Cellular and molecular mechanisms of low dose prolactin potentiation of testicular development in cockerels.

The aim of this study was to determine the cellular and molecular mechanisms of prolactin (PRL) in testicular development of prepubertal cockerels. In an in vivo animal experiment, active immunization against PRL severely depressed prepubertal testicular development by significantly reducing testicular weights at both 122 and 164 d of age. The number of elongated spermatids in the seminiferous tubules was also significantly decreased by immunization with 199-residue chicken PRL (cPRL) at age 122 d. Inhibition of testicular development by cPRL immunization was associated with decreases in LH receptor (LHR), FSH receptor (FSHR), Stat5b, P450scc, steroidogenic acute regulatory (StAR) protein, and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) mRNA expression levels in testicular tissue. In in vitro experiments, testosterone production by cultured Leydig cells isolated from prepubertal cockerel testes was dose-dependently enhanced by treatment with bioactive recombinant PRL, but a lesser response was seen with high concentrations of PRL. The distinct changes in testosterone production in response to high and low concentrations of added PRL were paralleled by similar patterns of change in the mRNA levels of Stat5b, LHR, P450scc, StAR, 3ß-HSD, and CYP17A1 in cultured Leydig cells, as well as protein amounts of phosphorylated Jak2 and Stat5a/b. In conclusion, low to medium doses of PRL potentiate testis development in prepubertal cockerels by enhancing testosterone secretion from Leydig cells via activation of PRLR/Stat5b signal transduction, which upregulates mRNA expression of LHR and testosterone synthesizing enzymes. However, this positive regulation was weaker in response to a high dose of PRL, which reduced PRLR/Stat5b signal transduction and the expression of genes involved in LH signaling and testosterone synthesis.

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-kappaB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner.

Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-XL downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-kappaB inactivation by preventing NF-kappaB nuclear translocation and inducing IkappaBalpha cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.

Versatile user interface using UMLS Metathesaurus.

One of the obstacles for a successful search in the biomedical field is that different vocabularies are used by different databases but more than one database is usually needed to respond adequately to a healthcare professional's query. A typical searcher usually is unfamiliar with these vocabularies and the sophisticated measures to narrow or broaden a search. As a result, a failed search is often due to using "inappropriate" search terms. We have developed a highly interactive and versatile user interface, SHINE Refined Search (SHINE RS). It uses medical concepts from the UMLS Metathesaurus as the building block to help searchers find "appropriate" search terms for their queries. The results of our preliminary usability assessment are promising and demonstrate the potential to improve retrieval results.

[Modulation of the secretion of active renin in human decidual cells by progesterone].

Uterine decidua is a major source of renin, both active and inactive. Active renin cleaves angiotensinogen to produce angiotensin I and exerts its effect on the expression of angiotensin II in the local tissue. Our experiments showed that (1) in the decidua of early pregnancy the contents of active renin increased gradually with advancing pregnancy, and at 8th week of gestation the level of active renin reached to a maximum (63.37 +/- 12.84) AI ng/gww.h(-1); (2) active renin accounted for about 1/4 of the total renin; and (3) the synthesis and secretion of active renin were regulated by progesterone in incubated decidual cells. These data indicate that a high level of active renin in decidual tissue at early pregnancy plays an important role in the uterine renin-angiotensin system during pregnancy.

Neonatal gastric aspirates as a predictor of perinatal hepatitis B virus infections.

OBJECTIVE: To elucidate possible routes and predictors of perinatal transmission of hepatitis B virus (HBV). METHOD: This was a prospective follow-up study. One hundred and forty-seven out of 1762 pregnant women who were screened in the antenatal clinic of a university teaching hospital were HBsAg carriers. Enzyme immunoassay was used for determination of hepatitis B markers. Occurrence of HBsAg in newborns' gastric aspirates, newborns' and infants' blood, and maternal milk samples were determined. Their relationship with delivery routes and duration of the first stage of labor were analyzed by chi square test. RESULTS: The presence of HBsAg in newborns' gastric aspirates was strongly associated with the acquisition of HBsAg by the babies. There was no correlation between the rate of infant antigenemia and the duration of the first stage of labor, nor did cesarean section decrease the rate of vertical transmission of HBV. CONCLUSIONS: This is the first report to provide direct evidence for the major role of the oral route in vertical transmission of HBV during delivery. In addition to maternal serum HBeAg, HBsAg status in newborn's gastric aspirates is another important determinant for vertical transmission of HBV.

[Tissue concentration and secretion of renin in human placental villi during early pregnancy].

In this study, tissue concentrations of renin and angiotensins in human placental villi during early pregnancy and contents of renin and angiotensin I (A I) secreted by cultured chorion were measured by radioimmunal assay (RIA). The results are as follows. During early pregnancy, the human chorion contains renin and A II. The activity of renin is much higher at 6th week of gestation, but as gestation proceeds, it decreases gradually, while A II shows somewhat increased change. The activity of renin secreted by cultured chorion can also be measured. A I in human placental villi can not be detected by RIA in chorion leaves or their culturing fluid. These results indicate that renin-angiotensin system may exist independently in human placental villi during early pregnancy.

Enhanced ribosomal association of p27(Kip1) mRNA is a mechanism contributing to accumulation during growth arrest.

p27(Kip1) regulates the decision to enter into S-phase or withdraw from the cell cycle by establishing an inhibitory threshold above which G1 cyclin-dependent kinases accumulate before activation. We have used the HL-60 cell line to study regulation of p27 as cells withdraw from the cell cycle following treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA). We found that the amount of p27 is maximal in G0 cells, lower in G1 cells, and undetectable in S-phase cells. In contrast to the protein, the amount of p27 mRNA was the same in these populations, suggesting that accumulation of p27 during the cell cycle and as cells withdraw from the cell cycle is controlled by post-transcriptional mechanisms. In S-phase cells, the degradation of p27 appears to predominate as a regulatory mechanism. In G0 cells, there was an increase in the synthesis rate of p27. Our data demonstrate that, in G0 cells, accumulation of p27 is due to an increase in the amount of p27 mRNA in polyribosomes.

Formation of p27-CDK complexes during the human mitotic cell cycle.

In eukaryotic cells, the coordinated activation of different cyclin-dependent kinases regulates entry into S-phase. In vitro and in nonproliferating cells, p27 associates with and inhibits cyclin/cycin-dependent kinase (CDK) holoenzymes containing either CDK4, CDK6, or CDK2. Although many different types of proliferating cells contain p27 protein, neither the interactions of p27 with cyclin/CDK complexes nor the consequences of this interaction during the mitotic cycle have been fully explored. We report that, in MANCA cells, the amount of p27 is constant during the cell cycle. In addition, p27 associates with three different CDKs: CDK2, CDK4, and CDK6. Furthermore, the amount of p27 is significantly lower than the amount of cyclin D3 in these cells. The amount of CDK4 and CDK6 associated with p27 does not change in a cell cycle-dependent fashion; in contrast, the amount of CDK2 associated with p27 is lowest in early G1 cells and increases to a maximum in mid-G1 phase, reaching a steady-state level in late G1-phase cells. After mid-G1 phase, the amount of each p27/CDK complex remains constant through the remainder of the cell cycle. p27-immunoprecipitates contain an Rb-kinase activity. The substrate specificity, the expression pattern of this kinase, and the ability to deplete 50% of this kinase activity with a CDK6-specific antibody suggest that the CDK6 protein mediates, in part, the p27-associated Rb-kinase activity. In contrast, p27 complexes containing CDK2 are incapable of phosphorylating histone H1. These data are consistent with a model wherein cyclin D/CDK complexes sequester the CDK2-dependent kinase inhibitory activity of p27.

Establishment of the sulfated 3,3'-diiodothyronine radioimmunoassay and its application in pregnant women.

Sulfation of iodothyronines is a major alternate pathway of thyroid hormone metabolism during fetal development. Sulfated 3,3'-diiodothyronine (T2S) is a low end metabolite of this pathway. Its clinical implications in the prenatal evaluation of fetal thyroid disorders are now being intensively investigated. A highly sensitive and reproducible radioimmunoassay (RIA) for T2S has been established in our laboratory. The detection threshold of the RIA approximated 5 pg T2S. The dose-response curve of T2S was essentially linear between 5-200 pg. An essentially parallel correlation of the dose-response curves for inhibition of binding of radiolabeled T2S and T2S antiserum was found between serial dilutions of serum extracts and the standards. The average intra- and inter-assay coefficients of variation were 7% and 15%, respectively. By applying the T2S RIA, we found that serum titers of T2S in pregnant women increased proportionately to the gestational age (first trimester vs. second trimester vs. third trimester: 30.1 +/- 1.4 vs. 41.6 +/- 1.9 vs. 98.0 +/- 3.9 ng/dL; p < 0.001 each). A high concentration of T2S was detected in cord and maternal serum at birth as compared to the results for non-pregnant women (165.1 +/- 10.3 vs. 113.7 +/- 5.6 vs. 7.5 +/- 0.9 ng/dL). The T2S levels decreased remarkably in maternal circulation 10 days after partuition. Four pregnant women who had two blood samplings four or more weeks apart during the third trimester showed invariable increases of serum T2S titers at later sampling times. Additionally, in the case of a pregnant woman who received two doses of T4 injections (200 micrograms/wk) intraamniotically for a previous Cretin birth, the maternal serum levels of T2S increased promptly from 47 ng/dL [corrected] to 96 ng/dL. Our findings imply that the established T2S RIA is clinically applicable, provide further evidence that the coincident increase of serum T2S titers in pregnant women may reflect ontogenesis of fetal thyroid hormone maturation, and provide a clue to the fetal thyroid status in the prenatal stage. However, more knowledge is still needed regarding the transfer and transformation of sulfated iodothyronine(s) from the fetal compartment to maternal circulation.

[Clinical application and technical problems of colonic interposition for esophageal substitution].

From Jan. 1980 to Jan. 1991, A total 41 patients, including 22 patients with corrosive stricture after esophageal chemical burns, 10 patients with cancer of the laryngopharynx, 7 patients with esophageal cancer and 1 case of cardiac carcinoma, underwent of colonic interposition for esophageal substitution. This accounted 0.7% of all of the esophageal reconstruction during the same period. There were 23 cases of retrosternal colonic bypass and 18 cases of trans-hiatal inversion-stripping esophagectomy without thoracotomy. The main postoperative complications were anastomotic leakage at the cervical region and incision infection, but no mortality. The indications, choice of the colonic segment and the technical problems of this operation were discussed.

Elective cesarean section for macrosomia?

BACKGROUND: Fetal macrosomia is associated with increased risk of dystocia and birth trauma. Elective Cesarean section has been recommended for macrosomic fetus to prevent the associated complications. However, the cost/benefit ratio of such practice should be known before it can be considered appropriate. METHODS: The record of 6230 women delivered consecutively at Tri-Service General Hospital were reviewed retrospectively. The occurrence rates of dystocia and birth trauma were compared between normal birthweight group (2500-3999 gm) and macrosomic group (> or = 4000 gm). The complication rates were calculated specifically among those macrosomic infants delivered vaginally. RESULTS: Of the 6230 singleton pregnancies, 207 had an infant weighing at least 4000 gm. One hundred and three macrosomic infants were delivered by Cesarean section. The indication for Cesarean section was dystocia in 25, estimated fetal macrosomia in 30 and other, 48. If only those pregnancies with macrosomic infant allowing an adequate trial of labor were considered, the frequency of Cesarean section for dystocia was 19.1% in the 4000-4999 gm group and 21.4% in the 4500 gm group, compared with 4.4% in the normal birthweight group. No birth trauma occurred in the macrosomic infants delivered by Cesarean section. Of those macrosomic infants delivered vaginally, the frequency of clavicle fracture was 11.8% in the 4000-4499 gm group and 18.2% in the > or = 4500 gm group, compared with 1.2% in the normal birthweight group. Two infants (18.2%) weighing greater than 4500 gm sustained brachial plexus injury. CONCLUSIONS: Elective Cesarean section on macrosomic infants to prevent dystocia is not recommended because most of them can be delivered vaginally. For the very macrosomic infants (> or = 4500 gm), elective Cesarean section is suggested to prevent birth trauma.

Reproductive performance following ectopic pregnancy.

The reproductive performance subsequent to operative removal of ectopic pregnancy was examined in 132 women. They represent 44.6% of 296 women admitted for ectopic pregnancy between 1981 and 1989. The follow-up period ranged from 6 months to 9 years, averaging 3.6 years. During the follow-up period, 69 (52.3%) pregnancies occurred. Among them, 60 (87%) were intrauterine and 9 (13% of the pregnant women) were repeated ectopic pregnancies. Full-term delivery was obtained in 73.9% of the pregnant patients. Forty of the 132 patients received conservative surgery and 92 patients received radical surgery for ectopic pregnancy. The operation method had no influence on subsequent fertility in women with an intact contralateral tube, who had significantly higher pregnancy (p less than 0.005) rate (3.8%) than women with an affected contralateral tube (39.5%, 47% and 41%, respectively). Compared with parous women (13.3%), the risk of repeated ectopic pregnancy was similar to nulliparous women (12.5%), but the nulliparous women had a slightly lower conception rate (40%) than parous women (54.8%). Unruptured ectopic pregnancies comprised 41.6% of our cases. There was no significant difference in fertility rate between ruptured and unruptured ectopic pregnancies in our study.

No decline in preterm birth rate over three decades.

Low socioeconomic status has been associated with risk of preterm delivery. During the past 30 years, Taiwan has had tremendous economic growth and people have attained higher levels of education and living. It is thus not unreasonable to presume that the rate of preterm delivery would decline in response to these changes. The birth registry of Tri-Service General Hospital from 1957 to 1987 was reviewed. The rate of preterm delivery remained stable over the past 30 years, unaffected by these country-wide social changes.

Pregnancy in patients with systemic lupus erythematosus.

Ten pregnancies in patients with systemic lupus erythematosus were reviewed. Preterm delivery occurred in 4 cases (40%), fetal growth retardation in 2 (20%) and intrauterine death in 2 (20%). Preeclampsia developed in one case, which was the only found maternal complication. The most important factor associated with poor outcome was lack of antenatal care. Most of the SLE-complicated pregnancies can anticipate a favorable outcome if, and only if, there is a well-planned management with close cooperation among the patient, obstetrician, rheumatologist and neonatologist.

Comparative study of Filshie clip and Pomeroy method for postpartum sterilization.

A prospective randomized comparison of the peri-operative complications and long-term sequelae between the Filshie clip and Pomeroy methods was undertaken in 200 postpartum women at Tri-Service General Hospital, Taipei, Taiwan. The peri-operative complications in either group were mild and infrequent. One pregnancy in the Pomeroy group was reported after follow-up for 24 months. No significant difference between the two groups was found in respect to long-term sequelae.

A facile synthesis of [14C] epicholesterol.

A facile procedure is described for the preparation of [14C]epicholesterol from [14C]cholesterol. Cholesterol is first converted to cholesteryl mesylate, which is treated with cesium acetate and 18-crown-6 in refluxing toluene to give epicholesteryl acetate. The latter is hydrolyzed, without isolation, with potassium hydroxide in tetrahydrofuran-methanol to give epicholesterol, which is obtained in pure form by preparative thin-layer chromatography.

[Multicentric carcinoma of the esophagus and double primary malignant neoplasm of the upper alimentary tract--report on 44 patients].

During the past fifteen years, 44 patients with multicentric carcinoma of the esophagus or double primary malignant neoplasm of the upper alimentary tract, collected from 5316 patients with cancer of esophagus or gastric cardia in the same period, were treated in our hospital. The incidence was 0.83%. All were proven by pathology. Exploratory thoracotomy was done in 32 patients and 26 lesions were resected with a resection rate of 81.3%. All patients with cancer resected survived over 1 year, 6 out of 9 survived over 3 years and 2 out of 3, over 5 years. In the 18 patients who received chemotherapy alone, 12 were followed and all died within 1 year. It is shown that multicentric carcinoma of the esophagus or double malignant neoplasm of the upper alimentary tract should be given energetic treatment. Finally, the incidence, diagnosis criteria, diagnosis method, etiology and management are discussed with a review of literature.