Biomedical subjects

C C Lin

Publications and source records attributed to C C Lin.

At least 145 records · Page 8Linked to original sources

PubMed1998

[Self-care behaviors, self-efficacy, and social support effect on the glycemic control of patients newly diagnosed with non-insulin-dependent diabetes mellitus].

The purpose of this study was to explore the glycemic control and influencing factors in outpatients newly diagnosed with non-insulin-dependent diabetes mellitus (NIDDM). By purposeful sampling, data were collected from 130 outpatients with NIDDM at one medical center in Kaohsiung. The results indicated: (1) the mean value for HbA1C was 7.12%; and 63.1% of the patients belonged to moderate to well controlled group; (2) male patient's HbA1C value was significantly lower than female patient's; patients with no religious belief also had a lower HbA1C value than patients with a religious background; (3) there were strongly negative correlations between self-care behaviors, social support, and self-efficacy and HbA1C; (4) using a multiple stepwise regression analysis, religious belief and self-care behaviors were found to explain 10.9% variance of HbA1C level. The results of this study could be used as a reference for diabetes health education program.

Adult↗

PubMed1997

DK phocomelia phenotype (von Voss-Cherstvoy syndrome) caused by somatic mosaicism for del(13q).

DK phocomelia (von Voss-Cherstvoy syndrome) is a rare condition characterized by radial ray defects, occipital encephalocoele, and urogenital abnormalities. Lubinsky et al. [1994: Am J Med Genet 52:272-278] pointed out similarities between this and the del(13q) syndrome. To date, all reported cases of DK phocomelia have been apparently normal chromosomally. We report on a case of DK phocomelia in which the proposita had normal lymphocyte chromosomes, but was mosaic in fibroblasts for del(13)(q12). Fibroblast chromosomes studies on other cases of DK phocomelia have not been reported: this raises the possibility that some cases of DK phocomelia may be somatic mosaics for del(13)(q12).

Adult↗

PubMed1997

Structure-activity relationship of 3-substituted N-(pyridinylacetyl)-4- (8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene )- piperidine inhibitors of farnesyl-protein transferase: design and synthesis of in vivo active antitumor compounds.

Novel tricyclic Ras farnesyl-protein transferase (FPT) inhibitors are described. A comprehensive structure-activity relationship (SAR) study of compounds arising from substitution at the 3-position of the tricyclic pyridine ring system has been explored. In the case of halogens, the chloro, bromo, and iodo analogues 19, 22, and 28 were found to be equipotent. However, the fluoro analogue 17 was an order of magnitude less active. Whereas a small alkyl substituent such as a methyl group resulted in a very potent FPT inhibitor (SCH 56580), introduction of bulky substituents such as tert-butyl, compound 33, or a phenyl group, compound 29, resulted in inactive FPT inhibitors. Polar groups at the 3-position such as amino 5, alkylamino 6, and hydroxyl 12 were less active. Whereas compound SCH 44342 did not show appreciable in vivo antitumor activity, the 3-bromo-substituted pyridyl N-oxide amide analogue 38 was a potent FPT inhibitor that reduced tumor growth by 81% when administered q.i.d. at 50 mpk and 52% at 10 mpk. These compounds are nonpeptidic and do not contain sulfhydryl groups. They selectively inhibit FPT and not geranylgeranyl-protein transferase-1 (GGPT-1). They also inhibit H-Ras processing in COS monkey kidney cells and soft agar growth of Ras-transformed cells.

3T3 Cells↗

PubMed1997

High-performance liquid chromatographic determination and stability of 5-(3-methyltriazen-1-yl)-imidazo-4-carboximide, the biologically active product of the antitumor agent temozolomide, in human plasma.

5-(3-Methyltriazen-1-yl)-imidazo-4-carboximide (MTIC) is a highly unstable compound which is believed to be the biologically active degradation product of the antitumor agent temozolomide. An HPLC method has been developed and validated for the analysis of MTIC in human plasma. Because of the instability of MTIC, sample processing was kept to minimal. The method involved precipitation of plasma protein with methanol followed by analysis of the supernatant using reversed-phase column and UV detection at 316 nm. The linearity (r>0.99), precision (C.V.<9%) and accuracy (bias<5%) were satisfactory. The lower limit of quantitation (LOQ) was 10 ng/ml. The recovery of MTIC and internal standard was > or = 86.7%. MTIC was stable in plasma though three freeze-thaw cycles, and was stable at 4 degrees C for 1 h and at -80 degrees C for at least 70 days. MTIC may be unstable at 10 degrees C in processed samples; therefore, samples were placed in the autosampler (10 degrees C) immediately prior to injection. By using this analytical method, MTIC was quantified in plasma of cancer patients (n=12) within 0.25-12 h after oral administration of temozolomide at 150 mg/m2. The mean maximum plasma concentration (Cmax) was 211 ng/ml which was observed at a mean Tmax of 1.88 h post dose. MTIC disappeared rapidly from plasma with an apparent in vivo half-life (t1/2) of 1.9 h similar to that of temozolomide. Following in vitro incubation of MTIC in human plasma at 25 degrees C, MTIC disappearance was bioexponential with estimated t1/2 values of 25 and 60 min for the first and second phases, respectively. Therefore, the elimination t1/2 of MTIC in human in vivo (1.9 h) was controlled by the rate of its formation from temozolomide.

Administration, Oral↗

PubMed1997

Loss of imprinting and overexpression of IGF2 gene in gastric adenocarcinoma.

Both insulin-like growth factor II (IGF2) and H19 gene are located on chromosome 11p15.5 in close vicinity to each other, and are imprinted on different parental alleles. Although the exact mechanism remains unclear, loss of imprinting (LOI) leading to the biallelic expression of IGF2 and H19 genes has recently been reported in a variety of tumors. To study the role of IGF2 and H19 genes in gastric carcinogenesis, the LOI and loss of heterozygosity (LOH) status of these two genes were determined in 70 patients with gastric cancer. Among them, 30 patients were heterozygous for IGF2, 28 patients were heterozygous for H19, and 42 patients were heterozygous for either IGF2 or H19 gene. Among the 30 patients who were heterozygous for IGF2, one exhibited LOH (1/30, 3.3%) and 10 exhibited LOI (10/29, 34.5%). None of the 28 patients heterozygous for H19 gene had either LOH or LOI. LOI of IGF2 was more frequently found in the diffuse type (8/15, 53.3%) than the intestinal type (2/14, 14.3%, P < 0.05) gastric cancer. Five out of the six tumors with LOI of IGF2 exhibited overexpression of mRNA, but no obvious alterations of expression of H19 were noted by Northern hybridization. These data suggest that LOI leading to overexpression of IGF2 plays an important role in carcinogenesis of diffuse type gastric cancer.

Adenocarcinoma↗

PubMed1997

Cephalosporin 3'-phloroglucide esters and 7-(phloroglucidamido) cephalosporins as novel antibacterial agents.

Two series of new phloroglucide derivatives were synthesized that possessed antibacterial activities. The first series includes cephalosporin 3'-phloroglucide esters 19 and 20, which were obtained by condensation of cephalosporin 16 with bioactive phloroglucides 14 and 15, respectively. They exhibited a dual mode of antibacterial action. In comparison with cephalosporins 26 and 27, bearing an acetoxy unit at the C-3' position, the bifunctional cephalosporins 19 and 20 showed a broadened spectrum of activity. Results from the consistent valence force field (CVFF) calculations indicate that the most stable conformational isomer of phenolic acid 14, holding a cis-syn-syn geometry, possessed a cavity. It provides an ideal environment to accommodate metal ions of holoenzymes. Phenolic keto acid 15, however, possessed a trans-anti-syn conformation, which allowed chelation between metal ions and the phenolic hydroxyl groups as well as the carbonyl functionalities. Our biological results show that the cavity formed in phloroglucides plays an important role. The second series includes 7-(phloroglucidamido)cephalosporins 24 and 25, which were synthesized by condensation of cephalosporin 21 with 14 and 15, respectively. Results from the CVFF calculations indicate that cephalosporin 24 also possessed a cavity. Unlike cephalosporin 3'-phloroglucide esters 19 and 20, cephalosporins 24 and 25 were found resistant to beta-lactamases from Staphylococcus aureus 95 and Pseudomonas aeruginosa 18S-H. These new compounds, however, showed notable activities against S. aureus FDA 209P, S. aureus 95, Candida albicans, P. aeruginosa 1101-75, and P. aeruginosa 18S-H.

Anti-Bacterial Agents↗

PubMed1997

Pharmacokinetic screening for the selection of new drug discovery candidates is greatly enhanced through the use of liquid chromatography-atmospheric pressure ionization tandem mass spectrometry.

Selection of a new drug discovery candidate from a series of compounds requires a means of performing rapid analytical method development and sensitive quantitation of each drug in serum, plasma or other biological matrices. Information on serum/plasma concentration, bioavailability and half-life can often aid the discovery process by selecting those candidates with the desired pharmacokinetic parameters. In one series of farnesyl protein transferase (FPT) inhibitors, gas chromatography with nitrogen-phosphorus detection (NPD) was initially used to analyze samples from pharmacokinetic studies in mice and monkeys. Typical turnaround times using this technique approached 2-4 weeks for method development, quantitation of study samples and calculation of pharmacokinetic parameters. Once LC-atmospheric pressure ionization (API) MS-MS analysis was implemented in these same studies, they could be completed in less than one week. The advantages of using LC-API-MS-MS to aid in the drug candidate selection process is demonstrated for one compound (SCH 44342) in this series of FPT inhibitors.

Administration, Oral↗

PubMed1997

cGMP-elevating agents suppress proliferation of vascular smooth muscle cells by inhibiting the activation of epidermal growth factor signaling pathway.

BACKGROUND: Abnormal proliferation of vascular smooth muscle cells (VSMC) is a key event in the pathogenesis of atherosclerosis and many vascular diseases. It is known that nitric oxide released from the endothelium participates in the regulation of VSMC proliferation via a cyclic 3',5'-guanosine monophosphate (cGMP)-mediated mechanism. In a series of experiments, sodium nitroprusside (SNP) and A02131-1 were evaluated for their antiproliferative effect and the mechanism of their cGMP-elevating action. METHODS AND RESULTS: The effect of SNP and A02131-1 on epidermal growth factor (EGF)-stimulated proliferation of rat aortic smooth muscle cells (VSMC) was examined. Cell proliferation was measured in terms of [3H]thymidine incorporation, flow cytometry, and the cell number. Further, their effect on the EGF-activated signal transduction pathway was assessed by measuring mitogen-activated protein kinases (MAPK), MAPK kinase (MEK). Raf-1 activity, and the formation of active form of Ras. SNP and A02131-1 inhibited EGF-induced DNA synthesis and subsequent proliferation of VSMC. These two increased cGMP but only a little cAMP in VSMC. A similar antiproliferative effect was observed with 8-bromo-cGMP. The antiproliferative effect of the two was reversed by KT5823 but not by dideoxyadenosine nor Rp-cAMPS. SNP and A02131-1 blocked the EGF-inducible cell cycle progression at the G1/S phase. Further experiments indicated that the two cGMP-elevating agents primarily blocked the activation of Raf-1 by EGF-activated Ras. CONCLUSIONS: These results demonstrate that cGMP-elevating agents inhibit [3H]thymidine incorporation and thus the growth of VSMC, and this inhibition appears to attenuate EGF-activated signal transduction pathway by preventing Ras-dependent activation of Raf-1.

Amino Acid Sequence↗

PubMed1997

Comparisons of geniposidic acid and geniposide on antitumor and radioprotection after sublethal irradiation.

The antitumor effects of two iridoid compounds, geniposidic acid (GA) and geniposide (GP), were investigated in mice along with their possible effects on radioprotection after sublethal X-irradiation. Decreases in the growth of the implanted tumor by ascitic cells were a result of intraperitoneal administration of GA and GP at high concentrated levels. This result was achieved by exerting the levels of dosage in a dose-dependent manner. Except on the 12th day after treatment by the dosage of 500 mg/kg, reduced radiation effects of mice treated with the drugs in the 30 min preirradiated period by GA and GP on peripheral leukocytes were not observed significantly by the sublethal whole-body X-irradiation. And except on the 7th day after treatment, when these two compounds were administered i.p. to mice 30 min before 4 Gy irradiation, neither GA nor GP enhanced significantly the postirradiation responses of splenic blastogenesis by PHA. In addition, GA might be a more potent tumor growth inhibitor than GP when combined with the X-irradiation, though there was no significant synergetic effect on their combined antitumor activity. The preliminary results of GA and GP on hematological and blastogenic observations in this study suggested that they may very well, partially, play a role in an effective anticancer product with the ability to decrease undesirable radiation damage to the hematologic tissue after high dose irradiation.

Animals↗

PubMed1997

Effects of oleanolic acid and ursolic acid on inhibiting tumor growth and enhancing the recovery of hematopoietic system postirradiation in mice.

Two triterpene acids, oleanolic acid (OA) and ursolic acid (UA) were examined for their ability to inhibit the tumor growth and modify hematopoiesis after irradiation in three experimental systems: (a) in vivo anti-tumor activity of implanted tumor by ascitic cells was found to be augmented by addition of OA and UA at a high concentration and inhibited in a dose-dependent manner; (b) in the sublethal whole-body irradiated mice treated with the drugs in the 30 min preirradiation period, enhanced effects of OA and UA on peripheral leukocytes were observed by a different significance, and (c) when these chemicals were administered i.p. to mice 30 min before 4 Gy irradiation, both OA and UA enhanced the postirradiation responses of splenic blastogenesis by PHA. UA was a more potent tumorigenic inhibitor than OA. Combining with the gamma-irradiation, however, there was no significant synergetic effect on their anti-tumor activity. The beneficial effects of OA and UA on hematopoiesis and immunocompetence under this study, suggested they might partially play a role in anti-cancer and, furthermore, with the ability to decrease undesirable radiation damage to the hematopoietic tissue after radiotherapy.

Animals↗

PubMed1997

Microsample determination of lovastatin and its hydroxy acid metabolite in mouse and rat plasma by liquid chromatography/ionspray tandem mass spectrometry.

A sensitive and specific method was developed and validated to quantitate lovastatin and its hydroxy acid in mouse and rat plasma. This method employs a solid-phase extraction procedure to isolate lovastatin and its hydroxy acid metabolite from the biological matrices (0.1 ml of mouse or rat plasma). The reconstituted extracts were analyzed by liquid chromatography/ionspray tandem mass spectrometry (LC/MS/MS). Simvastatin and simvastatin hydroxy acid were used as internal standards for lovastatin and lovastatin hydroxy acid, respectively. The assay has a lower limit of quantitation (LLQ) of 0.50 ng ml-1 in mouse and rat plasma for both lovastatin and its hydroxy acid based on 0.1 ml aliquots of plasma. The intra- and inter-assay precision (RSD), calculated from quality control (QC) samples, was < 7% for lovastatin and < 6% for lovastatin hydroxy acid in both matrices. The inter-assay accuracy as determined from QC samples was less than 6% for lovastatin and less than 8% for lovastatin hydroxy acid in both matrices. The overall recovery of lovastatin was 54% in mouse plasma and 55% in rat plasma, and the overall recovery of lovastatin hydroxy acid was 100% in mouse plasma and 67% in rat plasma.

Animals↗

PubMed1997

Prenatal diagnosis of partial trisomy 12 and partial trisomy 21 due to a 3:1 segregation of maternal reciprocal translocation t(12;21) (p13.3;q21).

We describe the prenatal diagnosis and fetal phenotype of partial trisomy 12 (p13.3-pter) and partial trisomy 21 (pter-q21) due to a 3:1 segregation with tertiary aneuploidy transmitted from a maternal reciprocal translocation 12;21. Genetic amniocentesis of a 39-year-old gravida 2, para 1 woman at 19 weeks' gestation due to advanced maternal age revealed an unusual karyotype of 47,XY,+der(21)t(12;21)(p13.3;q21)mat. The pregnancy was terminated at 24 gestational weeks. The proband postnatally displayed by dysmorphic features of a round flat face with prominent cheeks and high forehead, upward slanting palpebral fissures, epicanthic folds, hypertelorism, a short nose, a broad and depressed nasal bridge, anteverted nares, a deformed philtrum, an open mouth, thin upper vermilion and broad everted lower lip, low-set ears with prominent anthelix and deep concha, broad hands with simian creases, a short neck, and cryptorchidism. The association of the involved chromosomal segments with the phenotype of Down's syndrome and trisomy 12p syndrome is discussed.

Adult↗

PubMed1997

Single-dose pharmacokinetics of isepamicin in young and geriatric volunteers.

Isepamicin is a new aminoglycoside antibiotic with activity against both gram-negative and gram-positive bacteria. The pharmacokinetics of isepamicin were evaluated after a 0.5-hour intravenous infusion of alpha 15-mg/kg dose to groups of young adults and geriatric volunteers. Isepamicin was safe and well tolerated. No adverse events related to the infusion were reported. As age increased, there were increases in the elimination phase half-life (t1/2 beta) and the area under the plasma concentration-time curve extrapolated to infinity (AUC0-infinity), and decreases in systemic (Cl) and renal clearance (Clr). The changes seen in Cl with age were a result of changes in renal function estimated by creatinine clearance (Clcr). There were no apparent correlations between age and maximum plasma concentration (Cmax), half-life of the tau-phase (t1/2 tau), volume of distribution at steady-state (Vdss), or the amount of isepamicin excreted in urine within 24 hours after dose administration (Ae24 hrs). When comparing the elderly (61-80 years old) with the younger (21-60 years) volunteers, the (AUC0-infinity), and t1/2 beta values were higher in the elderly and the Cl and Clr values were lower, but Cmax, t1/2 tau and Vdss were similar in the two age groups. The contribution of the tau-phase to the overall AUC was minimal and similar for the two age groups. Also, there were no gender effects on the pharmacokinetics of isepamicin in both the young and elderly volunteers. These results demonstrate that changes in the pharmacokinetics of isepamicin in the elderly are attributable to changes in renal function, whereas age, per se, is not a significant factor.

Adult↗

PubMed1997

Comparison technetium of Tc-99m disofenin cholescintigraphy with ultrasonography in the differentiation of biliary atresia from other forms of neonatal jaundice.

Technetium Tc-99m disofenin cholescintigraphy (CS) and ultrasonography (US) are two major clinical methods used in differentiating biliary atresia (BA) from neonatal jaundice. To compare the diagnostic utility of these two modalities, 66 patients with neonatal cholestasis (15 BA, 3 choledochal cyst (CC), 32 neonatal hepatitis, 13 prolonged jaundice, 2 total parenteral nutrition, and 1 sepsis) underwent Tc-99m disofenin CS and US. The diagnostic sensitivity, specificity, and accuracy of CS in differentiating BA from other forms of neonatal jaundice was 100%, 87.5%, and 90.5%, respectively, and for US 86.7%, 77.1%, and 79.4%, respectively. Tc-99m disofenin CS after premedication with phenobarbital and cholestyramine is a convenient and reliable method of differentiating BA from neonatal hepatitis, with a diagnostic accuracy superior to that of US. However, US is the initial imaging procedure of choice in patients presenting with jaundice to rule out anatomic anomalies such as CC.

Biliary Atresia↗

PubMed1997

Higher-order organization of subrepeats and the evolution of cervid satellite I DNA.

Based on sequence analyses of 17 complete centromeric DNA monomers from ten different deer species, a model is proposed for the genesis, evolution, and genomic organization of cervid satellite I DNA. All cervid satellite I DNA arose from the initial amplification of a 31-bp DNA sequence. These 31-bp subrepeats were organized in a hierarchical fashion as 0.8-kb monomers in plesiometacarpalia deer and 1-kb monomers in telemetacarpalia deer. The higher-order repeat nature of cervid centromeric satellite DNA monomers accounts for their high intragenomic and intraspecific sequence conservation. Such high intraspecific sequence conservation validates the use of a single cervid satellite I DNA monomer from each deer species for interspecific sequence comparisons to elucidate phylogenetic relationships. Also, a specific 0.18-kb tandem duplication was observed in all 1-kb monomers, implying that 1-kb cervid satellite I DNA monomers arose from an unequal crossover event between two similar 0.8-kb ancestral DNA sequences.

Animals↗

PubMed1997

Chromosomal evolution of the Chinese muntjac (Muntiacus reevesi).

The aim of this study was to test the validity of the hypothesis that the 2n=46 karyotype of the Chinese muntjac (Muntiacus reevesi) could have evolved through 12 tandem fusions from a 2n=70 hypothetical ancestral karyotype, which is still retained in Chinese water deer (Hydropotes inermis) and brown-brocket deer (Mazama gouazoubira). Combining fluorescence-activated chromosomal sorting and degenerate oligonucleotide-primed polymerase chain reaction, we generated chromosome-specific DNA paint probes for 13 M. gouazoubira chromosomes and most of the M. reevesi chromosomes with the exception of 18, 19 and X. These paint probes were used for fluorescence in situ hybridisation to chromosomal preparations of M. reevesi, H. inermis and M. gouazoubira. Chromosome-specific paint probes from M. reevesi chromosomes 1-5 and 11 each delineated more than one homologous pair (18 pairs in total) on the metaphases of H. inermis and M. gouazoubira. All the other probes from M. reevesi and probes from M. gouazoubira each hybridised to one pair of homologous chromosomes or regions. The C5 probe, derived from centromeric satellite sequences of M. reevesi, hybridised to the centromeric regions of all chromosomes of these three species. Most interestingly, several non-random interstitial signals, which are apparently localised to the putative fusion points, were found on chromosomes 1-5 and 11 of M. reevesi. Both the reciprocal painting patterns and localisation of the C5 probe demonstrate that M. reevesi chromosomes 1-5 and 11 could have evolved from 18 different ancestral chromosomes through 12 tandem fusions, thus providing direct molecular cytogenetic support for the tandem fusion hypothesis of karyotype evolution in M. reevesi.

Animals↗

PubMed1997

Serum levels of intercellular adhesion molecule-1 and E-selectin in patients with acute ischaemic stroke.

To investigate the role of circulating intercellular adhesion molecule-1 (ICAM-1) and E-selectin in ischaemic stroke, serum levels of ICAM-1 and E-selectin were measured by ELISA in 51 patients with acute ischaemic stroke within 24 h, and in 25 age-matched healthy controls and 10 young healthy volunteers. Carotid Doppler ultrasonography showed a significant stenosis (> 50%) of the carotid or vertebrobasilar artery in 11 of 51 stroke patients. Serum levels of ICAM-1 [mean (SE)] were higher (P < 0.01) in patients with ischaemic stroke [381 (30) ng/ ml] than in age-matched controls [271 (27) ng/ml] and young controls [246 (6) ng/ml]. There was no significant difference in serum E-selectin levels [mean (SE)] among stroke patients, age-matched and young controls [47 (6), 39 (3), and 41 (3) ng/ ml, respectively; P = NS]. The leucocyte count [mean (SD)] was higher (P < 0.01) in patients with ischaemic stroke [8310 (2800)] than in age-matched controls [6040 (930)]. Serum levels of ICAM-1 and E-selectin did not significantly differ between patients with or without abnormal carotid or vertebrobasilar artery disease. In conclusion, serum ICAM-1 level and leucocyte count were elevated in acute ischaemic stroke within 24 h, while the E-selectin level did not change significantly. This finding suggests that adhesion molecules may play an important role in the post-rolling process of leucocyte-endothelial cell interaction in acute ischaemic stroke.

Aged↗

PubMed1997

Human centromeric DNAs.

Human centromeres have been extensively studied over the past two decades. Consequently, more is known of centromere structure and organization in humans than in any other higher eukaryote species. Recent advances in the construction of a human (or mammalian) artificial chromosome have fostered increased interest in determining the structure and function of fully functional human centromeres. Here, we present an overview of currently identified human centromeric repetitive DNA families: their discoveries, molecular characterization, and organization with respect to other centromeric repetitive DNA families. A brief examination of some functional based studies is also included.

Animals↗