Biomedical subjects

Y Tao

Publications and source records attributed to Y Tao.

At least 163 records · Page 9Linked to original sources

PubMed1993

The role of amino acids in ApoB100 synthesis and catabolism in human HepG2 cells.

The object of this study was to examine the effects of extracellular amino acids on hepatic apoB100 metabolism using a transformed human liver cell line (HepG2) as a hepatocyte model. The data demonstrate that reduced extracellular amino acids resulted in marked increases in apoB100 concentrations in the medium (87 +/- 10% increase; p < 0.002). These data contrast with the effects of amino acids on secretion of total hepatic protein into the medium, which increased by 541 +/- 83% at 5.5 mg/ml amino acids compared to the low (0.5 mg/ml) amino acid medium (p < 0.01), pointing to a positive relationship between the concentration of amino acids in the medium and overall secretion of protein by the HepG2 cells. No significant effect of medium amino acid concentration on intracellular synthesis of cholesterol ester, cholesterol, triglyceride, or apoA1 secretion was evident. Amino acids also affected the activity of the low density lipoprotein pathway: at lower medium amino acid concentration, specific cell-associated radioactivity and cellular degradation were increased (117 +/- 24 and 233 +/- 13% at 0.5 versus 5.5 mg/ml amino acids, respectively). Pulse-chase analysis demonstrated that there was no difference in secretion efficiency of apoB (36 +/- 6 versus 46 +/- 8% in low versus high amino acid medium, respectively), but that the initial amount of [3H]apoB synthesized was greater in the low amino acid medium (10.5 +/- 3.8 versus 5.7 +/- 1.7 x 10(3) dpm [3H]apoB/mg of cell protein; p < 0.05). In contrast, the initial amount of [3H]albumin synthesized was much greater in the high amino acid medium (26.6 +/- 5.0 versus 54.6 +/- 19.0 x 10(3) dpm [3H]albumin/mg of cell protein in low versus high amino acid medium, respectively; p < 0.05). Slot blot analysis of apoB mRNA was 87 +/- 22% higher in lower amino acid medium as compared to the high amino acid medium (p < 0.01). These results demonstrate that amino acids have a profound negative regulatory effect on apoB synthesis and secretion and may shed light on the pathogenesis of some clinical dyslipidemias such as the increased plasma apoB levels in patients treated with continuous ambulatory peritoneal dialysis.

Albumins↗

PubMed1993

Prognostic factors in patients with metastatic malignant melanoma. A multivariate analysis.

BACKGROUND: Current methods to predict survival in patients with advanced, metastatic melanoma are limited. To determine clinical prognostic factors that accurately predict survival in patients with metastatic melanoma, a retrospective analysis was performed. METHODS: Clinical, hematologic, and biochemical pretreatment parameters from 284 patients entered on 18 Phase I and II clinical trials were analyzed to determine their prognostic effect on survival. A multivariate parametric regression based on the Weibull distribution was derived to estimate survival. RESULTS: Multivariate Weibull survival regression analysis showed that a simple model using the logarithm of the pretreatment values of lactate dehydrogenase and serum albumin, dichotomized as high and low, significantly and adequately predicted survival. A more complex multivariate model was also derived that involved the pretreatment platelet count, visceral organ involvement, and gender as additional factors. However, a larger study is needed to statistically validate such a model. CONCLUSIONS: The pretreatment values of serum lactate dehydrogenase and albumin are independent prognostic factors for survival in patients with metastatic melanoma. These two factors can be used to estimate survival of patients with advanced, metastatic melanoma and should be considered when designing melanoma trials in which survival is an endpoint.

Adult↗

PubMed1993

Platelet-activating factor induces collagenase expression in corneal epithelial cells.

Platelet-activating factor (PAF), a potent lipid mediator involved in inflammatory and immune responses, accumulates rapidly in response to injury in a variety of tissues, including the corneal epithelium. However, the precise role of this compound in the cascade of events following insult has not been defined. Here we examined the effect of PAF on gene expression in the epithelial cells of rabbit corneas in organ culture. We found that incubation with 100 nM methylcarbamoyl PAF, a nonhydrolyzable analog of PAF, produced rapid transient 2.8- and 3.5-fold increases in the expression of c-fos and c-jun, respectively, at 1 hr, followed by increased expression of the collagenase type I gene beginning at 3 hr and peaking at 14-fold by 8 hr. Addition of the protein-synthesis-inhibitor cycloheximide superinduced c-fos and c-jun, strongly potentiating the PAF effect, but inhibited the induction of collagenase type I expression, suggesting the existence of a transcriptional factor linking the two events. BN-50730, a selective antagonist of intracellular PAF-binding sites, blocked the expression of the immediate-early genes as well as the increase in collagenase type I mRNA. Our results suggest that one of the functions of PAF may be to enhance the breakdown of the extracellular matrix as a part of the remodeling process during corneal wound healing after injury. Pathologically, a PAF-induced overproduction of collagenase may be a factor in the development of corneal ulcers, as well as other pathophysiological conditions such as cartilage destruction in arthritis. If so, inhibitors of this signal-transduction pathway may be useful as tools for further investigation and, eventually, as therapeutic agents to treat such disorders.

Animals↗

PubMed1993

Phase I clinical and pharmacology study of topotecan given daily for 5 consecutive days to patients with advanced solid tumors, with attempt at dose intensification using recombinant granulocyte colony-stimulating factor.

BACKGROUND: Topotecan has been shown in previous studies to be a specific inhibitor of topoisomerase I, a nuclear enzyme required for DNA replication and transcription. PURPOSE: Our objectives in this phase I clinical trial were to determine the maximum tolerated dose, dose-limiting toxic effects, and recommended phase II dose of topotecan and to define the pharmacokinetics of topotecan in humans. METHODS: Forty-three patients with advanced, incurable solid tumors were treated. Doses ranged from 0.5 to 2.0 mg/m2 daily for five days [corrected], with treatment cycles repeated initially every 28 days. Following the identification of the standard maximum tolerated dose, further dose escalations were attempted by following topotecan cycles with recombinant granulocyte colony-stimulating factor (rG-CSF). RESULTS: The maximum tolerated dose without rG-CSF for patients without prior cytotoxic therapy was 1.75 mg/m2 daily. The maximum tolerated dose for previously treated patients was 1.50 mg/m2 daily. The dose-limiting toxic effect was myelosuppression, with granulocytopenia being most commonly observed. Use of rG-CSF did not permit topotecan dose intensification, since thrombocytopenia and fatigue rapidly emerged as dose-limiting toxic effects. Plasma half-lives of topotecan (lactone form) were approximately 10 and 100 minutes for distribution and elimination phases, respectively. CONCLUSIONS: The doses of topotecan recommended for use in phase II clinical trials in solid tumors are 1.5 and 1.25 mg/m2 daily in previously untreated and previously treated patients, respectively. Based on observed rates of recovery from myelosuppression, treatment should be possible on a 21-day cycle. Dose intensification was not possible with the use of rG-CSF; however, rG-CSF may be a useful addition to the regimens of those few patients who experience either prolonged granulocytopenia or neutropenic sepsis or those who are not able to receive their second treatment cycle by day 21.

Adult↗

PubMed1993

Glycine effects on in vitro motor pattern generation in mouse spinal cord.

Bath applications of glycine typically inhibited electromyogram (EMG) activity in the gastrocnemius (G) and tibialis anterior (TA) muscles of neonatal mice, in vitro. Although rhythmic bursting occurred in response to glycine administration, cycle alternation between individual EMG bursts in G and TA muscles was not observed. That strychnine (a glycine 1 receptor antagonist) and cycloleucine (a glycine 2 receptor antagonist) could evoke motor rhythm, when given separately or in combination, confirms that glycine transmission is not required for motor pattern generation in mice. Strychnine application resulted in synchronized EMG bursting in G and TA muscles, suggesting that glycine 1 receptor activation does provide some reciprocal inhibition between the G and TA motor nuclei.

Animals↗

PubMed1993

Octreotide as an antineoplastic agent in the treatment of functional and nonfunctional neuroendocrine tumors.

BACKGROUND: Although patients with neuroendocrine tumors typically exhibit an indolent clinical course, the pace of disease accelerates and the prognosis deteriorates once objective progression of disease begins. Thirty-four patients with advanced neuroendocrine tumors were treated with octreotide as antineoplastic therapy. This treatment was begun only after documentation of clear objective progression of disease. METHODS: A Phase II trial was performed at a tertiary comprehensive cancer center. RESULTS: The median survival for this patient population from the start of octreotide therapy has not been reached, with a median follow-up of 29 months (range, 1-47 months). No major objective tumor regressions were seen. Seventeen patients (50%) experienced a computed tomography-documented stabilization of disease that was maintainable for a minimum of 2 months (median, 5 months; range, 0-27 months). Of the 34 patients, 20 patients received octreotide as their first antineoplastic therapy. The median survival for these 20 patients has not been reached, with a median follow-up also of 29 months (range, 12-41 months). CONCLUSIONS: Octreotide may influence the natural history of neuroendocrine tumors. The survival in patients treated with octreotide, as measured from the time of progression of disease, compares favorably with that of historical controls. Proof of a survival advantage for patients treated with octreotide would require a multicenter, randomized trial.

Adenoma, Islet Cell↗

PubMed1993

Endogenous ADP-ribosylation of glyceraldehyde-3-phosphate dehydrogenase that is not regulated by nitric oxide in Dictyostelium discoideum.

A 41,000 M(r) cytosolic protein (p41) in Dictyostelium discoideum was shown to be modified by ADP-ribosylation that was not regulated by nitric oxide (NO). This endogenous ADP-ribosylation was optimal at conditions distinct from those optimal for the NO-stimulated ADP-ribosylation of p41. These two activities were also differentially sensitive to reducing agents and modified different amino acids. The addition of haemoglobin, which sequesters NO, and of NO synthase inhibitors failed to block the endogenous ADP-ribosylation. P41 was purified to homogeneity. The N-terminal sequence of the purified protein was shown to be highly homologous to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Both endogenous and NO-stimulated activities ADP-ribosylated three isoforms of the protein, with pI values of 6.6, 6.8 and 7.0. In each case, the isoform with pI 6.8 was preferentially modified. Experiments using purified GAPDH indicate that both the endogenous and NO-stimulated ADP-ribosylation are self-catalysed modifications.

Adenosine Diphosphate↗

PubMed1993

Randomized trial of hepatic arterial floxuridine, mitomycin, and carmustine versus floxuridine alone in previously treated patients with liver metastases from colorectal cancer.

PURPOSE: This study was designed to determine if hepatic arterial therapy with floxuridine (F), mitomycin, and carmustine (BCNU) (FMB) is superior to hepatic arterial therapy with F alone in previously treated patients with hepatic metastases from colorectal cancer. PATIENTS AND METHODS: Ninety-five patients were randomized to intrahepatic FMB versus intrahepatic F. All patients had tumor progression after systemic chemotherapy (either therapeutic or adjuvant). RESULTS: There was no significant difference in response rate (47% FMB v 33% F; P = .17). Median survival was similar in the two groups, 19.1 months for the FMB group compared with 14.0 months for the F group (P = .23). The overall median survival was 16.8 months. In patients who received prior adjuvant therapy, there was no difference between the two groups, but response rate was high in both (50% FMB v 62% F). The response rate for all patients who had received only prior adjuvant therapy versus all those who had received prior therapy for metastatic disease was 57% and 35%, respectively (P = .066). In the subset of patients whose disease had progressed with prior systemic chemotherapy, the response rate to FMB was greater than that to F (47% v 23%; P = .035). CONCLUSION: The overall partial response rate of 39% and the overall survival of 16.8 months from initiation of intrahepatitis therapy show that hepatic arterial therapy is a reasonable treatment option for patients whose tumor does not respond to systemic therapy or whose disease progresses after adjuvant therapy for colorectal cancer.

Adult↗

PubMed1993

Effect of relative cumulative dose-intensity on survival of patients with urothelial cancer treated with M-VAC.

PURPOSE: To evaluate the received dose-intensity in a mature data set of patients with advanced urothelial cancer who received at least one cycle of the methotrexate (M), vinblastine (V), Adriamycin ([A], doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (C) regimen (M-VAC). PATIENTS AND METHODS: Received dose-intensity was evaluated over time by summing doses over cycles for each patient, cumulating treatment times, and assuming four cycles of chemotherapy were planned. Relative cumulative dose-intensity was then calculated for individual patients at the end of each cycle. To assess a relationship with survival, relative cumulative dose-intensity was then used as a time-dependent covariate in Cox regression. RESULTS: The median follow-up was 6 years and median survival 13.3 months, with 20 patients alive at the time of analysis. Out of a maximum of 1.0, the median relative dose-intensity for the M-VAC combination decreased from .69 to .59 from cycle 1 to cycle 4. Similarly, a decrease from .68 to .62 and from .80 to .72 was observed for A and C, respectively. The median received dose-intensity for A was 6.0 mg/m2/wk, and for C 14 mg/m2/wk. Neither the four-cycle relative cumulative dose-intensity for the M-VAC combination, nor the relative cumulative dose-intensities for A or C were found to be significant prognostic factors. CONCLUSION: The absence of an effect for received dose-intensity on survival may reflect the low dose-intensities of the components of the regimen actually delivered in this study. The results question whether the individual agents can be escalated sufficiently, with growth factor support, to improve significantly complete response proportions, a prerequisite for increasing the proportion of long-term survivors.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

Dose-intensification of MVAC with recombinant granulocyte colony-stimulating factor as initial therapy in advanced urothelial cancer.

PURPOSE: This study was undertaken to define an escalated dose schedule of methotrexate, vinblastine, doxorubicin, and cisplatin (E-MVAC) with hematopoietic growth-factor support, to define the ability to deliver E-MVAC with recombinant human granulocyte colony-stimulating factor (rhG-CSF) on 21- and 14-day schedules, and to assess the ability of rhG-CSF to maintain dose-intensity over four cycles of chemotherapy. PATIENTS AND METHODS: Twenty-three patients with transitional-cell carcinoma of the urothelium received E-MVAC in a phase I investigation. Patients were treated on an every-21-day (n = 19) or every-14-day schedule of administration (n = 4), with rhG-CSF support. Delivered dose-intensity was calculated at the completion of four cycles of therapy relative to the planned administration of conventional MVAC (relative dose-intensity [RDI]). Peripheral-blood progenitor cell kinetics in these patients were studied prospectively. RESULTS: Overall, the delivered RDI was 33% higher than the previously reported delivered dose-intensity of MVAC without hematopoietic support (140% for doxorubicin, 51% for cisplatin). Dose-intensity was well maintained through three cycles of therapy, after which leukopenia and thrombocytopenia became dose-limiting. Sixty-nine percent of patients with measurable disease responded, four (25%) with complete remissions. In five patients treated beyond the maximally tolerated dose (MTD), a 50- to 200-fold increase in G-CSF, granulocyte-macrophage CSF (GM-CSF), and interleukin-3 (IL-3)-responsive peripheral-blood progenitor cells over baseline was observed after 9 days of rhG-CSF administration. CONCLUSION: These findings demonstrate the feasibility and limitations of dose intensification of M-VAC with rhG-CSF. While the overall impact of the increased drug administration can only be assessed in randomized comparisons, the results of the present trial suggest that escalations of the components of the four-drug regimen are unlikely to improve significantly the outcome for patients with advanced urothelial tract tumors.

Adolescent↗

PubMed1993

[Clinical studies in three cases of pulmonary cryptococcosis].

We report three cases of pulmonary cryptococcosis in which one community acquired and two nosocomial infections were suspected. Clinical studies were focused on histological and immunological diagnosis and antifungal chemotherapy. The first case was initially suspected of having primary cryptococcosis. The second case was first suspected to have BOOP on the basis of clinical and radiological findings. The third was initially suspected of having lung cancer because of an enlarging mass lesion in fibrotic lung and elevated tumor markers. All cases were treated with antifungal agents. Two cases were treated with fluconazole alone, the other case with fluconazole and 5-fluorocytosine. In all cases, the abnormal shadows on chest X-ray demonstrated 50 to 90 percent improvement within 6 months, and cryptococcal antigen in the serum decreased. There were no side effects from the drugs.

Adult↗

PubMed1993

A fundus photographic method with narrow spectral band luminance.

We perfected the narrow spectral band fundus photographic system using interference filters at the wavelengths of 417, 478, 500, 530, 547, 570, 589, 607, 628 and 648 nm. Tests about the light penetration of filters and exposure of various brand films were made on this system. Studies of the contrast of fundal tissues and structures under the different narrow spectral band light were made on 43 Chinese fellow eyes. The results indicates that the interference filters of 570 nm have the highest light penetration. Kodak and Gongyuan films (make in China) are the optimal ones. Narrow spectral band fundus photography can eliminate the chromatic aberration and therefore improve the documentation of fundal details, enhance the contrast of pictures as compared with routine white light fundus photography.

Chromosome Aberrations↗

PubMed1993

[Two cases of pulmonary lymphangioleiomyomatosis].

We report two cases of pulmonary lymphangioleiomyomatosis with recurrent spontaneous pneumothorax. The cases were diagnosed by open lung biopsy. Case 1 was a 38-year-old woman, whose chest X-ray showed linear and reticular shadows. Lung tissue was negative for hormone receptors. She was treated with tamoxifen, but developed allergic symptoms. Her condition gradually deteriorated despite oxygen and progesterone therapy. Case 2 was a 41-year-old woman, whose chest X-ray showed a reticular shadows and slight overinflation. Hormone receptors were not examined, but the disease did not progress with oxygen, progesterone and GnRH agonist (Sprecur) therapy.

Adult↗

PubMed1993

[A case of intrapulmonary lymph node with silicotic nodules in a patient with idiopathic interstitial pneumonia].

A 61-year-old man was admitted to our hospital on October 8, 1991 because of abnormal shadows on chest X-ray at annual checkup at his company. Chest X-ray and CT on admission showed diffuse reticular shadows in bilateral lower lung fields and a nodular opacity approximately 10 mm in diameter in the right lower lung. Since transbronchial lung biopsy was not diagnostic, an open lung biopsy was performed on October 28, 1991. The lung specimens showed diffuse pulmonary fibrosis compatible with usual interstitial pneumonia and an intrapulmonary lymph node containing silicotic nodules. Only 29 cases (including the present case) of intrapulmonary lymph nodes have been reported. Although the causes of intrapulmonary lymph nodes are not clear, smoking is considered to play an important role in the development of pulmonary lymphoid tissue. In our case, the intrapulmonary lymph node contained silicotic nodules. Only several case have been reported to have silicotic nodules in the lymph nodes. As suggested by Kradin, they may be induced by relatively low levels of exposure to dust. Our case also had pulmonary fibrosis (IIP), and is the first reported case of intrapulmonary lymph node associated with IIP. Although it is difficult to determine these two diseases occurred coincidently or not, it is possible that a low level of dust exposure may have contributed to both silicotic nodules in the lymph node and IIP.

Adult↗

PubMed1992

Nitric oxide-releasing compounds inhibit Dictyostelium discoideum aggregation without altering cGMP production.

The effects of nitric oxide-releasing compounds on Dictyostelium discoideum cell development and guanylyl cyclase activity were studied. The addition of SNP (sodium nitroprusside) or SIN-1 (3-morpholino-syndnonimine) to starved cells inhibited their differentiation and aggregation in a concentration-dependent manner. In contrast to mammalian systems, SNP did not significantly affect guanylyl cyclase activity in cell lysates of D. discoideum, nor did it stimulate cGMP production in intact cells. The results suggest that the inhibitory effects of NO on D. discoideum cell aggregation are through a mechanism independent of an effect on guanylyl cyclase activity.

Animals↗

PubMed1992

Comparison of spontaneous motor pattern generation in non-hemisected and hemisected mouse spinal cord.

Spontaneous electromyogram (EMG) patterns in the gastrocnemius (G) and tibialis anterior (TA) muscles of spinal cord-hindlimb explants from neonatal mice were investigated. Compared to non-hemisected explants, neither longitudinal hemisection of the spinal cord nor hemisection plus transection at L1 significantly altered the incidence of spontaneous motor rhythm. Therefore, not only does each half of the neonatal spinal cord contain sufficient circuitry to generate motor rhythm, but the more reduced preparations were just as likely to produce such activity. Hemisected preparations, however, exhibited slower rhythm, perhaps due to the loss of excitatory commissural connections. No correlation was found between the number of cycles in a rhythmic sequence and cycle period. In hemisected as well as non-hemisected explants, sequences of spontaneous EMG rhythm occurred in either the G or TA muscle, but not in both muscles simultaneously. Consequently, cycle-to-cycle alternation between rhythmic bursting in the G and TA muscles was not observed. The excitability in such preparations was apparently insufficient for maintained activations of both muscles (either for cycle-to-cycle alternation or for co-contraction).

Animals↗

PubMed1992

Nitric oxide stimulates the ADP-ribosylation of a 41-kDa cytosolic protein in Dictyostelium discoideum.

Nitric oxide-releasing compounds were shown to activate an ADP-ribosyltransferase activity in the cytosol of Dictyostelium discoideum. The enzyme ADP-ribosylated a cytosolic protein of approximately 41 kDa, p41. Neither cGMP nor GTP and its analogues affected this ADP-ribosylation. p41 differs from other substrates ADP-ribosylated by cholera, pertussis, or diphtheria toxins. Treatment of ADP-ribosylated p41 with snake venom phosphodiesterase released adenosine 5'-monophosphate, indicating a mono-ADP-ribose-protein linkage. This linkage was stable to neutral hydroxylamine but was sensitive to mercury ions and iodomethane, suggesting an attachment to a cysteine residue. Treatment of intact cells with nitric oxide-releasing compounds appeared to stimulate the ADP-ribosylation of p41 and this modification was reversible.

ADP Ribose Transferases↗

PubMed1992

Guinea pig model of immunologic asthma induced by inhalation of trimellitic anhydride.

We established a model of asthma induced by trimellitic anhydride (TMA) in guinea pigs and assessed the role of sensitization in the development of their bronchial hyperresponsiveness, and relationship between bronchial responsiveness and bronchial inflammation. Fourteen guinea pigs (sensitized group) were administered 1 mg/0.5 ml of trimellity 36-bovine serum albumin intramuscularly and 0.5 ml of complete Freund adjuvant on Day 1 as the priming dose. Booster doses were repeated on Day 15. By Day 28, all of the sensitized animals showed a high passive hemagglutination titer against trimellityl 14-ovalbumin. On Day 29, they were challenged by an inhalation of TMA (150 mg/m3) for 30 min, and respiratory resistance (Rrs) was monitored by the oscillation method. In all sensitized animals, Rrs increased immediately upon challenge and returned to baseline within 6 h. The bronchial reactivity to acetylcholine (Ach), measured 6 h after TMA challenge in the sensitized animals, increased significantly (p < 0.01) compared with that measured 24 h before challenge; that measured 24 h later was not different from that before challenge. There was also a significant difference (p < 0.01) in the number of eosinophils in the lamina propria and the epithelium 6 and 24 h after the challenge inhalation in the sensitized group. The increased airway responsiveness to Ach in the sensitized animals was correlated with an increase in the number of eosinophils in the lamina propria and the epithelium. These observations suggest that humoral antibody and eosinophils are involved in the pathogenesis of TMA-induced asthma.

Acetylcholine↗