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Biomedical subjects

F M Chen

Publications and source records attributed to F M Chen.

At least 19 recordsLinked to original sources
PubMed2006

Activation of extracellular signal-regulated kinase (ERK) in G2 phase delays mitotic entry through p21CIP1.

Extracellular signal-regulated kinase activity is essential for mediating cell cycle progression from G(1) phase to S phase (DNA synthesis). In contrast, the role of extracellular signal-regulated kinase during G(2) phase and mitosis (M phase) is largely undefined. Previous studies have suggested that inhibition of basal extracellular signal-regulated kinase activity delays G(2)- and M-phase progression. In the current investigation, we have examined the consequence of activating the extracellular signal-regulated kinase pathway during G(2) phase on subsequent progression through mitosis. Using synchronized HeLa cells, we show that activation of the extracellular signal-regulated kinase pathway with phorbol 12-myristate 13-acetate or epidermal growth factor during G(2) phase causes a rapid cell cycle arrest in G(2) as measured by flow cytometry, mitotic indices and cyclin B1 expression. This G(2)-phase arrest was reversed by pre-treatment with bisindolylmaleimide or U0126, which are selective inhibitors of protein kinase C proteins or the extracellular signal-regulated kinase activators, MEK1/2, respectively. The extracellular signal-regulated kinase-mediated delay in M-phase entry appeared to involve de novo synthesis of the cyclin-dependent kinase inhibitor, p21(CIP1), during G(2) through a p53-independent mechanism. To establish a function for the increased expression of p21(CIP1) and delayed cell cycle progression, we show that extracellular signal-regulated kinase activation in G(2)-phase cells results in an increased number of cells containing chromosome aberrations characteristic of genomic instability. The presence of chromosome aberrations following extracellular signal-regulated kinase activation during G(2)-phase was further augmented in cells lacking p21(CIP1). These findings suggest that p21(CIP1) mediated inhibition of cell cycle progression during G(2)/M phase protects against inappropriate activation of signalling pathways, which may cause excessive chromosome damage and be detrimental to cell survival.

Butadienes↗
PubMed2006

Molecular detection of disseminated tumor cells in the peripheral blood of patients with gastric cancer: evaluation of their prognostic significance.

Early detection of disseminated tumor cells in the peripheral blood of patients with early stage gastric cancer could help to improve the outcome after tumor resection. The aim of this study is to evaluate the prognostic significance of tumor-related mRNA for the detection of circulating tumor cells in gastric cancer patients by a reverse-transcriptase polymerase chain reaction (RT-PCR) method. We simultaneously analyzed human telomerase reverse transcriptase (hTERT), cytokeratin-19 (CK-19), cytokeratin-20 (CK-20) and carcinoembryonic antigen (CEA) mRNA (messenger RNA) expression in the peripheral blood of 42 gastric cancer patients and 30 healthy individuals. Additionally, analyses were carried out for the correlation of these four molecular markers with patients' clinicopathologic features, as well as the occurrence of postoperative recurrence/metastasis. Among 42 gastric cancer patients, the prevalence of mRNA for hTERT, CK-19, CK-20, and CEA was 61.9% (26/42), 69% (29/42), 61.9% (26/42), and 78.6% (33/42), respectively. All 30 healthy individuals were negative for hTERT and CEA mRNA, while two were positive for either CK-19 mRNA or CK-20 mRNA. Positive CEA mRNA was significantly correlated with tumor size p=0.008), vessel invasion (p=0.001), depth of tumor invasion (p=0.007), lymph node metastasis (p< 0.001), and TNM stage (p<0.001). In addition, the multivariate logistic regression demonstrated that CEA mRNA expression was an independent and significant predictor for postoperative recurrence/metastasis (p=0.032). Our findings suggest that CEA mRNA may be a more reliable marker than hTERT, CK-19 and CK-20 for the detection of circulating cancer cells in gastric cancer patients' peripheral blood. Patients with positive CEA mRNA expression in peripheral blood have a significantly higher risk of postoperative recurrence/metastasis.

Adult↗
PubMed2001

Actinomycin D binds strongly to d(TGTCATTG), a single-stranded DNA devoid of GpC sites.

Despite the absence of the GpC sequence and complete self-complementarity, d(CGTCGTCG) has recently been shown to bind strongly to actinomycin D (ACTD) with a binding density of about one drug molecule per strand. To further elucidate the nature of such a binding, studies are herein made with single-base G --> A and C --> T replacements in d(CGTCGTCG) to identify the DNA bases that play important roles in the strong ACTD binding of this oligomer. On the basis of these results, the octamer d(TGTCATTG) has been identified as a potentially strong ACTD binder. Indeed, binding titration confirms such an expectation and reveals an ACTD binding constant of about 1 x 10(7) M(-1) and a binding density of roughly 0.8 drug molecule per DNA strand for this strong binding mode. Similar binding studies with single-base substitutions on d(TGTCATTG) further reveal the relative importance of the C and G bases on its ACTD binding, with the 3'-terminus G appearing to be the most crucial base. Further base substitutions lead to the conclusion that these C and G bases act in concert rather than individually in the ACTD binding of d(TGTCATTG). Spectral comparisons with the apparently single-stranded GpC-containing d(TGCTTTG) led to the proposal of a speculated monomeric hairpin binding model to account for the experimental observations. This model makes use of the notion that ACTD prefers to have the 3'-sides of both G bases stacking on the opposite faces of its planar phenoxazone chromophore, a principle akin to its classic preference for the GpC sequence in duplex form. The finding that ACTD can bind strongly to single-stranded DNA of special sequence motifs may have important implications.

Adenine↗
PubMed2001

Antibiotic treatment for threatened abortion during the early first trimester in women with previous spontaneous abortion.

BACKGROUND: We retrospectively examined the usefulness of antibiotic therapy for management of first-trimester threatened abortion in women with previous spontaneous abortion. METHODS: From 1993 through 1999, women with first-trimester threatened abortion received antibiotic therapy. Only those with gestational age less than 9 weeks and previous spontaneous abortion were included in this analysis. Women with mild abdominal cramping received amoxicillin plus erythromycin for 1 week; those with severe abdominal pain received amoxicillin plus clindamycin for 1 week. Recurrence was documented on the basis of either lower abdominal pain or vaginal bleeding. RESULTS: Of the 23 women included, 15 (65%) had abnormal vaginal flora (a score above 4, Nugent's criteria). Seven of 16 women who received amoxicillin plus clindamycin and three of seven who received amoxicillin plus erythromycin had complete resolution of lower abdominal pain and vaginal bleeding without recurrence (p=1). The recurrence rate was higher, though not significantly, in women with abnormal bacterial vaginal flora (8/15 vs. 2/8, p=0.379). Twenty-two (96%) of the 23 pregnancies were carried to term, with no identifiable neonatal anomalies. CONCLUSIONS: These results suggest the usefulness of early antibiotic therapy in preventing pregnancy loss in women with threatened abortion early in the first trimester, and warrant further clinical trials.

Abortion, Spontaneous↗
PubMed2001

Role conflicts of physicians and their family members: rules but no rulebook.

OBJECTIVES: To elucidate the difficulties physicians have when a family member becomes ill and to elicit their underlying causes. DESIGN: Using a key informant technique, we solicited chairs of family medicine departments for their experiences with the health care provided to seriously ill family members. We then conducted in-depth, semistructured telephone interviews that were then transcribed, coded, and labeled for themes. SUBJECTS: 8 senior family physicians whose parents had experienced a serious illness within the past 5 years. All of the subjects reflected on experiences stemming from their fathers' illness. RESULTS: These physicians faced competing expectations: at an internal level, those of their ideal role in their family and their ideal professional identity; and at an external level, those originating from other family members and from other physicians. Reconciling these conflicting expectations was made more difficult by what they deemed to be suboptimal circumstances of the modern health care system. CONCLUSIONS: Conflicting rules of appropriate conduct, compounded by the inadequacies of modern health care, make the role of physician-family member especially challenging. The medical profession needs a clearer, more trenchant understanding of this role.

Adult↗
PubMed2001

Dermatology referrals in an academic family medicine clinic.

BACKGROUND: Variations in referral rates among primary care physicians have implications for cost and quality of care, as well as primary care training. Dermatology referral rates of residents and faculty from an academic family medicine clinic are described. METHODS: Using a computerized referral tracking system, all dermatology referrals from January to March 1999 were retrospectively reviewed. Referral rates were calculated for individual providers, rates of uncompleted referrals were calculated, and reasons for referral were examined. RESULTS: Residents and faculty made 102 dermatology referrals during the study period. Although no significant differences occurred in referral rates between residents and faculty, significant variation occurred among individual providers. Junior residents had more uncompleted referrals (83%) than senior residents (29%) and faculty. Common skin conditions accounted for most referrals. CONCLUSIONS: Wide variation exists in dermatology referral rates among family medicine residents and faculty. Moreover, many referral appointments are not kept. Family medicine training curricula should include formal education on the referral process.

Academic Medical Centers↗
PubMed2001

Family physicians' personal experiences of their fathers' health care.

OBJECTIVES: The American health care system is complicated and can be difficult to navigate. The physician who observes the care of a family member has a uniquely informed perspective on this system. We hoped to gain insight into some of the shortcomings of the health care system from the personal experiences of physician family members. STUDY DESIGN: Using a key informant technique, we invited by E-mail any of the chairpersons of US academic departments of family medicine to describe their recent personal experiences with the health care system when their parent was seriously ill. In-depth semi-structured telephone interviews were conducted with each of the study participants. The interviews were transcribed, coded, and labeled for themes. POPULATION: Eight family physicians responded to the E-mail, and each was interviewed. These physicians had been in practice for an average of 19 years, were nationally distributed, and included both men and women. Each discussed their father's experience. RESULTS: All participants spoke of the importance of an advocate for their fathers who would coordinate medical care. These physicians witnessed various obstacles in their fathers's care, such as poor communication and fragmented care. As a result, many of them felt compelled to intervene in their fathers' care. The physicians expressed concern about the care their fathers received, believing that the system does not operate the way it should. CONCLUSIONS: Even patients with a knowledgeable physician family member face challenges in receiving optimal medical care. Patients might receive better care if health care systems reinforced the role of an accountable attending physician, encouraged continuity of care, and emphasized the value of knowing the patient as a person.

Family↗
PubMed2001

Rectal administration of misoprostol for the management of retained placenta--a preliminary report.

BACKGROUND: Retained placenta is one of the serious complications of childbirth, and misoprostol is known to be a potent uterotonic agent. Therefore, we proposed that rectal misoprostol also may facilitate placental separation in women with retained placenta by its ability to increase uterine contractility. METHODS: The placenta was diagnosed as retained if it was not expelled within 40 minutes after vaginal birth. Then, 800 microg of misoprostol was inserted rectally and the patient observed thereafter. RESULTS: A total of 18 parturients who had retention of the placenta were studied; all the placentas were spontaneously expelled within 35 minutes. The side effects involved included nausea 17%, vomiting 11%, diarrhea 22%, shivering 33%, and pelvic cramping pain 44%. All these discomforts resolved within 24 hours. CONCLUSIONS: Our study demonstrated that misoprostol per rectum is a safe and effective technique and may be a useful alternative to manual removal of retained placentas.

Abortifacient Agents, Nonsteroidal↗
PubMed2000

Actinomycin D binds strongly to d(CGACGACG) and d(CGTCGTCG).

Earlier calorimetric studies had indicated that despite the absence of a GpC sequence, the self-complementary octamer d(CGTCGACG) binds strongly to actinomycin D (ACTD) with high cooperativity and a 2:1 drug/duplex ratio. A subsequent optical spectral study with related oligomers led us to suggest that ACTD may likely stack at the G. C basepairs of the duplex termini. New findings are reported herein to indicate that despite the lack of complete self-complementarity, oligomers of d(CGXCGXCG) [X = A or T] motif exhibit unusually strong ACTD affinities with binding constants of roughly 2 x 10(7) M(-1) and binding densities of 1 drug molecule per strand. The ACTD binding affinity for the corresponding heteroduplex obtained by annealing these two oligomers is, however, considerably reduced. Although spectroscopic results with related oligomers obtained by removing, replacing, or appending bases at the termini appear to be consistent with the end-stacking model, capillary electrophoretic (CE) evidence provides additional insights into the binding mode. CE experiments with the self-complementary oligomers d(CGAGCTCG) and d(CGTCGACG) revealed contrasting migration patterns in the presence of ACTD, with mobility retardation and acceleration exhibited by the GpC- and non-GpC-containing octamers, respectively, whereas the X/X-mismatched d(CGXCGXCG) experienced retardation. These results, along with those of related oligomers, suggest that ACTD may in fact stack at the duplex stem end of a monomeric hairpin or at the 3'-end of dG as a single strand. The seemingly cooperative ACTD binding and the curved Scatchard plot for the self-complementary d(CGTCGACG) may thus be attributed to the drug-induced duplex denaturation resulting from strong binding to single strands of d(CGXCGYCG) motif. Detailed structural information on the ACTD-DNA complexes, however, must await further NMR investigations.

Antibiotics, Antineoplastic↗
PubMed2000

Influence of portal hypertension on secretion of gastric mucus in rats.

OBJECTIVE: To assess the effect of portal hypertension on gastric adherent and soluble mucus in rats. DESIGN: Experimental study. SETTING: Teaching hospital, Taiwan. MATERIAL: 30 male Wistar rats. INTERVENTIONS: Portal hypertension was induced experimentally by partial ligation of the portal vein in 20 male Wistar rats: ten rats were examined after 4 weeks and the remaining 10 after 8. Another group of 10 rats (controls) had sham operations. MAIN OUTCOME MEASURES: Portal pressure, the severity of gross gastric mucosal lesions, and measurement of gastric adherent and soluble mucus. RESULTS: The portal pressure and the gross mucosal damage differed significantly between the experimental and the control groups (p < 0.01). There was significantly less gastric adherent mucus in the two experimental groups than in the control group (p = 0.002 and <0.001, respectively), whereas there was no significant differences in the amount of gastric soluble mucus (p = 0.5 and 0.1, respectively). The reduction in the gastric adherent mucus was closely related to the increase in portal pressure (p < 0.001) and the severity of portal hypertension-induced gastropathy (p < 0.001). CONCLUSIONS: Gastric adherent mucus may have an important role in the pathogenesis of portal hypertensive gastropathy, and its protective capacity is reduced by portal hypertension, as indicated by the decrease in gastric adherent mucus.

Animals↗
PubMed2000

The effect of the doctor-patient relationship on emergency department use among the elderly.

OBJECTIVES: This study sought to determine the rate of emergency department use among the elderly and examined whether that use is reduced if the patient has a principal-care physician. METHODS: The Health Care Financing Administration's National Claims History File was used to study emergency department use by Medicare patients older than 65 years in Washington State during 1994. RESULTS: A total of 18.1% of patients had 1 or more emergency department visits during the study year; the rate increased with age and illness severity. Patients with principal-care physicians were much less likely to use the emergency department for every category of disease severity. After case mix, Medicaid eligibility, and rural/urban residence were controlled for, the odds ratio for having any emergency department visit was 0.47 for patients with a generalist principal-care physician and 0.58 for patients with a specialist principal-care physician. CONCLUSIONS: The rate of emergency department use among the elderly is substantial, and most visits are for serious medical problems. The presence of a continuous relationship with a physician--regardless of specialty--may reduce emergency department use.

Aged↗
PubMed1999

DTaP vaccines from north american vaccine (NAVA): composition and critical parameters.

NAVA's acellular pertussis vaccine is based on highly purified pertussis toxin (PT) inactivated with H(2)O(2). PT was analysed using advanced biochemical methodology including mass spectroscopy (LC/MS), yielding mass and peptide mapping information on the subunits. Pertactin, adenylate cyclase, and Fim 1, 2 were below detection levels and only trace amounts of filamentous haemagglutinin (FHA) have been identified as a minor impurity. The vaccine does not induce anti-FHA antibodies during the course of a 3-dose primary immunization series in infants. B and T cell epitopes are preserved to a higher extent after H(2)O(2)detoxification when compared with chemical inactivation with formaldehyde, thus providing new information explaining why vaccines employing formaldehyde detoxified PT may need additional pertussis components added to induce high levels of protection. Anti-PT antibodies generated by NAVA diphtheria, tetanus, and acellular pertussis vaccine (DTaP) showed a positive correlation with protection against WHO-defined pertussis. The safety profiles for these vaccines showed low reactogenicity with no serious adverse events due to the vaccines.

Adult↗
PubMed1999

Self-aggregation of DNA oligomers with XGG trinucleotide repeats: kinetic and atomic force microscopy measurements.

Turbidity measurements via absorbance monitoring at 320 nm were employed to obtain autocatalytic-like kinetic profiles of K+-induced aggregate formation of d(XGG)4 and some related oligomers, where X = A, C, G, and T. At least 1 M KCl is needed to observe the turbidity-measurable aggregation at pH 8, and the relative propensity for aggregate formation is shown to follow the order d(GGG)4 > d(AGG)4 approximately d(TGG)4 >> d(CGG)4. The presence of Mg2+ greatly facilitates and dramatically reduces the amount of K+ required to initiate aggregation and significantly enhances the thermal stabilities of the aggregates. Replacement of K+ by Na+ fails to induce a similar phenomenon. The Psi-type CD characteristics of aggregates are strongly dependent on the sequence and ionic conditions. Despite their ease of aggregate formation, oligomers with AGG trinucleotide repeats fail to exhibit Psi-CD formation. The propensity for aggregation is greatly affected by the chain length, with oligomers of four repeats being most facile. Appending X base at the 3' end of d(GGXGGXGGXGG) appears to provide a greater hindrance to aggregation than at the 5' end. Atomic force microscopic images support some of these findings and reveal the morphologies of these aggregates. The presence of MgCl2 in solutions appears to considerably elongate the K+-induced aggregates.

Circular Dichroism↗
PubMed1999

Pathogenesis of early cardiac myocyte damage after severe burns.

BACKGROUND: The importance of early cardiac myocyte damage during postburn trauma has been emphasized in recent years. However, its pathogenesis, prevention, and treatment have not been fully clarified. The aim of this study is to define its pathogenesis. METHODS: Rats with 30% third-degree burns were used. Cardiac biochemical markers reflecting cardiac myocyte damage including troponin T, cardiac myosin light chain 1, creatinine kinase and its cardiac-specific isoenzyme compound, as well as inflammatory mediators such as tumor necrosis factor, endothelin/nitric oxide ratio, malondialdehyde, and superoxide dismutase, were determined. RESULTS: Cardiac biochemical markers reflecting cardiac myocyte damage, including troponin T, cardiac myosin light chain 1, cardiac-specific isoenzyme compound, were all significantly elevated between 3 hours and 24 hours after burn. Changes in tumor necrosis factor, endothelin/nitric oxide ratio, and malondialdehyde were similar to those of cardiac biochemical markers. In contrast, levels of superoxide dismutase declined markedly after burn. CONCLUSION: The findings of this study showed that considerable amounts of myocardial constructive protein degradation and release due to destruction of cardiac myocytes occurred early after severe burns. The inflammatory mediators released after burn injury may be involved in the pathogenesis of myocardial destruction.

Animals↗
PubMed1999

Secure placement of continuous ambulatory peritoneal dialysis catheters under laparoscopic assistance.

Laparoscopic surgical procedures were performed in 18 patients with end-stage renal disease for the placement of a Tenckhoff peritoneal dialysis catheter. Among them, 6 patients had received previous lower abdominal surgical treatment and 3 patients underwent laparoscopic rescue of dysfunctional Tenckhoff catheters. The operating time was between 40 and 80 minutes (median, 50 minutes). After a median follow-up period of 11 months, the short-term results revealed that no significant morbidity was associated with this procedure, and all catheters except two functioned well postoperatively. One of the catheters was not functional because of the patient's death, and the other one was removed because of persistent peritonitis. Laparoscopic secure placement of continuous ambulatory peritoneal dialysis catheters appears to be a simple, safe, and viable procedure, even in patients with previous lower-abdominal operations. The same technique can be used to rescue dysfunctional catheters that are displaced or obstructed by adhesion and omental wrapping, thus increasing catheter longevity.

Adult↗