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Biomedical subjects

F J Lin

Publications and source records attributed to F J Lin.

At least 19 recordsLinked to original sources

Multiparametric analysis of cerebral substrates and nitric oxide delivery in cerebrospinal fluid in patients with intracerebral haemorrhage: correlation with hemodynamics and outcome.

BACKGROUND: There is no information regarding the possible role of cerebral substrates in the pathogenesis of neuronal injury in intracerebral haemorrhages (ICHs). Purposes of this prospective study were to clarify whether changes in substrates are the consequence of the initial brain damage in ICH and to elucidate the relationship among the biochemical mechanisms and clinical course of patients with ICH. METHOD: During a period of two years, patients (GCS < or =8) who had ICH secondary to an aneurysm (SAH), stroke (sICH), or trauma (tICH) and underwent ventriculostomy with ICP monitoring and/or underwent cranial surgery were randomly enrolled in this study. Extracellular concentrations of glutamate, aspartate, glycine, GABA, lactate, lactate/pyruvate ratio, and glucose in the CSF were measured by use of high-performance liquid chromatography (HPLC). The nitric oxide (NO) concentration in the CSF was analyzed by chemiluminescence. FINDINGS: There were 75 patients (38 women and 37 men) with ICH included in this study. Twenty-one patients had SAH, 28 sICH, and 26 tICH. In tICH patients, there was a 30-fold increase in glutamate and a 10-fold in aspartate over reference values. The levels of glutamate, aspirate, GABA, lactate, glucose, and NO differed significantly among the three groups (p<0.001). There were no significant differences in glycine and L/P ratio among the groups. The initial GCS, the mean CPP and outcome six months after the insult were all significantly correlated with the concentration of substrates (p<0.01), both within groups and among the total sample. The CSF levels of glutamate lactate, NO and glucose correlated significantly with outcome (p<0.005). CONCLUSIONS: This study confirms the correlation between the level of EAAs and the outcome of ICHs, suggesting that neurochemical monitoring of these substances may have a role in caring for patients.

Adult↗

Predominance of Th1 cytokine in peripheral blood and pathological tissues of patients with active untreated adult onset Still's disease.

OBJECTIVE: To determine the type 1 T helper (Th1)/type 2 T helper (Th2) balance in the peripheral blood (PB) and pathological tissues of patients with active untreated adult onset Still's disease (AOSD). METHODS: The percentages of interferon gamma (IFNgamma)- and interleukin (IL)4-producing Th cells in the PB of 20 patients with active untreated AOSD, 20 patients with active rheumatoid arthritis (RA), and 20 healthy controls were determined by intracellular staining and flow cytometry. Serum levels of IL18 and soluble IL2 receptor were measured by enzyme linked immunosorbent assay. Levels of IFNgamma and IL4 messenger (m) RNA expression were examined by real time quantitative polymerase chain reaction in biopsy specimens of evanescent rash and synovitis from 8 patients with AOSD. RESULTS: Significantly higher IFNgamma-producing Th cells and Th1/Th2 ratio in PB were found in patients with AOSD than in healthy controls. Percentages of IFNgamma-producing Th cells and Th1/Th2 ratio in PB correlated significantly with clinical activity score and serum IL18 levels in patients with AOSD. Increased ratio of Th1/Th2 cytokine transcripts was seen in the biopsy specimens of evanescent rash and synovitis from patients with AOSD compared with normal skin controls and patients with OA. Th cell cytokine pattern in PB and cytokine mRNA expression in synovium were similar for patients with AOSD and with RA. After 3 months' treatment, clinical remission was associated with a marked decrease in the percentages of cytokine-producing Th1 cells, but not of the Th2 cells. CONCLUSION: A predominance of Th1 cytokine may precipitate the pathogenesis of AOSD.

Adult↗

Early stage cervical cancer with negative pelvic lymph nodes: pattern of failure and complication following radical hysterectomy and adjuvant radiotherapy.

PURPOSE OF INVESTIGATION: The objective was to optimize the adjuvant treatment for patients with lymph node negative cervical cancer by analyzing patterns of failure and complications following radical hysterectomy and adjuvant radiotherapy. METHODS: From September 1992 to December 1998, 67 patients with lymph node negative uterine cervical cancer (FIGO stage distribution: 50 Ib. 17 IIa), who had undergone radical hysterectomy and postoperative adjuvant radiotherapy with a minimum of three years of follow-up were evaluated. All patients received 50-58 Gy of external radiation to the lower pelvis followed by two sessions of intravaginal brachytherapy with a prescribed dose of 7.5 Gy to the vaginal mucosa. For 21 patients with lymphovascular invasion, the initial irradiation field included the whole pelvis for 44 Gy. The data were analyzed for actuarial survival (AS), pelvic relapse-free survival (PRFS), distant metastasis-free survival (DMFS), and treatment-related complications. Multivariate analysis was performed to assess the prognostic factors. RESULTS: The respective five-year AS, PRFS, and DMFS for the 67 patients were 79%, 93% and 87%. Multivariate analysis identified two prognostic factors for AS: bulky tumor vs non-bulky tumor (p = 0.003), positive resection margin (p = 0.03). The independent prognostic factors for DMFS was bulky tumor (p = 0.003), while lymphatic permeation showed marginal impact to DMFS (p = 0.08). The incidence of RTOG grade 1-4 rectal and non-rectal gastrointestinal complication rates were 20.9% and 19.4%, respectively. The independent prognostic factor for gastrointestinal complication was age over 60 years (p = 0.047, relative risk 4.1, 95% CI 1.2 approximately 11.7). The incidence of non-rectal gastrointestinal injury for the patients receiving whole pelvic radiation and lower pelvic radiation was 28.5% and 15.2%, respectively (p = 0.25). CONCLUSION: For patients with lymph node negative cervical cancer following radical hysterectomy, adjuvant lower pelvic radiation appears to be effective for pelvic control. It is also imperative to intensify the strategies of adjuvant therapy for some subgroups of patients.

Adenocarcinoma↗

Estrogenic endocrine disruptive components interfere with calcium handling and differentiation of human trophoblast cells.

During development, calcium (Ca) is actively transported by placental trophoblasts to meet fetal nutritional and the skeletal mineralization needs. Maternal exposure to estrogenic pesticides, such as 1,1-bis(p-chlorophenyl)-2,2,2-trichloroethane (DDT) and methoxychlor (MTC), has been shown to result in reproductive disorders and/or abnormal fetal development. In this study, we have examined the effects of exposure of trophoblastic cells to MTC and DTT, in comparison to 17beta-estradiol (E2) and diethylstilbestrol (DES), to test the hypothesis that cellular Ca handling is a target for these endocrine disruptive components. Treatment with DDT, MTC, DES, or E2 increased cellular Ca uptake, and the expression of trophoblast-specific human Ca binding protein (HCaBP) was down-regulated by both MTC and DDT. Treatment with MTC, DDT, and DES inhibited cell proliferation, induced apoptosis, and suppressed expression of several trophoblast differentiation marker genes. These effects were reversed by overexpression of metallothionein IIa, a gene highly responsive to cadmium and other metals. These results strongly suggest that trophoblast Ca handling functions are endocrinally modulated, and that their alteration by candidate endocrine disruptors, such as MTC and DDT, constitutes a possible pathway of the harmful effects of these components on fetal development.

Adenosine Triphosphatases↗

Comparing whole body (18)F-2-deoxyglucose positron emission tomography and technetium-99m methylene diphosphonate bone scan to detect bone metastases in patients with breast cancer.

PURPOSE: At present, bone metastases are usually assessed using conventional technetium-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with (18)F-2-deoxyglucose (FDG-PET) can offer superior spatial resolution and improved specificity. We attempted to evaluate the usefulness of FDG-PET for detecting bone metastases in breast cancer and to compare FDG-PET results with bone scan findings. PATIENTS: The study group comprised 48 patients with biopsy-proven breast cancer and suspected of having bone metastases who underwent bone scan and FDG-PET to detect the bone metastases. The final diagnosis of bone metastases was established by operative, histopathological findings or during a clinical follow-up longer than 1 year by additional radiographs or following FDG-PET/bone scan findings showing progressive widespread bone lesions. RESULTS: A total of 127 bone lesions including 105 metastatic and 22 benign bone lesions found by either FDG-PET or bone scan were evaluated. Using FDG-PET, 100 metastatic and 20 benign bone lesions were accurately diagnosed, and using bone scan 98 metastatic and 2 benign bone lesions were accurately diagnosed. The diagnostic sensitivity and accuracy of FDG-PET were 95.2% and 94.5%, and of bone scan were 93.3% and 78.7%, respectively. CONCLUSIONS: Our findings suggest that FDG-PET shows a similar sensitivity and a better accuracy than bone scan for detecting bone metastases in patients with breast cancer.

Adult↗

Intra-thoracic failure pattern and survival status following 3D conformal radiotherapy for non-small cell lung cancer: a preliminary report.

BACKGROUND: To study the intra-thoracic failure pattern, clinical target volume (CTV) and survival status following 3D conformal radiotherapy (3DCRT) boost for non-small cell lung cancer (NSCLC). METHODS: From May 1994 through June 1998, 33 patients (26 male, seven female) with NSCLC were treated with a complete course of radiotherapy (RT) in our institute. Group A included 10 patients receiving radical operation and adjuvant postoperative RT. The other 23 patients (groups B and C) received definitive radiotherapy as local treatment. Among them there were seven cases as group B (stage I-II) and 16 cases as group C (stage III). Fifteen (15/33) patients received chemotherapy. The radiotherapy strategy constituted conventional AP/PA radiotherapy (RT) 19.8-45 Gy (median 39.6 Gy) plus 3DCRT boost 6-34.2 Gy (median 20 Gy). The median total tumor dose was 59.6 Gy (ranging from 39.8 to 64.8 Gy). Patients were followed up regularly (6/33) or until their death (27/33). Nineteen patients received follow-up chest computed tomography (CT). The relationship between intra-thoracic failure found by chest CT and the initial RT and boost RT fields was analyzed. Local failure was defined as one of the following: clinical disease progression, CXR progression or relapse noted by CT. The overall survival (OS) and local failure free survival (LFF) were obtained using the Kaplan-Meier method. RESULTS: Sixteen intra-thoracic failures were noted in 15 follow-up chest CT examinations, which included nine in-field relapses, three partial in-field relapses and four out-field relapses. The 2-year OS and LFF for groups A, B and C were 78.8/59.2, 14.2/16.7 and 6.2/7.1% respectively. RTOG grade III/IV complications included one pneumothorax (RTOG grade III). CONCLUSION: Our retrospective study showed that selective omission of contralateral mediastinal lymph node station irradiation may be appropriate in RT for NSCLC. Chest wall and pleural relapses may not be a negligible cause of intra-thoracic failure after RT for NSCLC.

Adult↗

Retrospective comparison of the AJCC 5th edition classification for nasopharyngeal carcinoma with the AJCC 4th edition: an experience in Taiwan.

OBJECTIVE: The aim of this study was to compare the new AJCC 5th edition classification system for nasopharyngeal carcinoma (NPC) with the AJCC 4th edition by re-evaluating the staging of patients treated in Taiwan. METHODS: From 1992 through 1996, 117 NPC patients without distant metastasis were treated using complete courses of radiotherapy. All patients had complete CT examinations of the nasopharynx and neck. Each patient was re-staged according to the 5th edition of the AJCC classification system. Their overall survival (OS), loco-regional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS) and disease-free survival (DFS) were compared between the two staging systems, using the Kaplan-Meier method, log-rank test, Wilcoxon test and Cox proportional hazard model. RESULTS: After a median follow-up of 58.3 months, the 5-year OS for stage I, II, III and IV was 88, 86, 61 and 48%, respectively, according to the new staging. A more even distribution of patients was noted among the patients classified according to the AJCC 5th edition than the 4th edition. The distribution of stages I, II, III and IV was 13.7, 37.6, 15.4 and 33.3%, respectively, using the new staging system, whereas it was 0.8, 14.5, 20.5 and 64.2%, respectively, using the old staging system. More statistically significant differences among 5th edition stages and T classifications than the 4th edition were also noted. CONCLUSIONS: The 5th edition of the AJCC staging system appears to have a more even distribution of patients and more statistically significant differences in predicting prognosis than the 4th edition, mostly in stages and T classification.

Disease-Free Survival↗

Oxidized frying oil up-regulates hepatic acyl-CoA oxidase and cytochrome P450 4 A1 genes in rats and activates PPARalpha.

Oxidized LDL (oxLDL) and its component hydroxy fatty acids were shown to activate peroxisome proliferator-activating receptor alpha (PPARalpha) and gamma (PPARgamma). To test the hypothesis that lipid oxidation products in oxidized frying oil (OFO) can activate PPARalpha and up-regulate its target genes, a feeding experiment and a transactivation experiment were conducted. Based on a 2 x 2 factorial design, four groups of Sprague-Dawley male weanling rats were fed diets containing either high (20 g/100 g, HO and HF) or low (5 g/100 g, LO and LF) levels of oxidized frying soybean oil (HO and LO) or fresh soybean oil (HF and LF) for 6 wk. The OFO sample was prepared by frying wheat dough sheets in soybean oil at 205 +/- 5 degrees C for 24 h. OFO dose dependently and significantly increased (P < 0.05) mRNA of acyl-CoA oxidase (ACO) and cytochrome P(450) 4A1(CYP4A1) in liver of rats. Dietary OFO also dose dependently increased liver microsomal CYP4A protein (P < 0.05). The activity of hepatic ACO of the HO group was sixfold that of the HF group (P < 0.05). Plasma total lipids, liver triglycerides, cholesterol and total lipids were reduced in rats fed the LO and HO diets (P < 0.05). Through the ligand binding domain of PPARalpha, the hydrolyzed OFO enhanced the expression of alkaline phosphatase (ALP) reporter gene to a significantly greater extent (P < 0.05) than the hydrolyzed fresh soybean oil in a transactivation assay using a clone of CHO K1 cells stably expressing Gal4-PPARalpha chimeric receptor and UAS4-ALP reporter. The results support our hypothesis that dietary OFO, by activating PPARalpha, up-regulates the expression of PPARalpha downstream genes and alters lipid metabolism in rats.

Acyl-CoA Oxidase↗

Recurrent fuzzy neural network control for piezoelectric ceramic linear ultrasonic motor drive.

In this study, a recurrent fuzzy neural network (RFNN) controller is proposed to control a piezoelectric ceramic linear ultrasonic motor (LUSM) drive system to track periodic reference trajectories with robust control performance. First, the structure and operating principle of the LUSM are described in detail. Second, because the dynamic characteristics of the LUSM are nonlinear and the precise dynamic model is difficult to obtain, a RFNN is proposed to control the position of the moving table of the LUSM to achieve high precision position control with robustness. The back propagation algorithm is used to train the RFNN on-line. Moreover, to guarantee the convergence of tracking error for periodic commands tracking, analytical methods based on a discrete-type Lyapunov function are proposed to determine the varied learning rates of the RFNN. Then, the RFNN is implemented in a PC-based computer control system, and the LUSM is driven by a unipolar switching full bridge voltage source inverter using LC resonant technique. Finally, the effectiveness of the RFNN-controlled LUSM drive system is demonstrated by some experimental results. Accurate tracking response and superior dynamic performance can be obtained because of the powerful on-line learning capability of the RFNN controller. Furthermore, the RFNN control system is robust with regard to parameter variations and external disturbances.

Journal Article↗

Photic signaling by cryptochrome in the Drosophila circadian system.

Oscillations of the period (per) and timeless (tim) gene products are an integral part of the feedback loop that underlies circadian behavioral rhythms in Drosophila melanogaster. Resetting this loop in response to light requires the putative circadian photoreceptor cryptochrome (CRY). We dissected the early events in photic resetting by determining the mechanisms underlying the CRY response to light and by investigating the relationship between CRY and the light-induced ubiquitination of the TIM protein. In response to light, CRY is degraded by the proteasome through a mechanism that requires electron transport. Various CRY mutant proteins are not degraded, and this suggests that an intramolecular conversion is required for this light response. Light-induced TIM ubiquitination precedes CRY degradation and is increased when electron transport is blocked. Thus, inhibition of electron transport may "lock" CRY in an active state by preventing signaling required either to degrade CRY or to convert it to an inactive form. High levels of CRY block TIM ubiquitination, suggesting a mechanism by which light-driven changes in CRY could control TIM ubiquitination.

Animals↗

The prediction of late rectal complications following the treatment of uterine cervical cancer by high-dose-rate brachytherapy.

PURPOSE: This study aimed to correlate patient, treatment, and dosimetric factors with the risk of late rectal sequelae in patients with uterine cervical cancer treated with external beam radiation therapy (EBRT) and high dose rate intracavitary brachytherapy (HDRICB). METHODS AND MATERIALS: From September 1992 to December 1995, a total of 128 patients with uterine cervical cancer, who were treated and survived more than 12 months, were evaluated. After EBRT with 40-44 Gy/20-22 Fr/4-5 weeks to the whole pelvis, the dose was boosted up to 54-58 Gy with central shielding for patients with bilateral parametria of Stage IIb or greater. HDRICB consisted of three to four insertions at doses of 5-7.2 Gy (to Point A) at intervals of 1 week. Patient and treatment factors were analyzed using logistic regression analysis and the cumulative rectal biologic equivalent dose (CRBED) was calculated. RESULTS: After 30-75 months of follow-up (median, 43 months), 38 patients (29.7%) had late rectal sequelae. Patients who had Stage IIb-IVa disease, cumulative rectal dose (external RT + total ICRU rectal dose) greeater than 65 Gy, or age greater than 70 years had a high risk of developing late rectal sequelae. When 110 Gy was used as the cut-off value, 19.6% (10 of 51) of patients whose CRBED was less than 110 Gy had rectal complications, while 36.4% (28/77) of patients whose CRBED was greater than 110 Gy developed rectal complications. CONCLUSION: Risk factors of late rectal complications were advanced stage, age greater than 70 years, and cumulative rectal dose of greater than 65 Gy.

Adult↗

Lead in the southern East China Sea.

At present, in most oceans the lead (Pb) biogeochemical cycling has been disturbed by anthropogenic Pb through atmospheric input. The Pb concentrations in the upper water positively correlate with atmospheric input fluxes of Pb. The North Pacific is affected greatly by atmospheric substances via long-range transport from eastern Asia, especially from Mainland China. Mainland China may export considerable amounts of pollutants into the seas via rivers and the atmosphere owing to its recent fast growth in industry and economy. The East China Sea lies in an important geographical position--a transit between Mainland China and the western North Pacific. However, no data are available for seawater concentrations of Pb, a representative element with anthropogenic origin. In this work seawater samples from both 5 and 30-50 m water layers of 15 stations occupied over a cyclonic eddy in the southern East China Sea were analyzed for particulate Pb (PPb) and dissolved Pb (DPb). The Mean concentration of DPb (approximately 128 ng/l) in the southern East China Sea upper waters (< or = 50 m) is approximately several times higher than those in the Pacific; the high DPb concentrations in the southern East China Sea waters correspond to much higher atmospheric supplies of Pb to the East China Sea. Thus, this study partly fills the 'data gap' of the marginal seas. Also, it indicates that the East China Sea may be considerably contaminated by deposited polluted aerosols. Spatial distributions of DPb in the surface water show a tendency of increasing concentrations with distance offshore, that depends on the magnitudes of atmospheric Pb inputs and on particle scavenging processes. In contrast to DPb, spatial distributions of PPb basically display an 'omega'-like picture and a tendency of decreasing concentrations with distance offshore. These are related to riverine and scavenging sources and to the drive by the eddy. Additionally, the residence times of DPb in the surface water were estimated to be about 2 years, agreeing well with the reported data.

Lead↗

Oscillation and light induction of timeless mRNA in the mammalian circadian clock.

Circadian rhythms in Drosophila melanogaster depend on a molecular feedback loop generated by oscillating products of the period (per) and timeless (tim) genes. In mammals, three per homologs are cyclically expressed in the suprachiasmatic nucleus (SCN), site of the circadian clock, and two of these, mPer1 and mPer2, are induced in response to light. Although this light response distinguishes the mammalian clock from its Drosophila counterpart, overall regulation, including homologous transcriptional activators, appears to be similar. Thus, the basic mechanisms used to generate circadian timing have been conserved. However, contrary to expectations, the recently isolated mammalian tim homolog was reported not to cycle. In this study, we examined mRNA levels of the same tim homolog using a different probe. We observed a significant (approximately threefold) diurnal variation in mTim expression within mouse SCN using two independent methods. Peak levels were evident at the day-to-night transition in light-entrained animals, and the oscillation persisted on the second day in constant conditions. Furthermore, light pulses known to induce phase delays caused significant elevation in mTim mRNA. In contrast, phase-advancing light pulses did not affect mTim levels. The mTim expression profile and the response to nocturnal light are similar to mPer2 and are delayed compared with mPer1. We conclude that temporal ordering of mTim and mPer2 parallels that of their fly homologs. We predict that mTIM may be the preferred functional partner for mPER2 and that expression of mTim and mPer2 may, in fact, be driven by mPER1.

Animals↗

Phylogeny and evolution of the Drosophila nasuta subgroup based on mitochondrial ND4 and ND4L gene sequences.

The sequences of the mitochondrial ND4 gene (1339 bp) and the ND4L gene (290 bp) were determined for all the 14 extant taxa of the Drosophila nasuta subgroup. The average A + T content of ND4 genes is 76.5% and that of ND4L genes is 83.5%. A total of 114 variable sites were scored. The ND4 gene sequence divergence ranged from 0 to 5.4% within the subgroup. The substitution rate of the ND4 gene is about 1.25% per million years. The base substitution of the genes is strongly transition biased. Neighbor-joining and parsimony were used to construct a phylogeny based on the resultant sequence data set. According to these trees, five distinct mtDNA clades can be identified. D. niveifrons represents the most diverged lineage. D. sulfurigaster bilimbata and D. kepulauana form two independent lineages. The other two clades are the kohkoa complex and the albomicans complex. The kohkoa complex consists of D. sulfurigaster sulfurigaster, D. pulaua, D. kohkoa, and Taxon-F. The albomicans complex can be divided into two groups: D. nasuta, D. sulfurigaster neonasuta, D. sulfurigaster albostrigata, and D. albomicans from Chiangmai form one group; and D. pallidifrons, Taxon-I, Taxon-J, and D. albomicans from China form the other group. High genetic differentiation was found among D. albomicans populations. Based on our phylogenetic results, we hypothesize that D. niveifrons diverged first from the D. nasuta subgroup in Papua New Guinea about 3.5 Mya. The ancestral population spread to the north and when it reached Borneo, it diversified sequentially into the kohkoa complex, D. s. bilimbata, and D. kepulauana. About 1 Mya, another radiation occurred when the ancestral populations reached the Indo-China Peninsula, forming the albomicans complex. Discrepancy between morphological groupings and phylogenetic results suggests that the male morphological traits may not be orthologous.

Animals↗

Stepwise chromosome evolution in Drosophila albomicans.

A 'stepwise chromosome evolution model' is proposed to elaborate the two stages of the sex chromosome evolution of Drosophila albomicans. To explain the occurrence of both a 3-X and a 3-Y in this species it is proposed that these chromosomes evolved sequentially. The selection forces acting in the two stages are different. The genic composition in the first fused sex chromosome of D. albomicans was supposed to be selectively superior to the primitive unfused chromosomes, thus the fused chromosome could overcome the meiotic structural incompatibility and be maintained in the population during the first stage. When the second fusion occurred, the newly fused sex chromosome was preferentially selected, as it could provide a meiotic pairing partner for the first fusion. The fused sex chromosomes were eventually fixed in the population. Based on this model, we tried to determine which fused chromosome, 3-X or 3-Y, established first. The karyotyping result of four experimental hybrid populations showed that the fused 3-X, as opposed to 3-Y, chromosome has higher fitness values. However, without the coexistence of 3-X, 3-Y is excluded rapidly. Therefore, 3-X is likely to be the first fused chromosome in the stepwise chromosome evolution model. The formation and fixation of the fused 3-Y chromosome occurred subsequently.

Animals↗

Effect of ionizing radiation on liver mitochondrial respiratory functions in mice.

OBJECTIVE: To investigate the radiation effect on mitochondria of the mouse liver in vivo. METHODS: Livers of BALB/c mice were squeezed out through openings cut on the upper abdomen and radiation doses were delivered only to the livers. Radiation effects on the structure and function of liver mitochondria were evaluated from both respiratory control ratio (RCR) and ADP/O (adenosine 5'-diphosphate/oxygen) ratio supported by two substrates, succinate and glutamate/malate mixtures. RESULTS: The data showed that both state 3 and state 4 respiratory rates were significantly decreased concomitantly with the increase of radiation dose up to 20 Gy. Succinate-supported, but not glutamate/malate-supported, respiratory control ratio, was also decreased with the increase of radiation dose. ADP/O ratios measured from the support of both succinate and glutamate/malate were not changed by gamma-radiation. This differential radiation damage indicated that respiratory control ratio was more vulnerable to radiation than oxidative phosphorylation. CONCLUSIONS: Although the functional integrity of ATP synthetic machinery of the mitochondria was not perturbed by ionizing radiation under 20 Gy, the structural integrity of mitochondrial membrane might be affected by ionizing radiation at a dose-dependent manner.

Animals↗

Effects of cadmium on trophoblast calcium transport.

Maternal exposure to cadmium (Cd) during pregnancy has been linked to low fetal birthweight, which may be attributed to placental damage and/or dysfunction in nutrient transport. Previous studies have suggested that Cd is accumulated in the placenta, and that placental transport of calcium (Ca) and zinc (Zn) is perturbed by Cd. To investigate the mechanism of Cd perturbation of Ca transport, we used JEG-3, a human choriocarcinoma cell line which exhibits trophoblastic properties, to analyse Cd effects in vitro. Treatment with Cd at low, physiologically relevant concentrations (e.g. 0.04 microM) did not result in obvious changes in cell morphology or integrity, whereas higher concentrations (> or = 0.16 microM) affected cell integrity. With lower concentrations of Cd treatment for 24 h, activities of cellular Ca uptake and transport, and Ca2+ binding were decreased, and intracellular [Ca2+] ([Ca2+]i) profile was also altered; however, membrane-associated Ca(2+)-activated ATPase activity remained relatively unchanged. Interestingly, cellular Ca uptake activity was unaffected by short-term (30 min) Cd pretreatment. The 24-h Cd treatment also resulted in elevated expression of the metal-binding protein, metallothionein, whereas the expression of a trophoblast-specific cytosolic Ca(2+)-binding protein (HCaBP) was drastically reduced. These results strongly suggest that Cd exposure significantly compromises the Ca handling ability of trophoblastic cells; this effect is probably not due to perturbations in Ca channel or membrane Ca pump activities, but rather a consequence of alterations in subcellular, cytosolic Ca2+ binding activities.

Adenosine Triphosphatases↗