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Biomedical subjects

C M Chen

Publications and source records attributed to C M Chen.

At least 145 records · Page 8Linked to original sources

Isolation and expression of a porcine lactoferrin gene.

OBJECTIVE: To elucidate the spatial and temporal expression of a porcine lactoferrin (LTF) gene. ANIMALS: 4 female and 4 male Large White pigs. PROCEDURES: We examined LTF expression in various organs excised from the pigs, using northern blot hybridization with a porcine LTF cDNA probe. Antibodies against porcine LTF were raised in rabbits and were used along with immunohistochemical staining to localize the LTF protein. RESULTS: High amounts of porcine LTF mRNA were detected in the secreting mammary gland and epididymis. This distribution is consistent with that of porcine LTF examined by immunohistochemistry. In female pigs, porcine LTF mRNA concentration increased remarkably in the ductal cells of the lactating mammary gland then significantly decreased at day 21 after parturition. Furthermore, specific staining for LTF was observed in the epithelial cells of the gastrointestinal tract of female pigs, but not in the uterus, ovaries, spleen, kidneys, pancreas, muscles, heart, brain, lungs, or liver of postpartum female pigs, or in the testes of male pigs. CONCLUSIONS: Gene expression of porcine LTF is closely related to lactation in the mammary gland. Distribution of LTF in the epididymis suggests that LTF may have a regulatory role in development of the reproductive tract of male pigs.

Animals↗

Determination of Z-butylidenephthalide in plasma by high-performance liquid chromatography.

An HPLC assay is described for the determination of Z-butylidenephthalide (Z-Bdph) in plasma. Plasma samples were cleaned up by extraction with 2% chloroform in n-hexane. Z-Bdph was separated on a normal-phase silica column with a mobile phase of chloroform-n-hexane (1:1). The limit of quantitation with UV detection at 254 nm for Z-Bdph in plasma was 0.01 microgram/ml. The recovery of Z-Bdph by organic solvent extraction of plasma was 99.5%. The intra-day and inter-day coefficients of variation and relative errors for Z-Bdph determination in plasma were both less than 10%. The present method was applied to pharmacokinetic studies of Z-Bdph in plasma after intravenous administration to rabbits.

Animals↗

I-mf, a novel myogenic repressor, interacts with members of the MyoD family.

During embryogenesis, cells from the ventral and dorsal parts of the somites give rise to sclerotome and dermomyotome, respectively. Dermomyotome contains skeletal muscle precursors that are determined by the MyoD family of myogenic factors. We have isolated a novel myogenic repressor, I-mf (Inhibitor of MyoD family), which is highly expressed in the sclerotome. In contrast, MyoD family members are concentrated in the dermomyotome. We demonstrate that I-mf inhibits the transactivation activity of the MyoD family and represses myogenesis. I-mf associates with MyoD family members and retains them in the cytoplasm by masking their nuclear localization signals. I-mf can also interfere with the DNA binding activity of MyoD family members. We postulate that I-mf plays an important role in the patterning of the somite early in development.

3T3 Cells↗

Requirement for alpha-CaMKII in experience-dependent plasticity of the barrel cortex.

The mammalian sensory neocortex exhibits experience-dependent plasticity such that neurons modify their response properties according to changes in sensory experience. The synaptic plasticity mechanism of long-term potentiation requiring calcium-calmodulin-dependent kinase type II (CaMKII) could underlie experience-dependent plasticity. Plasticity in adult mice can be induced by changes in the patterns of tactile input to the barrel cortex. This response is strongly depressed in adult mice that lack the gene encoding alpha-CaMKII, although adolescent animals are unaffected. Thus, alpha-CaMKII is necessary either for the induction or for the expression of plasticity in adult mice.

Animals↗

Molecular analysis of cellular loci disrupted by papillomavirus 16 integration in cervical cancer: frequent viral integration in topologically destabilized and transcriptionally active chromosomal regions.

To discern the structural features of cellular loci that are disrupted by type 16 human papillomavirus (HPV-16) integration in cervical cancer, a polymerase chain reaction (PCR)-based strategy was employed for direct amplification and sequence analysis of four such cellular loci in cancer biopsy samples. One of the HPV-16-disrupted loci was found to be the microtubule-associated protein (MAP-2) gene and the other three loci were uncharacterized and were designated PID-1 to -3 (for papillomavirus integration-disrupted). The junctional sequences of the viral integration sites in the four loci analyzed are bracketed by long tracts of homogeneous purine or pyrimidine or alternating purine-pyrimidine which are known to destabilize the B-form conformation of the DNA structure. Using a panel of human/hamster hybrid cell DNAs and PCR analysis, the four loci were assigned to chromosomes 2 (MAP-2), 9 (PID-1), 1 (PID-2) and 8 (PID-3), respectively. These chromosomes carry numerous other previously determined viral integration and chromosomal fragile sites and the myc oncogenes. The PID-1 locus was further found in Southern analysis to be rearranged and amplified in another cervical cancer biopsy and a cervical carcinoma cell line (CaSki). On Northern analysis, the PID-1 and -3 probes detected a 3.0- and a 3.6-kb transcript, respectively, in normal cervical cells and in cervical cancer cell lines. The findings suggest that HPV-16 genome integrates frequently into topologically destabilized and transcriptionally active chromosomal sites. It remains to be elucidated whether the MAP-2 and the PID loci contribute to the pathogenesis of cervical cancer.

Base Sequence↗

Pharmacokinetics of higenamine in rabbits.

The pharmacokinetics of higenamine were investigated in rabbits by IV bolus, PO route, and IV infusion. Plasma higenamine concentration declined rapidly in a biexponential pattern, with a terminal half-life of 22 min. The AUC increased proportionally with increasing dose, whereas the percentage of unchanged higenamine excreted from urine remained constant when dose was increased. The means of total body clearance, mean residence time, volume of distribution at steady state, and fraction of urinary excretion were 127.7 mL min-1 kg-1, 9.28 min, 1.44 kg-1, and 5.48%, respectively. The mean percentage of protein binding of higenamine in plasma was 54.8% at steady state after IV infusion. The results from post-infusion also confirmed that higenamine followed a two-compartment open model in animals. After oral administration, higenamine was rapidly absorbed to reach peak concentration within 10 min. Interestingly, the plasma concentration-time profiles revealed two distinguishable groups with different Cmax, extent of absorption, and urinary excretion. The average absolute bioavailabilities of higenamine calculated by AUCs and accumulated urinary excretion were 21.86 and 2.84% versus 20.19 and 5.50% for the two groups, respectively. Upon hydrolysis of urine samples with beta-glucuronidase, urinary concentrations of higenamine were greatly enhanced in both groups.

Administration, Oral↗

Strength in Parkinson's disease: relationship to rate of force generation and clinical status.

Maximum elbow flexor and extensor muscle strength was measured in 9 patients with Parkinson's disease on and off antiparkinsonian medication. In addition, the rate of force generation, the rate of actively returning force to resting levels, and passive release of force "relaxation" were measured in submaximal contractions. The measures of strength and contraction time were correlated with changes in clinical status as measured by the Unified Parkinson's Disease Rating Scale. When patients were off medication, their reduction in strength was significantly greater in extension than flexion. The reduction in flexion strength did not reach statistical significance. The extensor weakness was primarily due to decreased tonic activation of the extensor muscles and not to muscle coactivation. Muscle relaxation time was much more prolonged than was force generation time or active force return time. The increase in relaxation time and the decrease in extensor strength both correlated with changes in clinical status. Finally, changes in extensor torque correlated with the time to actively return force, suggesting that reduced strength is related to a reduced ability to generate rapid contractions in some patients with Parkinson's disease. These results suggest that there is an asymmetric distribution of muscle weakness in Parkinson's disease and that selected measures of muscle strength and muscle relaxation correlate with changes in clinical status.

Aged↗

Transcriptional regulation of hydroxypyruvate reductase gene expression by cytokinin in etiolated pumpkin cotyledons.

To understand the mechanisms by which the expression of a specific gene is modulated by cytokinin, the regulation of hydroxypyruvate reductase (HPR) transcript levels by N6-benzyladenine (BA) in etiolated pumpkin (Cucurbita pepo L. cv. Halloween) cotyledons was investigated. A pumpkin HPR cDNA was generated by reverse transcriptase-polymerase chain reaction and its nucleotide sequence was determined. An antisense HPR RNA was prepared for RNase protection analysis of HPR-mRNA expression patterns in the cotyledons of dark-grown pumpkin seedlings. Treatment of the cotyledons with BA was shown to modulate HPR mRNA levels in a dose- and time-dependent manner. Similarly, nuclear run-on studies showed that the rate of transcription was also enhanced by BA treatment of the cotyledons. These results suggest that the enhancement of HPR mRNA by cytokinin is, at least in part, at the level of transcription.

Adenine↗

Fractures of posterior wall of acetabulum.

Fractures of the posterior wall of the acetabulum form a special group in acetabular fractures. This study aims to evaluate the results in the management of such fractures. Thirty-two patients with fractures of posterior wall of acetabulum were reviewed retrospectively. The follow-up period was 7 (range 3-10) years. Twenty-four were associated with initial posterior dislocations. Twenty-seven were managed with open reduction and internal fixation, while the remainder were managed conservatively. Reductions were rated as congruent in 30 cases and as noncongruent in 2. The functional results were excellent in 16 cases, good in 10, fair in 2, and poor in 4. Two early complications were met, namely 1 iatrogenic sciatic nerve injury and 1 superficial wound infection. Sixteen late complications were noted, including 10 heterotopic ossifications, 3 avascular necroses of femoral head, and 3 symptomatic arthritides. The incidence of late complications was high, but the functional results were generally satisfactory. Congruent reduction was the key in obtaining satisfactory results in the management of these fractures.

Acetabulum↗

Percutaneous pinning in undisplaced subcapital femoral neck fractures.

Three hundred and five undisplaced subcapital femoral neck fractures managed by pinning in situ with Knowles' pins were evaluated to elucidate the role and effect of such treatment. The protocol of management and follow up, and evaluation, both radiographically and functionally, were set up prospectively. The duration from injury to management was 3.5 (1-14) days, the operation time was 22 (9-48) min and most of the patients were discharged without hospitalization. The follow-up period was 75 (28-136) months. The final results showed 282 (92.5 per cent) fractures united without complications (mean union time: 20 weeks), 14 (4.6 per cent) limbs with non-union, and 9 (2.9 per cent) had implant problems. Twenty-two (7.2 per cent) developed avascular necrosis after union. Percutaneous pinning of undisplaced subcapital femoral neck fractures as day cases is a simple, safe, effective and economic method.

Adult↗

Polychaetoid is required to restrict segregation of sensory organ precursors from proneural clusters in Drosophila.

Reduction of wild-type activity of the polychaetoid (pyd) gene results in formation of extra mechanosensory bristles on the head and notum of adult Drosophila. Loss of pyd function results in decreased ability to restrict sensory organ precursor (SOP) formation to a single cell per proneural cluster. Although the initial proneural cluster pattern of achaete expression is not altered in pyd mutants, extra cells within proneural clusters express the high levels of achaete characteristic of SOPs. This observation suggests that pyd+ functions as a negative regulator of achaete-scute complex expression within the proneural cluster. Synergistic interactions between pyd and Notch, Delta and extramacrochaetae mutations support this model. We also demonstrate that pyd is required for normal eye development.

Alleles↗

Mechanisms underlying experience-dependent potentiation and depression of vibrissae responses in barrel cortex.

Plasticity was studied in the barrel cortex of rats and mice. Vibrissae deprivation in adult and adolescent animals caused changes in the response properties of cortical neurons to stimulation of spared and deprived vibrissae. Plasticity involved both potentiation of spared vibrissae responses and depression of deprived vibrissae responses in layer II/III of the cortex. Vibrissae response potentiation was found to require alpha CaMKII in adult cortex. Vibrissae response depression was not found to occur in adult cortex but was found in adolescent animals for the principal vibrissa. Preliminary results suggested that vibrissae response depression exhibits both hetero- and homosynaptic components.

Animals↗

Prevalence and type of precore hepatitis B virus mutants in hepatitis D virus superinfection and its clinical implications.

To study the prevalence and type of the hepatitis B e antigen (HBeAg)-negative mutant in hepatitis D virus (HDV) superinfection, the precore region of hepatitis B virus (HBV) was analyzed by cycle sequencing. Of the 58 samples sequenced, 24 were wild type and 34 carried mutants. The precore stop mutation (TAG) at the 28th codon was found in 32 cases, other mutations were found in 7, and double mutations were found in 5. The absence of HBeAg showed a substantial agreement with the presence of mutants (kappa value, 0.74). Of the acute hepatitis patients, HDV replication and clinical manifestations were not significantly different between those with mutant and wild type virus, except that those with mutant virus were older (mean age, 48 vs. 28 years; P < .002). The absence of HBeAg in these patients is mainly due to HDV superinfection in older HBV carriers who already had precore mutant.

Acute Disease↗

Multicenter trial of modified Gamma nail in East Asia.

The mismatch of the standard Gamma nail in the Chinese femora led to the modification of its femoral shaft component based on the anthropometric study of 28 pairs of Chinese femora. A multicenter clinical trial was done in 6 countries and regions in East Asia. Three hundred forty-nine fractures were treated and studied. More than 60% of the fractures were unstable by Evans classification. The average age of the patients was 73.6 years. The male to female ratio was 2:3. The mean followup period was 11.7 months. The result of the trial showed that the intraoperative complication rate was 7.7%, and complications primarily were related to faulty operative technique. There were 7.2% postoperative complications related to the fractures that again decreased toward the later stage of the trial. Functionally, there was progressive improvement of the hip score within the followup period. The results show that the modified Gamma nail gave better results in the treatment of geriatric trochanteric fractures by minimizing reaming, thereby reducing complications related to the implants.

Activities of Daily Living↗

Unstable closed tibial shaft fractures: a prospective evaluation of surgical treatment.

OBJECTIVE: To define the roles of the rigid interlocking nail and the semirigid Ender nail in the treatment of closed unstable tibia] shaft fractures. DESIGN: Randomized, clinical, prospectively study with detailed comparison of parameters. MATERIALS AND METHODS: Data on 116 unstable closed tibial shaft fractures were collected. Randomly, 60 tibiae were fixed with interlocking nails and 56 tibiae were fixed with Ender nails. The follow-up period was 24 (16-32) months. MEASUREMENTS AND MAIN RESULTS: In the interlocking nail group, the average blood loss was 189 cc, operation time was 51 minutes, length of hospital stay was 7 days, and union time was 14.2 weeks. In the Ender nail group, the average blood loss was 95 cc, operation time was 30 minutes, length of hospital stay was 5.0 days, and union time was 16.9 weeks. Student's t test was used for statistical significance. CONCLUSIONS: For more comminuted unstable tibial shaft fractures, an interlocking nail is undoubtedly a better choice, but an Ender nail still is effective in some aspects of treatment in the less comminuted unstable tibial shaft fractures.

Adolescent↗

(+/-)-Govadine and (+/-)-THP, two tetrahydroprotoberberine alkaloids, as selective alpha 1-adrenoceptor antagonists in vascular smooth muscle cells.

(+/-)-Govadine and (+/-)-THP ((+/-)-2,3,10,11-tetrahydroxytetrahydroprotoberberine HBr) have been shown to inhibit noradrenaline-induced contraction of rat thoracic aortae. The pharmacological activity of the compounds was determined in thoracic aortae and cardiac tissue isolated from the rat and in trachea isolated from the guinea-pig to determine the selectivity of the compounds towards different types of receptor. (+/-)-Govadine and (+/-)-THP were found to be alpha 1-adrenoceptor blocking agents in rat thoracic aorta as revealed by their competitive antagonism of vasoconstriction induced by noradrenaline (pA2 = 6.57 +/- 0.07 and 5.93 +/- 0.06, respectively) or phenylephrine (pA2 = 6.74 +/- 0.08 and 6.06 +/- 0.10, respectively). Removal of endothelium did not affect the antagonistic potencies of (+/-)-govadine (pA2 = 6.83 +/- 0.09) and (+/-)-THP (pA2 = 6.25 +/- 0.06) on phenylephrine-induced vasoconstriction. They were more potent than yohimbine (pA2 = 6.05 +/- 0.05), but less so than phentolamine (pA2 = 7.54 +/- 0.11) and prazosin (pA2 = 9.27 +/- 0.12). (+/-)-Govadine and (+/-)-THP, furthermore, inhibited [3H]inositol monophosphate formation caused by noradrenaline (3 microM) in rat thoracic aorta. (+/-)-Govadine and (+/-)-THP were also alpha 2-adrenoceptor blocking agents with pA2 values 5.50 +/- 0.13 and 5.41 +/- 0.11, respectively. A high concentration of (+/-)-govadine (30 microM) or (+/-)-THP (30 microM) did not, however, affect the contraction induced by the thromboxane receptor agonist U46619, prostaglandin F2 alpha (PGF2 alpha), 5-hydroxytryptamine (5-HT), angiotensin II, endothelin or high K+ in rat aorta denuded of endothelium. Neither the cyclic AMP nor cyclic GMP content of rat thoracic aorta was, furthermore, changed by (+/-)-govadine or (+/-)-THP. Contraction of guinea-pig trachea caused by carbachol, histamine, leukotriene C4 or neurokinin A was not affected by (+/-)-govadine or (+/-)-THP. (+/-)-Govadine or (+/-)-THP also did not block beta 1- or beta 2-adrenoceptor-mediated responses induced by isoprenaline in rat right atria and guinea-pig trachea. It is concluded that (+/-)-govadine and (+/-)-THP are selective alpha 1-adrenoceptor antagonists in vascular smooth muscle.

Adrenergic alpha-1 Receptor Agonists↗

Pharmacological characteristics of BDTI, a new isoquinoline-derived beta 2-adrenoceptor agonist, in canine trachea and rat heart.

The tracheal relaxing effects and beta 2-selectivity of BDTI (1-benzyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline HBr) were investigated in canine trachea and rat heart by radioligand binding assay and pharmacological experiments in comparison with those of other beta-adrenoceptor agonists, salbutamol and isoprenaline. The potency of relaxing effect on carbachol-induced contraction in isolated canine trachea was in the order of isoprenaline (pD2 = 6.70 +/- 0.08) > BDTI (6.11 +/- 0.06) approximately salbutamol (6.14 +/- 0.08). ICI-118,551 (a selective beta 2-antagonist) and atenolol (a selective beta 1-antagonist) inhibited the relaxant action of BDTI with pKB values of 8.4 and 5.3, respectively, corresponding to high affinity for ICI-118,551 and low affinity for atenolol in antagonizing this response. The Kd values of radioligand ([3H]-CGP12177) were 453.3 +/- 30.8 and 563.4 +/- 96.7 pmol/l in cultured canine tracheal smooth muscle cells (TSMCs) and rat cardiomyocytes, respectively, and the Bmax values were 64.6 +/- 10.7 and 245.7 +/- 44.5 fmol/mg protein, respectively. BDTI, salbutamol and isoprenaline inhibited the binding of [3H]-CGP12177 in a concentration-dependent manner in cultured canine TSMCs (Ki 0.73 +/- 0.15, 0.75 +/- 0.21 and 0.24 +/- 0.05 mumol/l, respectively) and rat cardiomyocytes (Ki 2.76 +/- 0.36, 2.31 +/- 0.26 and 0.22 +/- 0.03 mumol/l, respectively). These results demonstrated that BDTI possessed moderate selectivity (3.8-fold) to beta 2-adrenoceptors as judged from the Ki (heart)/Ki (trachea) value (salbutamol 3.1-fold, isoprenaline 0.92-fold). BDTI and salbutamol also stimulated cAMP formation in a concentration-dependent manner in cultured canine TSMCs (EC50 0.5 +/- 0.2 and 0.4 +/- 0.1 mumol/l, respectively) and rat cardiomyocytes (EC50 6.2 +/- 0.5 and 5.7 +/- 0.6 mumol/l, respectively). The selectivity of BDTI and salbutamol for beta 2-adrenoceptors on the cAMP response were 12.4 and 14.3 times, respectively. It is concluded that BDTI is a beta 2-selective adrenoceptor agonist.

Adrenergic beta-2 Receptor Agonists↗