Biomedical subjects

F F Liu

Publications and source records attributed to F F Liu.

At least 55 records · Page 3Linked to original sources

PubMed1996

The stress-activated protein kinase pathway mediates cell death following injury induced by cis-platinum, UV irradiation or heat.

BACKGROUND: Stimuli that stress cells, including inflammatory cytokines, ultra-violet irradiation, DNA-damaging chemotherapeutic drugs and heat shock, stimulate a recently identified cytoplasmic signaling system that is structurally related to the mitogen-activated protein kinase pathway. This pathway consists of a cascade of protein kinases including stress-activated protein kinase (SAPK), also termed Jun N-terminal kinase (JNK), and two kinases that activate it, MEKK and SEK/MKK4. Despite rapid progress in delineating the components of this pathway, the cellular consequence of its activation remains to be defined. RESULTS: We have screened cells for defects in SAPK signaling and identified a cell line, previously characterized for its thermotolerance properties, as being more refractive to SAPK activation induced by heat stress than its thermosensitive parental line. Stable expression of dominant inhibiting SEK mutants in thermosensitive parental cells specifically and effectively blocked SAPK activation after heat shock. These lines also became markedly resistant to the cytocidal effects of thermal stress, confirming the phenotype of the thermotolerant line. These cell lines defective in SAPK activation were also resistant to the lethal effects of the DNA-damaging drug cis-platinum. CONCLUSIONS: Experimentally induced stable blockade of SAPK activation in cells with normal thermosensitivity is sufficient to confer resistance to cell death induced by diverse stimuli including heat and the chemotherapeutic agent cis-platinum. These results suggest that activation of the SAPK pathway by diverse cell stressors plays a critical part in mediating the toxicity of these treatments and inducing cell death. SAPK activation in this context could broadly influence cellular response to stress, modulate apoptosis during development or determine the clinical response of tumor cells to cytotoxic therapies.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1996

The effect of heat on Na+/H+ antiport function and survival in mammalian cells.

PURPOSE: Because intracellular pH (pHi) is a determinate of thermosensitivity, it is important to understand the relationship between heat cytotoxicity and the mechanisms responsible for pHi regulation, such as the Na+/H+ antiport. The objective of this study is to elucidate the relationship between heat damage and Na+/H+ antiport activity. METHODS AND MATERIALS: Various cell lines, EMT6, RIF-1, and its thermoresistant variant TR-4, and CCL39, and its variant that lacks the Na+/H+ antiport (PS120), were all heated using a water bath. Parallel assessments of antiport function and pHi were made using the fluorescent dye 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). RESULTS: Exposure of EMT6 cells to 43-46 degrees C for 30-60 min caused progressive decline in antiport activity, in parallel with cytotoxicity. When the same degree of cytotoxicity was induced by ionizing radiation, no alteration in Na+/H+ antiport function was observed. Despite a 10-fold lower survival in RIF-1 compared to TR-4 cells after heating, there was no difference in the thermosensitivity of their antiports. Antiport activity in the TR-4 cells, however, was higher than that of RIF-1 cells both before and during heating. Intracellular pH for TR-4 cells decreased minimally during heating, in contrast to a decline of 1 pH unit in RIF-1 cells despite similar relative levels of antiport activity, suggesting that in this pair of cell lines, antiport activity does not play a major pHi regulatory role. PS120 and CCL39 cells and similar survival levels when heated at pHe 7.2 in the presence of NaHCO3, which allows function of the other major regulator of pHi, the Na+ -dependent HCO3-/Cl- exchanger. This occurred despite a drop in pHi in the PS120 cells during heating. A reduced survival was observed, however, in PS120 cells after 43 degrees C for 30-60 min at either pHe 6.5 or pHe 7.2 in the absence of NaHCO3. Intracellular pH was consistently greater for PS120 than CCL39 cells. CONCLUSION: We demonstrated that damage to the Na+/H+ antiport likely reflects early heat-induced change in membrane function, but is not a primary target for heat cytotoxicity. Although there is an association between survival, antiport function, and pHi level under most treatment conditions, the precise role of the Na+/H+ antiport in mediating thermal cytotoxicity remains uncertain.

Animals↗

PubMed1996

Prenatal diagnosis of partial monosomy 3p and partial trisomy 2p in a fetus associated with shortening of the long bones and a single umbilical artery.

The prenatal and postnatal findings of a fetus with partial deletion of 3p25 -> pter and duplication of 2p25.3 -> pter are described. The proband postnatally displayed mental and growth retardation, psychomotor delay, microcephaly, ptosis, micrognathia, a narrow palate, and cryptorchidism. All of these anomalies were consistent with those described in 3p- and partial trisomy 2p syndromes, and also frequently seen in patients with other chromosomal disorders. However, the prenatal sonograms revealed unusual shortening of the long bones, a single umbilical artery, and normal development of the skull. Our case suggests that skeletal growth retardation of the long bones may occur earlier than that of the skull in fetuses associated with chromosomal aberrations such as del(3p)/dup(2p). Shortening of the long bones and a single umbilical artery together with other abnormalities detected by prenatal ultrasound thus warrant a fetal cytogenetic study.

Abnormalities, Multiple↗

PubMed1996

Ultrasound-guided fluid aspiration and prenatal diagnosis of duplicated hydrometrocolpos with uterus didelphys and septate vagina.

We report on a case of duplicated hydrometrocolpos with uterus didelphys, a septate vagina, lower vaginal atresia, a persistent urogenital sinus, left ear agenesis, a single umbilical artery, and an imperforate anus, but without the associated features of McKusick-Kaufman syndrome such as polydactyly and congenital heart defects. Ultrasound-guided fluid aspiration of the fetal intrapelvic cystic mass helped to decompress the distended genital organs, decrease the severity of the urinary tract obstruction, delineate the ultrasonographic image of duplicated hydrometrocolpos to differentiate it from other intrapelvic cystic masses, and obtain fluid for cytological analysis.

Abnormalities, Multiple↗

PubMed1996

Prenatal diagnosis of partial monosomy 13q associated with occipital encephalocoele in a fetus.

The pre- and postnatal findings of a fetus with a de novo del(13)(pter-->q21:) and an occipital encephalocoele are described. Maternal serum alpha-fetoprotein (AFP) screening at 19 weeks' gestation demonstrated a high level of 2.5 multiples of the median (MOM) and ultrasonography at 27 weeks' gestation showed severe intrauterine growth retardation, cardiomegaly, an occipital encephalocoele, and a calvarial defect. Genetic amniocentesis revealed a karyotype of 46,XX,del(13)(pter-->q21:). The proband postnatally displayed additional abnormalities such as microphthalmia, hypertelorism, large low-set ears, and micrognathia. We discuss the association of central nervous system (CNS) malformations with 13q deletions and emphasize that pregnancies with neural tube defects warrant cytogenetic analysis, especially when additional fetal abnormalities and neonatal dysmorphism are observed.

Adult↗

PubMed1996

Prenatal diagnosis of supernumerary der(22)t(11;22) associated with the Dandy-Walker malformation in a fetus.

We present the first report of prenatally diagnosed Dandy-Walker malformation with the karyotype of partial trisomy 11 and 22 due to familial translocation t(11;22)(q23;q11) inherited in three generations. We demonstrate that the Dandy-Walker malformation can be an associated congenital malformation of supernumerary der(22)t(11;22) syndrome and emphasize the importance of chromosomal analysis and genetic counselling in the obstetric management of prenatally diagnosed Dandy-Walker malformation.

Adult↗

PubMed1996

Male breast cancer: an 11 year review of 66 patients.

A review was conducted of 66 men with carcinoma of the breast seen at this institution between 1981 and 1992. The results of the study suggest that there are many similarities between breast cancer in men and women. The most common clinical presentation was a lump in the breast. The majority of tumors were T1 or T2, and infiltrating ductal carcinoma was the predominant histological type. Axillary nodal status and histological grade were predictive of survival. The pattern of recurrence and survival rates were similar to those seen in women. Some differences, however, were evident. Tumors were centrally located in the majority of patients and there was a high frequency of nipple involvement. The hormone receptor positivity rate was high and the median age at presentation was older. In comparison to a previous report of the same disease from this institution 10 years ago, fewer patients underwent radical surgical procedures and more patients received adjuvant systemic therapy. These approaches are justified since there are many biological similarities between breast cancer in men and women.

Adult↗

PubMed1996

The relationship between thermosensitivity and intracellular pH in cells deficient in Na+/H+ antiport function.

BACKGROUND AND PURPOSE: We have demonstrated previously the relationship between intracellular pH (pHi) level and heat survival in mammalian cells. To explore this in further detail, we studied thermosensitivity in CCL 39 and their variant PS120 cells, which lack Na+/H+ antiport function. MATERIALS AND METHODS: CCL39 and PS120 cells were heated with or without amiloride, or 5-(N-ethyl(-N-isopropyl) amiloride (EIPA), inhibitors of Na+/H+ antiport function. Antiport activity and pHi measurements were made using the fluorescent dye 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF). A clonogenic assay was used to assess survival after heating. RESULTS: Enhanced cytotoxicity was observed when CCL39 cells were heated with either EIPA (15 microM) or amiloride (2.5 mM) at pHe7.3 in the presence of NaHCO3. Under the same conditions, thermal enhancement of PS120 cells was observed only with amiloride at 2.5 mM. When the cells were heated at pHe 6.5 in bicarbonate-free medium, both EIPA and amiloride enhanced thermal cytotoxicity in CCL39 cells, but only the higher dose of amiloride sensitized the variant PS120 cells. Surviving fraction was related to pHi, but the data fell into two clusters, depending on whether or not both Na+/H+ antiport and the Na(+)-dependent HCO3-/Cl- exchangers were functioning. CONCLUSIONS: We confirm that Na+/H+ antiport function can mediate thermosensitivity, and corroborate a linear correlation between pHi level and log survival after heating, but suggest that this relationship is complicated by other factors such as membrane exchanger function, and extracellular pH levels during heating.

Amiloride↗

PubMed1996

Prenatal diagnosis and perinatal aspects of abdominal wall defects.

We retrospectively reviewed 27 cases of omphalocele and 15 cases of gastroschisis occurring among 62, 572 deliveries between 1987 and 1994. All cases had undergone prenatal sonographic examinations at a mean gestational age of 28 weeks. In cases of omphalocele, 59.3% (16/27) of fetuses were associated with multiple malformations and 16% (4/25) had chromosomal abnormalities. Among the 4 cases with an abnormal karyotype, three cases were associated with extracorporeal livers and two cases were associated with umbilical cord cysts. Prenatal ultrasound examinations during the second and third trimesters were able to detect 66.7% (18/27) of the cases of omphalocele and 66.7% (10/15) of the cases of gastroschisis. Failure in correctly diagnosing abdominal wall defects by prenatal ultrasound occurred mostly in cases associated with small defects, ruptured omphalocele, multiple fetal anomalies, intrauterine fetal death, twin pregnancies, or cases referred in late gestation. A comparison of perinatal data between omphalocele and gastroschisis reveals fetuses with omphalocele carry higher risks of associated malformations, chromosomal abnormalities, prematurity, and neonatal death. Although fetuses with gastroschisis have higher incidences of oligohydramnios and small for gestational age, the fetal prognosis after pediatric surgery is good.

Abdominal Muscles↗

PubMed1996

Prenatal detection of the separation of the great toe, toe syndactyly, and large bilateral choroid plexus cysts in a fetus with trisomy 18.

Prenatal sonographic presentation of toe deformities is associated with fetal aneuploidies. This report presents a second-trimester fetus with large bilateral choroid plexus cysts, clenched hands, separation of the great toe, toe syndactyly, abnormal double maternal serum biochemical screening results, and trisomy 18. We suggest a careful ultrasound screening of the fetal limbs and other organs once a choroid plexus cyst has been identified. If abnormal sonographic findings are present, or if the results of the maternal serum biochemical screening are abnormal, karyotyping should be recommended.

Abnormalities, Multiple↗

PubMed1996

Prenatal diagnosis of asphyxiating thoracic dysplasia (Jeune syndrome).

Asphyxiating thoracic dysplasia (ATD), or Jeune syndrome, is an uncommon autosomal recessive skeletal disorder characterized by a small thorax, varying degrees of rhizomelic brachymelia, polydactyly, pelvic abnormalities, and renal anomalies. We describe prenatal sonographic examinations in the third trimester of a fetus with abnormal small thorax, short limbs, polyhydramnios, and absence of fetal respiratory movements. At 36 weeks gestation, the fetal biparietal diameter was 93 mm, compatible with 37 weeks; the long-bone lengths measured < 5th percentile; the thoracic circumference (TC) measured 230 mm (< 5th percentile); the abdominal circumference (AC) measured 286 mm (25th percentile), and the TC/AC ratio was 0.80 (lower limit of normal). Our case shows that, although a discrepancy between gestational age and TC is prominent, TC/AC ratio may reach lower limit of normal in cases of fetal ATD, when fetal growth is compromised.

Adult↗

PubMed1996

Influence of heat on Na(+)-dependent HCO3-/Cl- exchanger function in a thermoresistant cell line.

During previous studies on the relationship between thermosensitivity and intracellular pH (pHi) regulation in mammalian cells, we observed that the thermoresistant TR-4 cells appeared to be resistant to manipulations of the Na+/H+ antiport, one of the two primary membrane regulators of pHi. We hypothesized that this might be due to up-regulation of the alternate pHi regulator, the Na(+)-dependent HCO3-/Cl- exchanger, in the TR-4 cells. We have now evaluated the effect of heat exposure on the function of the Na(+)-dependent HCO3-/Cl- exchanger in both the parent RIF-1 and the thermoresistant variant TR-4 cells. We also assessed thermosensitivity of the cell lines under conditions of either pHe 7.2 or 6.8, with NaHCO3, with or without the addition of DIDS, an inhibitor of HCO3-/Cl- exchanger function. After 2h of heating at 43 degrees C, relative exchanger function declined to around 50% for the TR-4 cells and 10% for the RIF-1 cells. DIDS (0.2 mM) enhanced thermal cytotoxicity in both cells lines, by around 1 log when the cells were heated at neutral conditions, and by around 1.5 log when the condition became acidic. Results from pHi measurements during heating reflected the clonogenic survival data in that lower pHi levels were associated with the conditions when DIDS was present. We conclude that in the TR-4 cells, the Na(+)-dependent HCO3-/Cl- exchanger appears to be a more important regulator of pHi than the Na+/H+ antiport.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

PubMed1996

A concealed penis mimicking penile agenesis in an infant with trisomy 13.

Penile agenesis results from failure in the development of the genital tubercle and is rarely associated with chromosomal abnormalities. We report on an echographic prenatal diagnosis of penile agenesis associated with trisomy 13. At birth, the contour of the penile shaft and the glans could not be seen. However, a careful palpation allowed us to determine that the penile shaft was concealed and normal in size, rather than penile agenesis being present. To our knowledge, a concealed penis associated with trisomy 13 has not previously been described.

Chromosomes, Human, Pair 13↗

PubMed1996

Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly.

Chromosome aberrations, mendelian mutations and exogenous agents can cause holoprosencephaly. Therefore, etiologic evaluation of holoprosencephaly is necessary for obstetricians and genetic counselors, once a prenatal diagnosis of holoprosencephaly has been made. We present four pregnancies in three women in which routine sonographic examinations led to the prenatal diagnosis of holoprosencephaly. Prenatal cytogenetic analysis and fluorescence in situ hybridization demonstrated a 46,XY,del(7)(pter-->q32:) and a 46,XY,der(2)t(2;3)(q37;p21)pat karyotype respectively in two fetuses with cyclopia, and a 46,XX,der(2)t(2;3)(q37;p21)pat and a 46,XX,der(7)t(3;7)(p23;q36) karyotype respectively in two fetuses with premaxillary agenesis. In conclusion, terminal deletion 7q and partial trisomy 3p in holoprosencephalic fetuses indicates that genes contributing to craniofacial development reside in these critical regions. Proper prognostic evaluation in further pregnancies requires expertise in cytogenetics and genetic counseling.

Adult↗

PubMed1996

Partial duplication of 3q and distal deletion of 11q in a stillbirth with an omphalocele containing the liver, short limbs, and intrauterine growth retardation.

We describe a female stillbirth with duplication of 3q21-->qter and deletion of 11q23-->qter resulting from an unbalanced segregation of a maternal t(3;11) reciprocal translocation. The proband had some of the clinical features consistent with those seen in patients with dup(3q) syndrome or distal del(11q) syndrome. Prenatal sonographic examination showed short limbs, intrauterine growth retardation, and an omphalocele containing the liver.

Chromosome Aberrations↗

PubMed1996

Cytogenetic evaluation of cystic hygroma associated with hydrops fetalis, oligohydramnios or intrauterine fetal death: the roles of amniocentesis, postmortem chorionic villus sampling and cystic hygroma paracentesis.

BACKGROUND: Pregnancies complicated by fetal cystic hygroma in the second and third trimesters are often associated with hydrops fetalis, oligohydramnios or intrauterine fetal death which may make genetic assessment more difficult. We investigated the roles of amniocentesis, postmortem chorionic villus sampling and cystic hygroma paracentesis in cytogenetic evaluation of cystic hygroma under such circumstances. METHODS: Thirty-five fetuses of cystic hygroma associated with hydrops fetalis, oligohydrammos, or intrauterine fetal death were studied. All fetuses were delivered at Mackay Memorial Hospital, Taipei, Taiwan between January, 1987 and July, 1995. Data collected included maternal age, prenatal sonograms, gestational age at diagnosis, fetal karyotypes and diagnostic procedures. RESULTS: Of 35 fetuses, all had hydrops fetalis, 19 had suffered IUFD at the time of diagnosis, and 10 had severe oligohydramnios. Cytogenetic studies were performed via amniocentesis, postmortem chorionic villus sampling, or cystic hygroma paracentesis. Successful karyotyping was achieved in 32 fetuses and the karyotype of 45,X was found in 24 fetuses. In cases with IUFD, successful karyotyping rates on cells from amniotic fluid, chorionic villi and cystic hygroma fluid were 88.9% (8 of 9), 69.2% (9 of 13) and 20% (1 of 5), respectively, whereas, in cases with living hydropic fetuses, successful karyotyping was achieved in 12 of 12 amniotic fluid and 5 of 5 cystic hygroma fluid samples. CONCLUSIONS: Amniocentesis is a better method for cytogenetic evaluation of fetal cystic hygroma associated with intrauterine fetal death than postmortem chorionic villus sampling and cystic hygroma paracentesis. However, in the case with a living hydropic fetus and oligohydramnios, cystic hygroma paracentesis appears to be a practical alternative for cytogenetic assessment.

Adult↗

PubMed1996

The relationship between intracellular pH and heat sensitivity in a thermoresistant cell line.

To explore further the relationship between intracellular pH (pHi) and thermosensitivity, we compared survival and pHi levels in RIF-1 cells and a thermoresistant variant, TR-4 cells, while heating under different conditions of acid or neutral extracellular pH (pHe). We also added 5-(N-ethyl-N-isopropyl) amiloride (EIPA), a potent inhibitor of one of the major membrane regulators of pHi, the Na+/H+ antiport, and/or removed NaHCO3 to inactivate the alternate membrane regulator of pHi, the HCO3-/Cl- exchanger. At pHe 7.3 with NaHCO3, EIPA (15 microM) did not enhance the cytotoxicity of heat in either cell line. At pHe 6.8 with NaHCO3, EIPA enhanced thermal cytotoxicity for RIF-1 cells only, but without NaHCO3, at pHe 6.8 or 6.5, EIPA treatment during heating resulted in a significant decrease in survival of TR-4 cells also. Measurements of pHi levels immediately after heating correlated with the survival data, demonstrating a linear relationship between pHi and log surviving fraction for both cell lines. This relationship, however, is different between the two cell lines in that the TR-4 cells are more resistant to reduction in pHi with heating, and for any given pHi level to demonstrate a higher correlation is different for the two cell lines, suggesting a difference in the relationship between pHi and log surviving fraction between the TR-4 and RIF-1 cells.

Amiloride↗

PubMed1996

Concurrent papillary and squamous carcinoma in a thyroglossal duct cyst: a case report.

Carcinomas of thyroglossal duct cysts are rare. Most are papillary carcinomas; only about 5% are squamous cell carcinomas. Only one case of mixed papillary and squamous cell carcinoma of a thyroglossal duct cyst has been reported so far. The authors present a second case, that of a 38-year-old man who was first seen with a midline neck lump. It was diagnosed clinically as a thyroglossal duct cyst and was locally excised. Pathological examination showed both a concurrent papillary carcinoma and a squamous cell carcinoma. Treatment consisted of a near-total thyroidectomy, ablative radioactive iodine and adjuvant external radiation therapy. The authors review the literature and explain the rationale behind their choice of treatment.

Adult↗