Biomedical subjects

C J Huang

Publications and source records attributed to C J Huang.

At least 55 records · Page 3Linked to original sources

PubMed2000

Analysis of relative binding affinity of E7-pRB of human papillomavirus 16 clinical variants using the yeast two-hybrid system.

A number of genotypes of the human papillomaviruses (HPV) are associated with malignancies of the uterine cervix. Sequencing work has revealed the existence of intratype HPV variants with minor differences in the nucleotide sequence. More recent data suggest the possibility that some of the variants may have different modes of clinical manifestation. In this study, sequences of the E6 and E7 oncogenes of 17 HPV16 isolates derived from PAP smear samples of Taiwanese patients were analyzed. A number of E6 and E7 novel variants were found. Particularly, a prevalent (64.7%) E6 polymorphic site A442C with an E113D amino acid substitution seems specific to Taiwanese patients. In E7, two novel but silent polymorphic sites G663A (41.2%) and T846C (88.2%) were also prevalent in the samples analyzed. The yeast two-hybrid system was adopted for rapid assessment of relative E7-pRb binding affinity in the variants. The relative binding affinities of the E7 proteins of different HPV types to pRB were in close agreement with previous biochemical data. A T663G/C24W polymorphic change in E7 correlated with a decrease in E7-pRb relative binding affinity the significance of which remains to be clarified. This semi-quantitative biochemical and genetic approach may be useful as a first step in the development of clinical protocols for the screening and identification of important HPV variants for clinical interpretation and for further functional analysis by transfection or other bioassays.

Female↗

PubMed2000

Comparison of inhalation induction with 2%, 4%, 6%, and 8% sevoflurane in nitrous oxide for pediatric patients.

BACKGROUND: Sevoflurane is almost the idealest volatile anesthetic agent regarding inhalation induction of general anesthesia. Previous studies have established a role of sevoflurane in high concentration primed in the circuit for inhalation induction in pediatric patients. However, which concentration of sevoflurane is suitable has not yet been reported. This study was designed to compare the efficiency of different concentration of sevoflurane i.e. 2%, 4%, 6%, and 8% and with N2O in 50% oxygen for induction of anesthesia in pediatric patients and at the same time to evaluate the tolerance of patients. METHODS: One hundred and twenty children who were 3 to 10 years old, of ASA class I, were randomly assigned to receive either 2%, 4%, 6%, and 8% sevoflurane and N2O in 50% O2 for induction of anesthesia. The time to loss of eyelash reflex, responses of airway reflex, involuntary movement, and hemodynamic responses were recorded. RESULTS: Ninety-nine children completed the study. The times to loss of eyelash reflex with 2% in sequence to 8% sevoflurane were 114 +/- 21 s, 87 +/- 11 s, 75 +/- 6 s, and 48 +/- 8 s respectively. Incidence of airway reflex response including coughing, laryngospasm, and breath holding was the highest in the 8% group (P < 0.05). Inhalation induction with sevoflurane significantly decreased systolic as well as diastolic blood pressure compared with baseline blood pressure in all the four groups. The extent of decrease of blood pressure was within 20% range of baseline blood pressure in all groups. Significant increase of heart rate was only observed in the 4% and 6% groups. CONCLUSIONS: Sevoflurane 6% for inhalation induction apparently caused low incidence of adverse effects and hastened induction. We suggest that 6% sevoflurene is a concentration more practical for inhalation induction in pediatric patients.

Anesthetics, Inhalation↗

PubMed1999

Identification and gene structure of a novel human PLZF-related transcription factor gene, TZFP.

A novel cDNA clone was identified through yeast two-hybrid experiments. Following cross-examination between the cDNA clones, EST clones, and the cosmid clone, we could digitally assemble a new zinc finger transcription factor gene. This predicted gene has a cDNA size of about 1960 bp and is translated into a 487-amino-acid protein. According to database analysis, this gene contains three C2H2 zinc finger motifs and is highly related to human PLZF (promyelocytic leukemia zinc finger protein). The full-length coding region of the gene was isolated, and its sequences were confirmed by DNA sequencing. Interestingly, one splicing variant lacking exon III was also identified. Northern blot analysis revealed that this gene is mainly expressed in human testis. In conclusion, we have identified a new member of the PLZF zinc finger protein family, the testis zinc finger protein (TZFP), which is mainly expressed in testis tissue.

Amino Acid Sequence↗

PubMed1999

Genomic organization of the Oreochromis mossambicus glutamate receptor subunit 2 beta gene (fGluR2 beta): presence of two different 5'-untranslated regions.

The AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid)-preferring receptor is one of the pharmacologically defined ionotropic glutamate receptors, which mediate fast excitatory synaptic transmission in the central nervous system of vertebrates. Here, we report the mapping of the transcriptional start points and identification of the intron-exon boundaries of the teleost AMPA receptor subunit gene fGluR2 beta. fGluR2 beta and the mouse GluR2 share a similar genomic organization, having identical intron insertion sites and a large intron 2; however, fGluR2 beta has an extra exon encoding an alternate 5'-UTR. Results of RT-PCR and RNase protection analyses indicate that mature fish brain expresses two types of fGluR2 beta transcripts with different 5' ends. Transcriptions of these two fGluR2 beta transcripts started from two chromosomal regions separated by at least 10 kb. Only the transcript starting from the region more upstream on the chromosome was spliced. Moreover, transcript initiated from the downstream region was more abundant than that initiated from the upstream region.

5' Untranslated Regions↗

PubMed1999

Two distinct c-ski cDNAs of fish, tilapia (Oreochromis aurea).

Two classes of tilapia c-ski cDNA (accession nos. AJ012011, AJ012012), designated as tski1 and tski2, respectively encoded a 687 and a 714 AA protein and shared a 57% AA identity. Comparison with the Ski proteins of chickens, humans and Xenopus, tilapia TSki polypeptides shared a 60, 57, and 57% (TSki1) and 67, 63, and 61% (TSki2) AA identity, respectively. The most and the least abundant c-ski mRNAs are located in the brain and the skeletal muscle, respectively. Both tski1 and tski2 were widely expressed in the adult tissues examined, but tski2 transcripts were at higher levels except in the ovary and oocytes: tski1 transcripts were predominant in the ovary, whereas tski2 transcripts were predominant in the testes. In the oocytes, the tski1 mRNA was a maternally-inherited stockpile that subsequently was degraded, so that the expression ratio of tski1 to tski2 transcripts declined gradually as the fish developed from oocyte to 4-cm fry. Mol. Reprod. Dev. 54:223- 231.

Amino Acid Sequence↗

PubMed1999

Acute effects of thyroid hormone analogs on sodium currents in neonatal rat myocytes.

We previously reported that T3(3,3',5-triiodo-L-thyronine) acutely increases sodium currents (INa) in neonatal rat myocytes. Here we compare the effects of several thyroid hormone analogs, including T4(3,3',5,5'-tetraiodo-L-thyronine), rT3(3,3',5'-triiodo-L-thyronine), D-T3(3,3',5-triiodo-D-thyronine), 3,5-T2(3,5-diiodo-L-thyronine), DIT (3,5-diiodo-L-tyrosine), MIT (3-monoiodo-L-tyrosine), tetrac (3,3',5,5'-tetraiodo-thyroacetic acid), triac (3, 3',5-triiodo-thyroacetic acid), and tyrosine, on INa in cultured neonatal rat myocytes (n ranged from 9 to 28 for each comparison). T4, T3, 3,5-T2, and DIT (10 n m) all increased current density relative to control to a similar degree: to 1.22+/-0.2, 1.21+/-0.03, 1.16+/-0.02 and 1.16+/-0.03, respectively, P<0.05. In contrast, thyroid hormone analogs with an altered side group of the inner iodophenyl ring, including tetrac, triac, and D-T3, had no effect on INa nor did rT3, MIT or tyrosine. Pretreatment with rT3 inhibited the effects of T4, T3, 3,5-T2, and DIT. Conversely, the dose-dependent inhibitory effect of amiodarone, an iodinated benzofuran derivative that antagonizes thyroid hormone actions, on INa was blocked when myocytes were pretreated with T3(100 n m, n=3), suggesting an interaction of T3 with amiodarone. The enhancement of INa by T3 and 3, 5-T2 could not be blocked by propranolol, suggesting that the effects are not mediated through beta -adrenergic signaling pathways. In conclusion, the present results suggest that the acute effects of thyroid hormone and analogs on cardiac INa are mediated by a non-genomic thyroid hormone receptor with a unique structure-activity relationship.

Adrenergic beta-Antagonists↗

PubMed1999

Benefits of endorectal ultrasound for management of smooth-muscle tumor of the rectum: report of three cases.

Smooth-muscle tumor of the rectum is rare, and the therapeutic strategy is still controversial. Endorectal ultrasound was used to evaluate three patients with smooth-muscle tumor of the rectum. Endorectal ultrasound demonstrated a homogenous hypoechoic tumor without invasion to the perirectal tissue in two patients. The tumor was 5 cm in diameter in one patient and 4 cm in diameter in the other patient, and they were excised locally. Their histologic types were leiomyoma and leiomyosarcoma. The third patient had a recurrent leiomyosarcoma. Proctosigmoidoscopy found a linear lesion with ulcerated mucosa on the rectal wall. Endorectal ultrasound observed a hypoechoic solid tumor of 3.5 cm x 1 cm, which involved the mucosal, submucosal, and muscle layers of the rectal wall. Disruption of the first hypoechoic layer was identified. Abdominoperineal resection was performed. Endorectal ultrasound follow-up revealed no evidence of recurrence in any of these patients. Endorectal ultrasound can help to define the extent of disease and may be a useful adjunct in deciding about the appropriate surgical procedure in these diseases.

Adult↗

PubMed1999

In vitro diffusion of lidocaine across endotracheal tube cuffs.

PURPOSE: Lidocaine diffuses across endotracheal tube cuffs, which may serve as a reservoir for local anesthetic to assist in the prevention of ETT-induced cough while emerging from general anesthesia. However, the rate of diffusion is slow. Two techniques, alkalization and warming, may increase the proportion of uncharged drug available for diffusion. The purpose of this study is to determine the effectiveness of warming alkalization or warming with alkalization on diffusion. METHODS: Four preparations of lidocaine 4% were studied. Group (Gr) L-lidocaine (24 degrees C), Gr WL--warmed lidocaine (38 degrees C), Gr AL--alkalized lidocaine (24 degrees C), Gr WAL--warmed, alkalized lidocaine (38 degrees C). Twenty-four Mallinckrodt 8.0 ID (Mallinckrodt Critical Care Division of Mallinckrodt, Inc., Glens Falls, New York) endotracheal tube cuffs were filled with 6 ml of one of the four preparations. They were then placed in a 20 ml water bath at 38 degrees C and samples were drawn from the water bath at intervals for up to 360 min. The lidocaine concentration in each sample was determined by gas chromatography. RESULTS: The highest lidocaine concentration was reached in Gr WAL (410.98 +/- 8.53 micrograms.ml-1) after 300 min and then decreased to 376.18 +/- 4.59 micrograms.ml-1 after 360 min. In Gr AL the highest concentration (235.05 +/- 2.99 micrograms.ml-1) was reached after 360 min. Lidocaine concentrations in Gr L and WL after 360 min were 3.19 +/- 1.16 micrograms.ml-1 and 4.32 +/- 2.02 micrograms.ml-1 respectively. CONCLUSION: Alkalization with or without warming, but not warming alone, promotes lidocaine diffusion from endotracheal tube cuff.

Alkalies↗

PubMed1999

Transferrin is an essential factor for myelination.

It has been established that oligodendrocytes, the myelin forming cells, participate in iron homeostasis through the synthesis and secretion of transferrin. Here we investigated whether a correlation exists between myelination, the commonly studied function of oligodendrocytes, and that of transferrin synthesis and secretion. We used a proteolipid protein mutant, the myelin deficient rat, whose condition is characterized by severe hypomyelination. We compared the ontogenic profile for transferrin gene expression in mutants with that of unaffected rat pups through northern blot analysis and in situ hybridization. Surprisingly, transferrin synthesis was null in mutant oligodendrocytes. Next, we demonstrated that a single apo-transferrin intraparenchymal injection administered to P5 rat pups enabled mutant oligodendrocytes to synthesize myelin basic protein and to myelinate axons, indicating that transferrin effects mutant oligodendrocyte maturation regardless of its source. Thus, transferrin availability is essential for oligodendrocyte maturation and function, and oligodendrocytes are most vulnerable to transferrin deficiency during the premyelinating stage.

Animals↗

PubMed1999

Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor.

1. Flavonoids display a wide range of pharmacological properties including anti-inflammatory. Anti-mutagenic, anti-carcinogenic and anti-cancer effects. Here, we evaluated the effects of eight flavonoids on the tumour cell proliferation, cellular protein phosphorylation, and matrix metalloproteinase (MMPs) secretion. 2. Of the flavonoids examined, luteolin (Lu) and quercetin (Qu) were the two most potent agents, and significantly inhibited A431 cell proliferation with IC50 values of 19 and 21 micronM, respectively. 3. The epidermal growth factor (EGF) (10 nM) promoted growth of A431 cells (+25+/-4.6%) and mediated epidermal growth factor receptor (EGFR) tyrosine kinase activity and autophosphorylation of EGFR were inhibited by Lu and Qu. At concentration of 20 micronM, both Lu and Qu markedly decreased the levels of phosphorylation of A431 cellular proteins, including EGFR. 4. A431 cells treated with Lu or Qu exhibited protuberant cytoplasmic blebs and progressive shrinkage morphology. Lu and Qu also time-dependently induced the appearance of a ladder pattern of DNA fragmentation, and this effect was abolished by EGF treatment. 5. The addition of EGF only marginally diminished the inhibitory effect of luteolin and quercetin on the growth rate of A431 cells, treatment of cellular proteins with EGF and luteolin or quercetin greatly reduced protein phosphorylation, indicating Lu and Qu may act effectively to inhibit a wide range of protein kinases, including EGFR tyrosine kinase. 6. EGF increased the levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), while Lu and Qu appeared to suppress the secretion of these two MMPs in A431 cells. 7. Examination of the relationship between the chemical structure and inhibitory effects of eight flavonoids reveal that the double bond between C2 and C3 in ring C and the OH groups on C3' and C4' in ring B are critical for the biological activities. 8. This study demonstrates that the inhibitory effects of Lu and Qu, and the stimulatory effects of EGF, on tumour cell proliferation, cellular protein phosphorylation, and MMP secretion may be mediated at least partly through EGFR. This study supports the idea that Lu and Qu may have potential as anti-cancer and anti-metastasis agents.

Autoradiography↗

PubMed1999

Molecular cloning and characterization of a hemolymph clottable protein from tiger shrimp (Penaeus monodon).

To investigate the coagulation system in crustacean decapoda, a homodimeric glycoprotein of 380 kDa was purified from the hemolymph of tiger shrimp (Penaeus monodon) by sequential DEAE anion exchange chromatography. The purified protein was coagulated by the shrimp hemocyte transglutaminase in the presence of Ca2+. The clottable protein contains 44% alpha helices and 26% beta sheets as determined by circular dichroism spectra. Its conformation is stable in buffer of pH 4-9. To solve its primary structure, partial sequences of the purified polypeptides from cyanogen bromide cleavage and endopeptidase digestion were also determined. A shrimp cDNA expression library was constructed. By combination with antibody screening, reverse transcriptase PCR using degenerate primers from determined amino acid sequences and cDNA library screening with digoxigenin-labeled DNA probes, the entire cDNA of 6124 bp was obtained. This cDNA encodes a protein of 1670 amino acids, including a 14-amino acid signal peptide. With four potential N-glycosylation sites, the clottable protein was found to contain 3.8% high-mannose glycan; and Man8GlcNAc and Man9GlcNAc were released upon endo-beta-N-acetylglucosaminidase hydrolysis. Upon conducting a protein sequence database survey, the shrimp clottable protein shows 36% identities to the crayfish clotting protein and lower similarities to members of insect vitellogenins, apolipoprotein B and mammalian von Willebrand factor. Notably, a region rich in Gln residues, a polyGln motif and five Ser-Lys-Thr-Ser repeats are present in the shrimp protein, suggesting this protein might be a transglutaminase substrate. Northern blot analysis revealed that the clottable protein is expressed in most of the shrimp tissues but not in the mature hemocytes.

Amino Acid Sequence↗

PubMed1999

Expression of green fluorescent protein in oligodendrocytes in a time- and level-controllable fashion with a tetracycline-regulated system.

Developments in transgenic technology have greatly enhanced our ability to understand the functions of various genes in animal models and relevant human diseases. The tetracycline (tet)-regulated transactivation system for inducing gene expression allowed us to control the expression of exogenous genes in a temporal and quantitative way. The ability to manipulate a cell-specific promoter enabled us to express one particular protein in a single type of cell. The combination of a tetracycline system and a tissue-specific promoter has led us to the development of an innovative gene expression system, which is able to express genes in a cell type-specific and time- and level-controllable fashion. An oligodendrocyte-specific myelin basic protein (MBP) gene promoter controls the reversed tet-inducible transactivator. The green fluorescent protein (GFP) gene was placed under the control of the human cytomegalovirus (CMV) basic promoter in tandem with seven tet-responsive elements (TRE), binding sites for the activated transactivator. Upon the addition of doxycycline (DOX, a tetracycline derivative), tet transactivators became activated and bound to one or more TRE, leading to the activation of the CMV promoter and the expression of GFP in oligodendrocytes. We have successfully expressed GFP and luciferase at high levels in oligodendrocytes in a time- and dose-dependent fashion. In the absence of DOX, there was almost no GFP expression in oligodendroglial cultures. Graded levels of GFP expression were observed after induction with DOX (0.5 to 12.5 microg/ml). Our data indicate that this inducible gene expression system is useful for the study of gene function in vivo and for the development of transgenic animal models relevant to human diseases such as multiple sclerosis.

Animals↗

PubMed1999

Intubation of newborn during delivery with intact umbilical cord--a case report.

A 24-year-old gravida 2, para 1 woman at 38th week gestation was scheduled for elective Cesarean section (C/S) because of a previous C/S and prenatal diagnosis of congenital diaphragmatic hernia. We decided to intubate the newborn during delivery before the umbilical cord was cut. After delivery of the fetal head and part of the shoulders, the mouth of the fetus was cleared and the trachea was intubated orally with a 2.5 mm internal diameter (I.D.) endotracheal tube under sterile conditions while the uteroplacental circulation was still intact. The patient had to be repeatedly resuscitated due to bradycardia in intensive care unit. No surgical correction of the hernia was attempted because of the poor condition of the baby, which died 3.5 hours after birth. Although our case ended up in mortality despite successful perinatal intubation, we recommend that in case where airway or ventilatory problems are anticipated, tracheal intubation is done during delivery before the umbilical cord is clamped. When the fetus is sharing the maternal circulation, it will allow physicians to have more time and safety to perform corrective measures.

Adult↗

PubMed1999

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↗

PubMed1999

Evaluation of serum CA27.29, CA15-3 and CEA in patients with breast cancer.

The Truquant BR radioimmunoassay (RIA) using monoclonal antibody BR 27.29 to recognize a peptide sequence on the MUC-1 gene product for quantification of the CA 27.29 antigen in serum was used in this report to evaluate in 145 patients with breast cancer and compared the other conventional serum markers such as CA15-3 and CEA. The upper limit of normal (25 u/ml) was determined from CA27.29 values 12.4 +/- 4.1 u/ml (mean +/- 3 S.D.) for 112 female subjects apparently free of disease. The CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. Thirty-seven cases of 145 patients studied had elevated CA 27.29 levels (sensitivity: 25.5%), 35 of 145 had positive CA15-3 levels (sensitivity 24.1%) and 27 of 145 patients had positive CEA levels (sensitivity: 18.6%) (p < 0.05). One hundred and ten cases of the breast cancer patients (75.8%) did not have metastatic disease. In this group CA 27.29 sensitivity was 6.4%, while CA15-3 sensitivity was 5.5% and CEA sensitivity was 4.5% (p > 0.05). Mean values were 10.2 +/- 9.2 u/ml for CA 27.29, 14.1 +/- 5.6 u/ml for CA 15-3 and 1.7 +/- 1.5 ng/ml for CEA. Thirty-five patients (24.2%) had metastatic disease. In this group CA 27.29 sensitivity was 85.7%, CA15-3 sensitivity was 82.8% and CEA sensitivity was 62.8% (p < 0.05). Mean values for CA27.29 was 152.6 +/- 131.6 u/ml, CA15-3 was 123.1 +/- 107.6 u/ml and 21.8 +/- 36.9 ng/ml of CEA. With regard to the correlation of three tumor markers with clinical stages, patients had significantly higher levels of CA27.29 than CEA, but they were similar to CA 15-3 in metastatic breast cancer. These results suggest CA27.29 to be more sensitive and specific than CEA, but that it is similar to CA15-3 for metastatic breast cancer detection and monitoring.

Adult↗

PubMed1999

Direct comparison of liposomal doxorubicin with or without polyethylene glycol coating in C-26 tumor-bearing mice: is surface coating with polyethylene glycol beneficial?

Sterically stabilized liposome is characterized by a surface coating of polyethylene glycol (PEG) or other polymers that can reduce opsonization of the liposome by plasma proteins. It has a higher plasma area under the concentration-time curve (AUC), which is believed to correlate with better therapeutic efficacy. However, the presence of large molecules on the liposomal surface may reduce the interactions of liposomes with cells and hinder entry of liposomes into the tumor tissue. Using a stable liposomal system composed of distearoyl phosphatidylcholine/cholesterol, we examined the effect of PEG (Mr 2000) on the pharmacokinetics and on the efficacy of liposomal doxorubicin with C-26 syngeneic tumor model in BALB/c mice. The plasma AUC of liposomal doxorubicin with 6 mol-% PEG-modified distearoyl phosphatidylethanolamine (PEG-DSPE) was approximately twice that of liposomal doxorubicin without PEG at various dosages, regardless of whether the mice were tumor-bearing. Paradoxically, the group of mice treated with liposomal doxorubicin without PEG had higher tumor doxorubicin concentrations. The 72-h tumor AUC was 1.44 times that of liposomal doxorubicin with 6% PEG-DSPE. The tumor-accumulation efficiency (AUC(Tumor)/AUC(Plasma)) of liposomal doxorubicin without PEG was 0.87, and this was more than twice that of the liposomal doxorubicin with 6% PEG-DSPE (0.31). At a dose of 10 mg/kg, although both liposomal groups were better than the free drug group in terms of clinically relevant parameters, including toxicity, tumor shrinkage, and survival, there was no difference between the two liposomal drug groups. In this stable liposome system, surface coating with PEG offered no benefit for liposomal doxorubicin in the C-26 tumor model. To enhance the therapeutic index of liposomal doxorubicin, simply increasing plasma AUC by surface coating with PEG may not be satisfactory.

Animals↗

PubMed1999

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↗

PubMed1998

Differential effects of dexamethasone and RU 486, an antigestagen and antiglucocorticoid, on progesterone and relaxin secretion in hysterectomized pigs with aging corpora lutea.

Pregnancy lasts about 114 days in pigs. Porcine corpora lutea produce not only progesterone but also relaxin (RLX), a peptide hormone that plays a critical role in suppressing uterine motility during pregnancy and in remodelling connective tissues in preparation for imminent parturition. Progesterone concentrations in peripheral blood remain elevated (approximately equal to 25 ng ml-1) for the major part of pregnancy and decrease just before parturition. The decrease in progesterone coincides with the peak prepartum RLX release. Glucocorticoid or antiglucocorticosteroid steroid, RU 486, administration during late pregnancy can induce parturition in the pig. Peak release of RLX and a coincident decrease of progesterone in the circulating blood can also occur in the complete absence of fetuses and uterus in the pig. The effects of glucocorticoid or antiglucocorticoidsteroid administration to such hysterectomized pigs on the secretion of RLX and progesterone were examined in this experiment. Unmated Yorkshire gilts were hysterectomized on days 6-8 (estrus = day 0) and given dexamethasone (total of 30 mg day-1; 2 times i.m. at 0800 and 1600 h) from days 110-118; control animals received vehicle injection during this period. RU 486 (4 mg kg1 body weight) was orally administered once daily (days 111-115) at 0800 h; placebo-treated controls were given the same amount of feed without the drug at this time. RLX concentrations in blood were markedly suppressed (P < 0.01) during dexamethasone treatment (3 +/- 0.9 ng ml-1; mean +/- S.E.) whereas a peak release of RLX (17 +/- 2.8 ng ml-1) occurred in the control group on day 113. In contrast, progesterone concentrations (14 +/- 2.5 ng ml-1) were unaffected by dexamethasone treatment compared with the controls (15 +/- 2.0 ng ml-1; P > 0.82). Upon withdrawal of dexamethasone on day 118, RLX plasma concentrations began to increase and peaked at 14 +/- 2.1 ng ml-1 (P < 0.01) on day 120. In contrast, the antiglucocorticosteroid given to hysterectomized pigs bearing aging corpora lutea caused a marked elevation in circulating levels of progesterone and delayed RLX release until after the end of drug treatment on day 115. Average weights of corpora lutea collected at day 12 were similar between treated and control groups (427 +/- 7 vs. 433 +/- 6 mg; P > 0.68). Results indicate that a synthetic glucocorticoid, dexamethasone, suppresses RLX secretion without causing luteolysis and such suppression is reversible; progesterone secretion remained unaffected. In contrast, the antiglucocorticoid, RU 486, raised progesterone plasma concentration and delayed RLX peak release but did not suppress it during treatment. This experiment provides further evidence that relaxin and progesterone secretion from aging corpora lutea of pigs are regulated through separate mechanisms, and adrenal glucocorticoids may be involved in such a regulation process.

Animals↗