. Although the FE ester reacted similarly as the FM ester in the ring formation, the subsequent O,N-acyl transfer was at least 30-fold slower than those of the FM-ester. The FM alpha-formyl methyl ester was the most suitable ester and was reactive with dipeptides of six N-terminal amino acids: Cys, Thr, Trp, Ser, His and Asn. The order and extent of their reactivity were highly dependent on pH, solvent and neighboring participation by the adjacent amino acid. In general, they could be divided into three categories. (1) N-Terminal Cys and Thr were the most reactive.(ABSTRACT TRUNCATED AT 250 WORDS)

Amides↗
PubMed1994

Peptide segment ligation strategy without use of protecting groups.

We describe the concept and the verification of a chemical ligation approach to the synthesis of proteins using peptide segments with no protecting groups and no activation of the C-terminal alpha-carboxyl group. This approach consists of three steps: (i) aldehyde introduction, in which a masked glycolaldehyde ester is linked to the carboxyl terminus of an unprotected peptide by reverse proteolysis; (ii) ring formation, in which the unmasked aldehyde reacts with the N-terminal alpha-amino group of the second unprotected peptide containing either a cysteine or a threonine residue to form a thiazolidine or oxazolidine ring at an acidic pH; and (iii) rearrangement in which O-acyl ester linkage is transferred to N-acyl amide linkage to form a peptide bond with a pseudoproline structure at higher pH. The feasibility of this scheme was verified by a model study on small compounds and its potential was demonstrated by the synthesis of a 50-residue epidermal growth factor-like peptide containing a preformed disulfide bond.

Amino Acid Sequence↗
PubMed1994

Prospecting for customers in the small employer market: the experience of Arizona Health Care Group.

The findings of this study provide an interesting profile of the small employer "prospects" for prepaid health plans, where a prospect is defined as an employer that responds to a mass mailing effort with a request for information and further contact. About 60% of these prospects already have insurance, with 40% having group insurance. Therefore, a substantial portion of prospects are seeking to replace their existing health benefit package with a different one. Of those who do not offer existing insurance, the most common reason is that it is "too expensive" or the employer is "not profitable." A very small proportion do not offer insurance because they do not qualify for it due to medical underwriting considerations. Prospects tend to be larger than non-prospects in terms of sales, but employ lower wage employees, on average. About half of prospects are in service industries, a proportion typical of small employers in general. Somewhat surprisingly, most prospects have been in operation for over five years. They are not new firms attempting to establish their benefit packages. This is consistent with the findings on gross sales, suggesting that some maturity is necessary before an employer considers offering group health insurance as a benefit. The prepaid plans in this study also appeared to target established employers for their marketing efforts. In responding to questions about their attitudes towards health insurance, over one-quarter of prospects indicated that they would be unwilling to offer insurance at rates so low that they would not normally apply to the coverages offered by prepaid plans. Thus, although they were "prospects" by the study's definition, they were unlikely to eventually contract with prepaid plans. Those prospects that had offered insurance previously, but had discontinued it, tended to cite premium increases as the reason. This suggests that prospects among small employers are likely to be very price sensitive, and that further prescreening of prospects by phone, during which premium levels are discussed, might be cost-effective in following up leads from mass mailings. The study data also suggest the importance of quick follow-up for mass mailing leads, as the drop-off in recall and interest appears to be substantial. About half of the prospects interviewed stated that they were unaware of AHCG, although they or someone in their business had returned a mailer requesting more information. In addition to their implications for marketing to small employers, the results of the study appear to have broader policy implications as well.(ABSTRACT TRUNCATED AT 400 WORDS)

Arizona↗