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Biomedical subjects

F M Chen

Publications and source records attributed to F M Chen.

At least 37 records · Page 2Linked to original sources

Biochemical markers for assessment of bone metastases in patients with breast cancer.

Breast cancer commonly metastasizes to bones, producing both osteolytic and osteoblastic deposits. Different markers for quantitative determination of bone turnover have been developed to evaluate bone metastases of breast cancer. The urinary deoxypyridinoline (Dpd), a crosslink product of collagen molecules found in bone and excreted in urine during bone degradation, and bone specific alkaline phosphatase (B-ALP), an isoenzyme localized in the membrane of osteoblasts and released in circulation during bone formation, were recently described as a group of markers of bone turnover in metastatic cancer. The urinary Dpd/creatinine (Cre) ratios and the serum B-ALP activity were determined in the samples from 148 patients who suffered from breast cancer (BC patients) with or without bone metastases, and 42 healthy women. For comparison, other biochemical markers, e.g. carcinoembryonic antigen (CEA), CA15-3, tissue polypeptide antigen (TPA), tissue polypeptide specific antigen (TPSA), and total alkaline phosphatase (T-ALP) in these samples were also evaluated. The results showed that there was a significant difference in urinary Dpd/Cre ratio between the control group and the patients with breast cancer (BC group) (mean +/- S.D., 5.69 +/- 1.26 vs. 8.19 +/- 3.95 nM/mM, P < 0.05). However, there was no significant difference between their B-ALP activities in the two groups. In addition, the BC patients with bone metastases showed elevated urinary Dpd/Cre ratios and B-ALP activities and ratios of (Dpd/Cre)/B-ALP in compare with BC patients without bone metastases (P < 0.05). Meanwhile, the urinary Dpd/Cre ratios (10.50 +/- 5.04 nmol/mmol) in the advanced stage of BC patients were higher than those in an early stage (7.45 +/- 3.23 nmol/mmol) (P < 0.05), but their serum B-ALP activities increased only in stage IV (P < 0.05). The urinary Dpd/Cre ratios also increased progressively according to the degree of bone metastases (P < 0.05), but their serum B-ALP activities only increased in severe bone metastases (P < 0.05). The results showed that the increase of a bone osteolytic activity took place earlier than that of a bone osteoblastic activity in the metastatic BC patients. In compare with other conventional markers, the best diagnostic efficiency of biochemical markers, analyzed by step wise discriminate analysis, was provided by CEA followed by Dpd/Cre ratio, CA15-3, TPA, TPSA, B-ALP and T-ALP. We conclude that showed the urinary Dpd/Cre ratio was a useful tumor marker to evaluate breast cancer with bone metastases.

Adult↗

Mondor's disease in the breast.

Mondor's disease, superficial thrombophebitis of the breast, is an uncommon self-limiting condition. Surgical procedures and trauma were the common known causes. The objective of this study was to evaluate the incidence of Mondor's disease in different breast operations in lower risk of breast cancer area over a 6-year period and to identify its causes, clinical features, related surgical factors and associated breast cancer. Eighty-four cases of Mondor's disease were obtained from 9657 new patients in the breast clinic of Kaohsiung Medical University Hospital between January 1991 and December 1996. The incidence per year was close (0.84%-0.96%) although the number has been increasing each year. In 23 cases, no definite cause was diagnosed, whereas in 61 cases, the disorder was secondary because the pathogenesis could be discerned. The identified causes included forty-three cases caused by breast surgery, two cases associated with breast cancer and sixteen cases with other benign causes. Although the incidence did not differ significantly between breast surgery (0.95%) and non-surgical causes (0.79%), the highest incidence, 1.52%, occurred when excision through circumareolar incision and tunnel procedure for cosmesis (25 cases in 1634 excisions) were used, and the lowest 0.69% when excisions through direct incision (14 cases in 2004 excisions) were performed. (P < 0.05) The other incidence rates were 1.56% in breast conserving surgery which is higher than 0.37% following mastectomy. The incidence of the disease was higher (4.28%) when the distance of the breast lesion was more than 3 cm from the areolar edge, compared to 1.20% for the 2 cm group and 0.32% for the 1 cm group (P < 0.05) in tunnel procedures. The incidence of Mondor's disease during breast surgery was not significantly different in different breast quardrants. Although Mondor's disease is a benign, self-limiting condition, a high incidence developed in the excision biopsy through circumareolar incision with tunnel procedure when the distance from the breast lesion to the areolar edge was more than 3 cm. To prevent this complication, the tunnel procedure in breast biopsy should be avoided. The incidence of Mondor's disease associated with breast cancer was low (2.4%) in the lower-incidence breast cancer area from this series, but awareness of the condition is recommended.

Adolescent↗

Geocoding and linking data from population-based surveillance and the US Census to evaluate the impact of median household income on the epidemiology of invasive Streptococcus pneumoniae infections.

The emergence of drug-resistant Streptococcus pneumoniae poses new clinical challenges and may also reflect a change in the epidemiology of S. pneumoniae infections. A variety of studies have shown that drug-resistant S. pneumoniae infections are linked to antimicrobial use. It has been hypothesized that persons of high socioeconomic status are at increased risk for a drug-resistant infection because of greater access to antimicrobial drugs. To assess whether median household income is associated with increased risk of penicillin-nonsusceptible S. pneumoniae infections, the authors geocoded and linked data from population-based surveillance for invasive pneumococcal disease with data from the 1990 US Census. Among invasive pneumococcal isolates from Atlanta, Georgia, in 1994, increasing proportions of penicillin-nonsusceptible isolates were associated with higher median household incomes (chi2 for trend, 15.17; p=0.002). Despite higher rates of invasive pneumococcal disease among blacks and persons who resided within lower median household income areas, white patients in areas with higher median household income had a higher risk of being infected with strains that were not susceptible to penicillin (Wilcoxon rank sum, Z=2.66, p=0.008). These findings demonstrated the utility of geocoding and US Census data in describing the epidemiology of drug-resistant S. pneumoniae and also provided more evidence that socioeconomic factors may influence the development of drug resistance.

Adolescent↗

Circular dichroic and kinetic differentiation of DNA binding modes of distamycin.

DNA binding modes of distamycin (DST) were investigated via comparative binding studies with oligomeric duplexes of the form d(GCG-X-GCG).d(CGC-Y-CGC), where Y is complementary to X and X = 4- or 5-base binding site. It was found that 1:1 and 2:1 drug-duplex complexes exhibit distinctly different circular dichroic (CD) spectral characteristics and can, thus, serve as diagnostic tools for binding mode differentiation. CD intensity profiles at 265 or 275 nm as a function of drug to DNA ratios can reveal the extent of binding cooperativity for 2:1 complex formation (i.e., the relative binding affinities of 2:1 vs 1:1) at a 5-base-paired binding site. Comparison of these profiles leads to the following qualitative ranking for the binding cooperativity for the studied sites: AAGTT, ATATA >/= AAACT > AATAA, AAATA, AAAGT > AATAT > TAAAA >/= AAATT >/= AAAAA >/= ATAAA, AAAAT. The plausibility of this ordering is strengthened by its agreement with the ranking established by earlier NMR studies on some of the sequences. The significantly slower DST dissociation kinetics of the 2:1 complexes as compared to those of 1:1 made the kinetic measurements of SDS-induced dissociation by the stopped-flow technique possible. The results indicate that the AAGTT site exhibits the slowest DST dissociation rate, with a characteristic time of 35 s. The rates of dissociation in general correlate reasonably well with the cooperativity order found via equilibrium CD measurements (the higher the binding cooperativity, the slower the rate of dissociation). Base sequence specific binding of DST was also found for the 1:1 complex formation at the 4-base-paired sites, with AAAA, TTTT, ATTT, and AAAT sequences exhibiting the highest binding affinities.

Antiviral Agents↗

Binding of actinomycin D to DNA oligomers of CXG trinucleotide repeats.

Actinomycin D (ACTD) binding propensities of DNA with CXG trinucleotide repeats were investigated using oligomers of the form d[AT(CXG)n = 2-4AT] and their corresponding heteroduplexes, where X = A, C, G, or T. These oligonucleotides contain -CXGCXG-, -CXGCXGCXG-, and -CXGCXGCXGCXG- units that can form homoduplexes containing one, two, and three GpC binding sites, respectively, with flanking X/X mismatches. The corresponding heteroduplexes contain these same sites with flanking Watson-Crick base pairs. It was found that oligomers with X = G exhibit weak ACTD affinities whereas those with X not equal to G and n = 3 exhibit unusually strong ACTD binding affinities with binding constants ranging from 2.3 x 10(7) to 3.3 x 10(7) M-1 and binding densities of approximately 1 drug molecule/strand (or 2/duplex). These binding affinities are considerably higher than those of their shorter and longer counterparts and are about 2- and 10-fold stronger than the corresponding CAG.CTG and CGG.CCG heteroduplexes, respectively. The CTG-containing oligomer d[AT(CTG)3AT] stands out as unique in having its ACTD dissociation kinetics being dominated by a strikingly slow process with a characteristic time of 205 min at 20 degrees C, which is 100-fold slower than d[AT(CAG)3AT], nearly 10-fold slower than the corresponding heteroduplex, and considerably slower than d[AT(CTG)2AT] (63 min) and d[AT(CTG)4AT] (16 min). The faster dissociation rate of the n = 4 oligomer compared to its n = 2 counterpart is in apparent contrast with the observed 10-fold stronger ACTD binding affinity of the former. It was also found that d[AT(CCG)3AT] exhibits the slowest dissociation rate of the CGG/CCG series, being more than an order of magnitude slower than that of its heteroduplex (tau slow of 43 vs 2 min). The finding that a homoduplex d[AT-CXG-CXG-CXG-AT]2 can bind two ACTD molecules tightly is significant since it was thought unlikely for two consecutive GpC sites separated by a single T/T mismatch to do so.

Base Composition↗

Serial experimental and clinical studies on the pathogenesis of multiple organ dysfunction syndrome (MODS) in severe burns.

These serial clinical and experimental studies were designed to clarify the pathogenesis of postburn MODS. Both animal and clinical studies were performed. In animal experiments, 46 male cross-bred dogs were cannulated with Swan-Ganz catheters and 39 of them were inflicted with 50% TBSA third degree burns (7 were used as controls). The burned dogs were randomly divided into 4 groups: immediate infusion, delayed infusion, delayed fast infusion and delayed fast infusion combined with ginsenosides. All dogs were kept under constant barbiturate sedation during the whole study period. Hemodynamics, visceral MDA, mitochondrial respiratory control rate (RCR) and ADP/O ratio, ATP, succinic dehydrogenase (SDH), organ water content as well as light and electron microscopy of visceral tissues were determined. In the clinical study, 61 patients with extensive deep burns were chosen, of which 16 sustained MODS. Plasma TXB2/6-keto-PGF1alpha ratio, TNF, SOD, MDA, circulatory platelet aggregate ratio (CPAR), PGE2, interleukin-1, total organ water content and pathological observations of visceral tissues from patients who died of MODS were carried out. Results demonstrated that ischemic-reperfusion damage due to severe shock, sepsis and inhalation injury are three main causes of postburn death. All inflammatory mediators increased markedly in both animals and patients who sustained organ damage or MODS. SDH, RCR, ADP/O and ATP decreased significantly. These findings suggested that ischemic damage and systemic inflammatory response syndrome (SIRS) initiated by mediators or cytokines might be important in the pathogenesis of postburn MODS.

6-Ketoprostaglandin F1 alpha↗

Detection of chlamydiosis in a shipment of pet birds, leading to recognition of an outbreak of clinically mild psittacosis in humans.

Avian chlamydiosis was detected in a shipment of > 700 pet birds from a Florida bird distributor that were sold to nine Atlanta-area pet stores in August 1995. Respiratory illness among persons who had recently acquired birds from this shipment was reported to local public health officials. The attack rate of acute respiratory illness was 10.7% among persons in households exposed to birds from the implicated flock vs. 1.8% among control households (odds ratio, 6.60; 95% confidence interval, 1.39-31.2). Illness and serological evidence of infection in the absence of symptoms were more common among persons in households with recently purchased birds that were sick or that had died and among persons who had had direct contact with the birds. Clinical psittacosis or serological evidence of Chlamydia psittaci infection was found in 30.7% of households with birds from the infected flock. Mild illnesses and asymptomatic infections in exposed persons were unusual features of this outbreak.

Animals↗

Gastric duplication cyst: report of a case.

Gastric duplication cyst is a rare disease entity, especially in the adult population. We report a case of 33-year-old female patient who presented with epigastric pain, postprandial fullness and nausea for the past several months. Gastroendoscopy showed a submucosal mass with normal overlying gastric mucosa. Upper gastrointestinal series confirmed a extrinsic compression of mass in the fundus of the stomach. Endoscopic ultrasonography and computerized tomography demonstrated the lesion to be a cyst in nature. The surgical procedure consisted of total excision without violation of the gastric lumen. Gastric mucosa was found by the histologic study of the excised cyst.

Adult↗

Molecular epidemiology of bartonella infections in patients with bacillary angiomatosis-peliosis.

BACKGROUND: Bacillary angiomatosis and bacillary peliosis are vascular proliferative manifestations of infection with species of the genus bartonella that occur predominantly in patients infected with the human immunodeficiency virus. Two species, B. henselae and B. quintana, have been associated with bacillary angiomatosis, but culture and speciation are difficult, and there has been little systematic evaluation of the species-specific disease characteristics. We studied 49 patients seen over eight years who were infected with bartonella species identified by molecular techniques and who had clinical lesions consistent with bacillary angiomatosis-peliosis. METHODS: In this case-control study, a standardized questionnaire about exposures was administered to patients with bacillary angiomatosis-peliosis and to 96 matched controls. The infecting bartonella species were determined by molecular techniques. RESULTS: Of the 49 patients with bacillary angiomatosis-peliosis, 26 (53 percent) were infected with B. henselae and 23 (47 percent) with B. quintana. Subcutaneous and lytic bone lesions were strongly associated with B. quintana, whereas peliosis hepatis was associated exclusively with B. henselae. Patients with B. henselae infection were identified throughout the study period and were epidemiologically linked to cat and flea exposure (P< or =0.004), whereas those with B. quintana were clustered and were characterized by low income (P=0.003), homelessness (P = 0.004), and exposure to lice (P= 0.03). Prior treatment with macrolide antibiotics appeared to be protective against infection with either species. CONCLUSIONS: B. henselae and B. quintana, the organisms that cause bacillary angiomatosis-peliosis, are associated with different epidemiologic risk factors and with predilections for involvement of different organs.

Angiomatosis, Bacillary↗

Supramolecular self-assembly of d(TGG)4, synergistic effects of K+ and Mg2+.

Spectral evidence indicates that molar concentrations of K+ can induce aggregate formation in d(TGG)4. The 320-nm turbidity monitoring indicates that more than 1 M KCl is needed for the onset of aggregation to occur at 20 degrees C within the time span of 24 h. The kinetic profile is reminiscent of autocatalytic reactions that consist of a lag period followed by accelerative and levelling phases. Progressive shortening of lag periods and more rapid accelerative phases accompany further increases in [K+]. Interestingly, the presence of Mg2+ greatly facilitates the aggregate formation and results in the prominent appearance of an intense psi-type CD. For example, whereas 1 M K+ fails to induce aggregate formation of d(TGG)4 within 24 h, the addition of 1 mM Mg2+ to a 1 M K+ solution is sufficient to induce the onset of aggregation in approximately 12 h. Furthermore, adjustment of the buffer to 16 mM Mg2+/1 M KCl reduces the lag time to less than 10 min and aggregation is nearly complete in 2 h. The requirement of [K+] for aggregation is reduced to 2 mM in the presence of 16 mM Mg2+, a reduction of nearly three orders of magnitude when compared to solutions without Mg2+. The effects of K+ and Mg2+ ions are synergistic, because the presence of 16 mM Mg2+ alone does not induce aggregate formation in this oligomer. Thermal stabilities of the aggregates are strongly dependent on the concentrations of these two ions. Although aggregates formed in the presence of 2 M KCl alone melt around 55 degrees C, those formed with added 16 mM Mg2+ melt at approximately 90 degrees C, with some aggregates remaining unmelted even at 95 degrees C. The slow kinetics of aggregate formation led to the appearance of gross hystereses in the cooling profiles. The interplay of these two ions appears to be specific, because the replacement of K+ by Na+ or the replacement of Mg2+ by other divalent cations does not lead to the observed self-assembly phenomenon, although Sr2+ can substitute for K+. A possible mechanism for the formation of self-assembled structures is suggested.

Base Sequence↗

The arc index in evaluation of Class III malocclusion.

Lateral cephalometric radiographs were obtained for 46 individuals (18 men and 28 women) aged 20 to 30 years. The sample consisted of Taiwanese with Class III malocclusions and prognathic facial profiles. A modification of the Sassouni arch analysis was used to evaluate this group. All parameters were compared with the norms for adult Taiwanese. The facial pattern of the Class III group was similar to that reported in other studies. The maxilla was in a retrusive position; the lengths of the maxilla and the mandible were significantly different from those in the normal group; the mandibular central incisor was retroinclined; and the total gonial angle, upper gonial angle, and lower gonial angle in the Class III group were significantly different from those angles in the normal group in both sexes. The arc index represented the maxillomandibular positional relationship. There was a statistically significant difference between the mean arc indexes of the Class III and the normal groups. The results indicated that the more negative the arc index, the greater the Class III tendency.

Adult↗

Actinomycin D binds strongly and dissociates slowly at the dGpdC site with flanking T/T mismatches.

Comparative electrophoretic, thermal denaturation, and spectroscopic studies with dodecamers of the form d(ATTA-XGCX-TAAT) and their self-complementary counterparts suggest that actinomycin D (ACTD) binds strongly to a 5'GC3' site with flanking T/T mismatches and moderately to that with C/C mismatches but weakly to those with other G/G or A/A mismatches. The relative binding order is found to be T/T > C/C > G/G > A/A. The ACTD binding affinity for the GC site with T/T mismatches is comparable to the strong binding of self-complementary-XGCY-sequences. Both the ACTD association and dissociation kinetics at the GC site with flanking T/T mismatches require two-exponential fits. The slow component of the association rates is slower than those of the self-complementary sequences, whereas that of the dissociation is only slightly faster than that of the -TGCA- sequence. Interestingly, the slow component of dissociation is decidedly slower than those of -AGCT- and -CGCG- sites and is more than an order of magnitude slower than those with C/C, G/G, and A/A mismatches. These kinetic results are further corroborated by fluorescence measurements using 7-amino-ACTD, a fluorescent analog of ACTD. In addition, fluorescence and absorbance spectral characteristics indicate that the binding mode at the GC site with flanking T/T mismatches resembles those of strong-binding self-complementary -XGCY- sites which are known to be intercalative in nature. The observed slow ACTD dissociation at the T/T-mismatched site suggests that the minor-groove environment near the T/T-mismatched pairs provides favorable interactions with the pentapeptide rings of the drug, whereas the others, especially those of bulkier purine/purine mismatches, result in less favorable interactions.

Base Composition↗

Is the strong actinomycin D binding of d(5'CGTCGACG3') the consequence of end-stacking?

It has been reported that ACTD binds strongly and cooperatively to a non-GC containing self-complementary octamer d(CGTCGACG) with a 2:1 drug to duplex ratio (Synder et al., 1989). If one views the classic intercalative preference of ACTD for the 5'GpC3' sequence to be the drug favoring the 3'-side of dG, the possibility exists that the drug molecules may in fact stack on the G.C base pairs at both ends of this oligomeric duplex. To investigate this possibility, d(CGTCGACG) and several related oligomers resulting from replacing the terminal base(s) or appending with dT and/or dA are used in a comparative study employing equilibrium titration, thermal denaturation, kinetic, and various spectral measurements. Absorbance titrations at 20 degrees C confirm the strong and highly cooperative nature of ACTD binding to this octamer. The stoichiometric association constants for the binding of the first and second drugs were found to be 1 x 10(5) and 3.2 x 10(7) M-1, respectively. The base replacements of dG and dC at the respective ends resulted in a much weaker ACTD binding affinity, the loss of binding cooperativity, and much faster association and dissociation kinetics. These are consistent with the inability of the drug to stack on the 3'-side of dG due to base replacements. Appending the end(s) with dA and/or dT resulted in some diminution of binding affinity and cooperativity, appearance of slower association kinetic components, and unusually strong 7-amino-ACTD fluorescence enhancement for oligomers with dA or dT attached to dG at the 3'-terminal. To further support our postulate, studies were also made with d(CGACGTCG), which is related to the parent octamer by inverting the A.T pairs. It was found that, despite the altered internal sequence, this oligomer exhibits cooperative ACTD binding and kinetic characteristics very similar to those of the parent octamer, consistent with its ability to end-stack on the 3'-side of dG.

Antibiotics, Antineoplastic↗

The morphologic structure of the openbite in adult Taiwanese.

Anterior openbite (AOB) is an intricate occlusal problem. Treatment of AOB is one of the most challenging tasks in orthodontics. An ethnic-specific norm for craniofacial skeletal patterns would be valuable in diagnosing and treating patients with AOB. To establish this norm for the people of Taiwan, a cephalometric study was conducted using the quadrilateral analysis developed by DiPaolo. The sample consisted of 15 males and 25 females in their 20s and 30s. The patients were randomly selected and were diagnosed with AOB. Various craniofacial skeletal patterns were measured, and these measurements were compared with values taken from a group of normal Taiwanese as well as with published values from a hyperdivergent group of westerners. The results support the following generalizations: (1) The growth pattern of subjects in the AOB group is hyperdivergent. (2) Both the maxillary and mandibular corpora of subjects with AOB are shorter than those of normal subjects. (3) The sagittal angle, average lower facial height, and the maxillary and mandibular sagittal ratio of subjects with AOB are larger than those of normal subjects. Abnormalities in the maxillomandibular complex causing changes in the vertical dimension of facial patterns are involved in AOB.

Adult↗

Acid-facilitated supramolecular assembly of G-quadruplexes in d(CGG)4.

Molar [K+] induces aggregate formation in d(CGG)4, as evidenced by absorbance, circular dichroic (CD), and gel measurements. The kinetics of this transformation are extremely slow at pH 8 but are found to be greatly facilitated in acidic conditions. Kinetic profiles via absorbance or CD monitoring at single wavelength resemble those of autocatalytic reacting systems with characteristic induction periods. More than 0.8 M KCl is needed to observe the onset of aggregation at 20 degrees C and pH 5.4 within the time span of 1 day. Time-dependent CD spectral characteristics indicate the formation of parallel G-tetraplexes prior to the onset of aggregation. Despite the evidence of K(+)-induced parallel G-quadruplex and higher molecular weight complex formation, both d(TGG)4 and d(CGG)4T fail to exhibit the observed phenomenon, thus strongly implicating the crucial roles played by the terminal G and base protonation of cytosines. A plausible mechanism for the formation of a novel self-assembled structure is speculated. Aided by the C+.C base pair formation, parallel quadruplexes are initially formed and subsequently converted to quadruplexes with contiguous G-tetrads and looped-out cytosines due to high [K+]. These quadruplexes then vertically stack as well as horizontally expand via interquadruplex C+.C base pairing to result in dendrimer-type self-assembled super structures.

Base Composition↗

N,N-dialkoxycarbonylamino acids from the sodium hydride-mediated reaction of alkyl chloroformates with mixed anhydrides of N-alkoxycarbonylamino acids.

Reaction of mixed anhydride R1OCO-NHCHR2-CO-O-COOR3 for R1 = benzyl and tert-butyl and R3 = methyl, ethyl, benzyl and allyl with sodium hydride and R3OCOCl followed by acid hydrolysis gives modest yields of R1OCO-N(R3OCO)CHR2-COOH. The products are contaminated by parent acid R1OCO-NHCHR2-COOH that is not readily removed. About 75% of the acylation originates from intramolecular transfer of the alkyl carbonate moiety; the remainder comes from acylation by the alkyl chloroformate.

Amino Acids↗