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G Liu

Publications and source records attributed to G Liu.

At least 523 records · Page 29Linked to original sources

Synaptic transmission at single visualized hippocampal boutons.

We have used a focal stimulation method to study neurotransmission at synapses onto hippocampal pyramidal neurons in cultures derived from neonatal rats. Single functional boutons were visualized by activity-dependent preloading with the fluorescent dye FM1-43, then focally stimulated by localized application of elevated K+/Ca2+ solution via a puffer pipette, while postsynaptic currents were recorded under whole cell voltage clamp (Liu and Tsien, 1995). This paper gives a detailed description of the main properties of this experimental system and of information it has provided about fundamental properties of hippocampal synapses. Most of the experiments focused on excitatory postsynaptic currents (EPSCs), but preliminary recordings of inhibitory events (IPSCs) are also reported here. The unitary EPSCs at individual synapses varied greatly in amplitude, but were relatively uniform in their time course. The frequency of the synaptic events was greatly reduced by lowering the external Ca2+ concentration or by application of baclofen, a GABAB receptor agonist. Frequent repetitive stimulation produced a decline in the incidence of EPSCs that was readily reversed upon rest. We attribute the decline to exhaustion of a pool of available vesicles; typically, recovery proceeded with a time constant of approximately 40 sec (23 degrees C), and involved a vesicular pool capable of generating approximately 90 EPSCs without recycling. While synaptic currents were broadly distributed in amplitude (Bekkers et al., 1990), this distribution was remarkably similar at multiple synapses on a given postsynaptic neuron. The median synaptic current amplitude varied 4-fold across different cells, decreasing markedly with increasingly dense synaptic innervation. The implications of these results for cellular signal processing and quantal analysis are discussed.

Animals↗

Antioxidant and cytotoxic tocopheryl quinones in normal and cancer cells.

We found previously that [d]-alpha-tocopherol (alpha-T) and [d]-gamma-tocopherol (gamma-T) are lipid antioxidants (thiobarbituric acid test) in model systems containing arachidonic acid (AA), cumene hydroperoxide, and Fe3+ and in smooth muscle cell (SMC) cultures challenged with AA. We now show that [d]-alpha-tocopherylquinone (alpha-TQ), [d]-delta-tocopherylquinone (delta-TQ), and [d]-gamma-tocopherylquinone (gamma-TQ) are antioxidants at low concentrations and prooxidants at high concentrations in the model system. Prooxidant activity is greater with gamma-TQ than either alpha-TQ or delta-TQ. Low concentrations of alpha-TQ, delta-TQ, and gamma-TQ are also antioxidants in SMC cultures challenged with AA. Unlike alpha-TQ, partially substituted gamma-TQ and glutathione (GSH) form a Michael adduct which has been purified and characterized. We found previously that alpha-T, gamma-T, and alpha-TQ are mitogenic in SMC. We now report that both delta-TQ and gamma-TQ but not alpha-TQ show concentration-dependent cytotoxicity (changes in morphology, propidium iodide stain) in SMC cultures. Cytotoxicity is greater with gamma-TQ than delta-TQ. An acute lymphoblastic leukemia (ALL) cell line shows greater chemosensitivity (MTT and Neutral Red assays) to gamma-TQ than to either doxorubicin (DOX) or vinblastine (VLB). An ALL cell line resistant to both DOX and VLB retains the same chemosensitivity to gamma-TQ as the drug-sensitive ALL cell line. ALL cell lines are unaffected by either alpha-TQ or the GSH Michael adduct of gamma-TQ. These data show that partially substituted tocopheryl quinones capable of forming Michael adducts are potential chemotherapeutic agents for multidrug-resistant cancer cells.

Animals↗

Thyroid stimulating hormone and N6-2'-O-dibutyryladenosine 3'-5'-cyclic monophosphate decrease 110,000-130,000 M(r) tyrosine-phosphorylated substrate in rat thyroid cells.

By immunoblotting using monoclonal antibodies against phosphotyrosine, thyroid stimulating hormone (TSH)-induced changes in tyrosine phosphorylation of intracellular proteins in earlier passages of rat thyroid cells (FRTL-5) were studied. TSH and N6-2'-O-dibutyryladenosine 3'-5'-cyclic monophosphate (Bt2cAMP) decreased the phosphotyrosine content of 110,000-130,000 M(r) substrate (p120) in parallel with a morphological change in FRTL-5 cells. Insulin-like growth factor-I (IGF-I) or phorbol 12-myristate 13-acetate (PMA) only showed an attenuated reaction compared with that of TSH or Bt2cAMP. Further, sodium orthovanadate (a protein tyrosine phosphatase inhibitor) could not inhibit this reaction. These data suggest possible inhibitory effects of TSH and adenosine 3'-5'-cyclic monophosphate (cAMP) on tyrosine kinases that act on this substrate.

Animals↗

Aortic dissection in giant-cell arteritis.

Twenty-three cases of aortic dissection in patients with giant-cell arteritis are reviewed and an additional case is reported. Forty-six percent presented catastrophically with aortic dissection and no prior history of giant cell arteritis. Eighty percent died within 2 weeks of the event; four patients had successful surgical grafts. There was diffuse involvement of the aorta with giant cells in 89%, but dissecting tears occurred primarily in the proximal aorta in 85% of cases. The majority of cases with a preceding history of giant cell arteritis were on low doses of steroid or on no treatment at the time of dissection, and the median erythrocyte sedimentation rate of these patients was 62 mm/h (range 21-98). Evidence of some form of hypertension, whether acute or chronic, mild or severe, was found in 77% of patients. Inadequate treatment of giant-cell arteritis and underlying hypertension (treated or untreated) are potential factors leading to aortic dissection in these patients.

Aged↗

Simultaneous determination of copper and zinc in the hair of children by pH gradient construction in a flow-injection system.

A flow-injection method is described for the simultaneous determination of copper and zinc with a single detector using the pH gradient technique. Zincon is used as the colour reagent for the spectrophotometric determination. The linear range for the determination of zinc is 0.4-12 micrograms ml-1 and for copper is 0.1-3.0 micrograms ml-1. About 20-30 samples can be determined in one hour. The proposed method has been applied to the determination of zinc and copper in childrens' hair.

Child↗

Growth related traits in body weight selected lines and their crosses reared under different nutritional regimens.

1. Four populations--two that had undergone 37 generations of selection for high (HH) and low (LL) body weight, and reciprocal crosses between them (HL and LH) were fed two diets differing in protein and energy. Diet A, under which selection had been made, contained 200 g protein and 11.23 MJ/kg. Diet E contained 240 g protein and 13.16 MJ/kg. 2. Body weight and feed efficiency were measured weekly from hatch to 56 d of age at which time oesophagus, abdominal fat pad, heart, liver and lungs were removed and weighed. At 35 d of age chicks were inoculated with sheep erythrocytes (SRBC) and antibody titre was measured 6 d later. 3. Chicks fed diet E were heavier than those fed diet A. HH chicks were heavier than LL chicks with HL and LH chicks intermediate to the parental lines. LH chicks were heavier than HL ones reflecting large maternal effects. 4. Food efficiencies among stocks and diets were consistent with those for body weight, with HH > LH > HL > LL and E > A. Relative differences between diets were similar across ages and heterosis for food efficiency was about 15%. 5. Relative to body weight, oesophagus and liver weights were heavier in chickens fed diet A than fed diet E. The pattern reversed for abdominal fat pad. 6. Antibody to SRBC antigen was greater in the crosses than in line HH and in cross HL than line LL, with heterosis of 70%.

Aging↗

Estimating parametric survival model parameters in gerontological aging studies: methodological problems and insights.

Studies of the biology of aging (both experimental and evolutionary) frequently involve the estimation of parameters arising in various multi-parameter survival models such as the Gompertz or Weibull distribution. Standard parameter estimation methodologies, such as maximum likelihood estimation (MLE) or nonlinear regression (NLR), require knowledge of the actual life spans or their explicit algebraic equivalents in order to provide reliable parameter estimates. Many fundamental biological discussions and conclusions are highly dependent upon accurate estimates of these survival parameters (this has historically been the case in the study of genetic and environmental effects on longevity and the evolutionary biology of aging). In this article, we examine some of the issues arising in the estimation of gerontologic survival model parameters. We not only address issues of accuracy when the original life-span data are unknown, we consider the accuracy of the estimates even when the exact life spans are known. We examine these issues as applied to known experimental data on diet restriction and we fit the frequently used, two-parameter Gompertzian survival distribution to these experimental data. Consequences of methodological misuse are demonstrated and subsequently related to the values of the final parameter estimates and their associated errors. These results generalize to other multiparametric distributions such as the Weibull, Makeham, and logistic survival distributions.

Aging↗

Mammalian endo-exonuclease activity and its level in various radiation sensitive cell lines.

The levels of endo-exonuclease in various mammalian cell lines were examined. While the expression of the endo-exonuclease during cell growth behaved exactly the same as the pattern observed in lower eukaryotes, the amount of activity was found to be reduced in the radiosensitive Chinese hamster ovary (CHO) xrs-5 and various human AT, AT-5 and NE-1 cells when compared to the radionormal CHO K1 and human HeLa cell lines. The reduced endo-exonuclease activity in these cells was due to a decreased amount of protein as demonstrated with the immuno-blot method. The results presented here suggest that endo-exonuclease may be one of the many proteins whose expression is regulated by genes coding for xrs-5 in CHO and AT in humans.

Animals↗

Methotrexate therapy of psoriasis: differential sensitivity of proliferating lymphoid and epithelial cells to the cytotoxic and growth-inhibitory effects of methotrexate.

Although methotrexate (MTX) is one of the most clinically effective therapies employed to treat psoriasis, the mechanism by which low-dose MTX acts to modulate the hyperplasia of psoriasis, leading to the restoration of clinically normal skin, is only partially understood. MTX has been considered a cytotoxic agent that mediates its effect primarily on proliferating or cycling epidermal cells. Recently, proliferating lymphoid cells have been identified in psoriatic lesions, raising the possibility that proliferating lymphoid cells could be another target cell that is killed by MTX. In this study, we examined the growth-inhibitory and cytotoxic effects of MTX on proliferating lymphoid cells [THP-1 (macrophage), and MOLT-4 (T cell)], epithelial cells (HeLa, and HaCat), and normal human keratinocytes (NHK) in vitro. The proliferating cells were exposed to MTX for 24 h, and placed in fresh media to mimic the transient MTX blood levels that result from once-weekly therapy. THP-1 and MOLT-4 were found to be 10-100 times more sensitive to the cytotoxic effects of MTX than were HeLa and HaCat, and more than 1000 times more sensitive than primary human keratinocytes. At MTX concentrations that would be expected to occur in vivo during once-weekly therapy, a large percentage (> 95%) of proliferating lymphoid targets would be killed, and only a small percentage (< 10%) of proliferating epidermal cells would be affected. This in vitro data suggests that in psoriasis proliferating lymphoid cells are more likely than epithelial cells to be a major cellular target of MTX in vivo.

Cell Division↗

Increased Ca2+ and myosin phosphorylation, but not calmodulin activity in sensitized airway smooth muscles.

The increased shortening velocity and capacity of airway smooth muscle (ASM) from ragweed pollen-sensitized dogs, which may be responsible for its in vivo airway hyperresponsiveness, have been shown to be associated with higher actomyosin adenosinetriphosphatase activity and greater level of phosphorylation of the 20-kDa myosin light-chain (MLC20) at rest and during contraction. Current studies show that the elevated level of phosphorylation may be the result of an increased myosin light-chain kinase (MLCK) activity due to excessive quantity of MLCK. There were no significant changes in total activity of calmodulin, a protein that binds and activates MLCK, in sensitized dog ASM (SASM) compared with control ASM (CASM). When normalized to the relative calmodulin content in the tissues, the specific calmodulin activities (means +/- SE) in sensitized tracheal smooth muscle (STSM) and sensitized bronchial smooth muscle (SBSM) and in their controls were not different (STSM 0.359 +/- 0.117, CTSM 0.339 +/- 0.136. SBSM 0.201 +/- 0.098, and control bronchial smooth muscle 0.213 +/- 0.056 nmol Pi.calmodulin content-1.min-1, respectively). Intracellular Ca2+ levels indicated by fura 2 fluorescent dye remained unaltered in SASM. We conclude that airway hyperresponsiveness may result from higher MLCK content in SASM rather than from changes in Ca(2+)-calmodulin activities, which is an example of alteration in Ca2- sensitivity of ASM.

Animals↗

Identification of gastrin as a growth peptide in human pancreatic cancer.

The present study reports the first evidence that the gastrointestinal peptide gastrin stimulates the growth of several human pancreatic cancer cells in culture and in tumors transplanted to nude mice. Gastrin promoted growth of all cell lines tested at a dose comparable to the binding affinity, providing evidence for a physiologically relevant receptor. The stimulatory effects of gastrin were blocked by the CCK-B/gastrin receptor antagonist L-365,260 and not by the CCK-A receptor antagonist L-364,718. Growth of PANC-1 cells in culture were inhibited by L-365,260, suggesting that gastrin is tonically produced by PANC-1 cells for regulation of growth. Athymic nude mice bearing PANC-1 xenografts were treated for 24 days subcutaneously with either 1% bovine serum albumin (diluent), pentagastrin (1 mg/kg), or L-365,260 (1 mg/kg) twice daily. Tumors from the pentagastrin-treated mice were found to weigh more and have greater protein and DNA content than controls, whereas these values were all decreased in tumors of L-365,260-treated mice. Receptor binding capacity changed in tumors of animals treated with the peptide or antagonist, suggesting a regulatory process. Gastrin immunoreactivity was detected in a transplanted PANC-1 human tumor. These results identify gastrin as a potent trophic peptide that actively stimulates growth of human pancreatic cancer and does so through a CCK-B/gastrin-like receptor.

Animals↗

Intubation of weight-selected chicks with soybean oil or residual yolk: effect on early growth and development.

Experiments were conducted to study the role of residual yolk on growth and development of chicks during the 1st wk after hatch. Surgical removal of the yolk sac at hatch reduced early body weight gains. Intubating chicks with a mixture of soybean meal and soybean oil or with residual yolk obtained from chicks at hatch increased body weights and enhanced development of the liver and pancreas. Whereas intubation with residual yolk reduced absorption of yolk sac contents, absorption was similar for chicks that consumed mash ad libitum or were intubated with the soybean meal-soybean oil diet. After cessation of yolk intubation, absorption of residual yolk resumed. Removal of the yolk sac decreased amylase and lipase activity in the pancreas. In the intestinal chyme, activity of amylase, trypsin, and chymotrypsin was reduced by yolk sac removal. Intubation with yolk increased enzyme activity (amylase excepted) in the pancreas or intestinal chyme only in chicks that had their yolk sacs removed. There was evidence that contents of the yolk sac did not enter the intestine via the yolk stalk, but were absorbed directly via the blood.

Aging↗

Correlated responses to long-term divergent selection for eight-week body weight in chickens: growth, sexual maturity, and egg production.

Thirty-six generations of divergent selection for BW at 8 wk of age (BW8) resulted in approximately an eightfold difference between the high (HWS) and low (LWS) lines for this trait. Correlated traits included BW at 4, 24, and 38 wk of age (BW4, BW24, BW38, respectively), age at first egg (AFE), and percentage hen-day egg production (HDP). Responses of BW4 followed the same pattern as that for the selected trait, with the response about five times greater during the first 18 than the last 18 generations of selection in Line HWS and less than two times greater in Line LWS. For BW24 and BW38, correlated responses were greater for LWS than for HWS females without feed restriction, suggesting changes in growth curves after selection age. Although AFE was delayed in both lines, the delay was greater in Line LWS (some individuals of which were anorexic) than in Line HWS and greater in the second half than the first half of the experiment. For pullets that commenced lay, HDP declined slightly in both lines. Correlations between BW at 4, 8, 24, and 38 wk of age were moderate to high and positive in both lines. When feed intake was restricted in Line HWS, however, there were no correlations of BW4 or BW8 with BW24 or BW38. Correlations between AFE and BW at all ages were negative in Line LWS. In Line HWS there were negative correlations of AFE with BW24 and with BW38. Relaxed lines, established periodically during the experiment, were satisfactory monitors of environmental influences for primary and correlated traits.

Animals↗

Irrigation and traction therapy for open fracture with large-sized full-thickness skin-deficit and severely infected wound.

In this paper the results of skeletal traction and irrigation therapy (STIT) used for open fracture complicated with large-sized full-thickness skin-deficit and infection wounds (OFIW) were presented. Fourteen patients of OFIW were treated by the plaster cast and wound dressing (PCWD), and 30 patients of OFIW were treated by STIT. The results indicated that after one week of treatment, the white blood cell count in the STIT group, compared to 17.6 +/- 1.0 x 10(9)/L from before treatment, returned to 8.8 +/- 0.8 x 10(9)/L, and in contrast, the cell count of the PCWD group was about 13.0 +/- 1.4 x 10(9)/L. All of wound exudate culture in the STIT group was negative, and those of 7 cases (7/14) in PCWD group were positive (P < 0.01). The symptoms and signs such as pain, fever and septic exudate on the wound in the STIT group were much milder than those in the PCWD group. There were 5 cases (35.7%) of toxicemia and septicemia, 2 cases (14.3%) of osteomyelitis, 2 cases (14.3%) of amputation, 1 case (7.1%) of delayed union and 3 cases (21.4%) of malunion in the PCWD group, and no complications in the STIT group.

Adolescent↗

[PCNA expression and AgNORs image analysis as factors in judging the prognosis of lung cancer].

The expression of PCNA and AgNORs count or AgNORs' area in 86 cases of primary lung cancer and 10 cases of inflammatory pseudotumor were studied by S-P immunostaining of monoclonal antibody (PC-10) and image analysis system. The results showed that the proliferating index (PI) of PCNA positive cells was closely related to AgNORs count and AgNORs' area measured. Both were correlated with the histological type, and the TNM status, decreased with the increasing degree of histological differentiation. Survival analysis showed that the PI and the results of AgNORs image analysis in surgical patients who survived over 5 years were significantly lower than those who survived less than 3 years. The results suggest that immunostaining of PCNA and AgNORs image analysis are useful in judging the malignant degree and the prognosis of primary lung cancer.

Adenocarcinoma, Bronchiolo-Alveolar↗