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Biomedical subjects

Z Zhao

Publications and source records attributed to Z Zhao.

408 records · Page 23Linked to original sources

Stochastic cost-effectiveness analysis: a simultaneous marginal-effect approach.

OBJECTIVE: The purpose of this study is to develop a cost-effectiveness methodology in the context of a simultaneous modeling framework that provides consistent point and interval estimates. METHODS: A simultaneous model of cost and effectiveness functions was developed to measure the incremental cost-effectiveness ratio for competing medical interventions. A feasible nonlinear least-squares method was suggested to estimate the simultaneous model. Using a series of hypothetical data, a simulation analysis was performed to show the superior performance of the proposed model, relative to the average-effect model, a widely used approach to cost-effectiveness estimation. RESULTS: The traditional average-effect approach has two shortcomings. First, it assumes two strong conditions: truly random distributions of all the significant nontreatment variables (both observed and unobserved) across study groups, and the independence of cost and effectiveness variables. Second, it does not give the confidence interval, an important measure to assess the stochastic nature and robustness of point estimates. In contrast, the simultaneous modeling approach provides marginal-effect estimates, imposing no restrictions on the random distributions of the individual characteristics across study groups. Furthermore, it takes into account the simultaneity of cost and effectiveness functions being estimated. The simulation analysis showed that the simultaneous modeling approach is significantly more unbiased and efficient in predicting the true cost-effectiveness ratio. CONCLUSION: The simultaneous modeling approach is superior to the average-effect approach in the estimation of incremental cost-effectiveness ratios using data with significant nontreatment confounding factors. The advantages of the simultaneous modeling approach are particularly appealing for evaluative studies dealing with large-scale retrospective data at the patient level.

Journal Article↗

The design and synthesis of purine inhibitors of CDK2. III.

Cyclin-dependent kinases (CDKs) belong to a class of enzymes that control the ability of a cell to enter into and proceed through the cell division cycle. Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects.

Adenine↗

Lymphatic hyaluronan flux from skin increases during increased lymph flow induced by intravenous saline loading.

Hyaluronan is a structural component of the interstitial matrix in skin and is catabolized locally in skin as well as by lymphatic removal and subsequent degradation in lymph nodes and liver. The present experiments were designed to evaluate the role of interstitial fluid flux in turnover of hyaluronan in skin by measuring the maximal lymphatic flux of hyaluronan. Lymph flow, total protein concentration, hyaluronan concentration, and flux were measured every 15 min in prenodal lymph from the hind paw in 12 pentobarbital-anesthetized mongrel dogs at normal and increased interstitial fluid flux. An intravenous saline load (15% of body weight during the course of 30 min) was followed by a one-step increase in local venous pressure 30 min later (to a maximum of 50 mm Hg) and maintained at this level for the next 240 min. Lymph flow and hyaluronan concentration during the control period averaged 25.6 +/- (SD) 23.2 (range 4.7-61.9) microliters/min and 8.6 +/- 2.8 (range 2.0-11.6) micrograms/ml, respectively. The hyaluronan concentration fell by 30% during the experimental period, while the lymph flow increased up to ten times above control. Total tissue water increased from 1.73 +/- 0.11 ml/g dry weight during the control period to 1.91 +/- 0.12 ml/g dry weight at the end of the experiment (p < 0.01). The corresponding tissue contents of hyaluronan averaged 3.5 +/- 0.9 and 3.6 +/- 0.6 mg/g dry weight, respectively (p > 0.05). The average lymphatic hyaluronan flux was 8.4 +/- 5.4 micrograms/h during the control period, peaked at about 60 micrograms/h, and averaged 33.6 +/- 13.9 micrograms/h during the last hour of the experimental period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Exposure limits for ultra-short wave radiation in work environments.

Exposure limit values for ultra-short wave radiation of humans were derived on the basis of epidemiological survey and experimental exposure of rabbits. Eighteen male rabbits were divided into 4 groups randomly. Three groups were irradiated with ultra-short waves (100 MHz) at 35, 1.5-3.5, and 0.07 mW/cm2 power density in an E-polarized TEM Cell at 24 +/- 4 degrees C ambient temperature. The last group in a sham chamber served as controls. Irradiation was performed 3 hours per day, 5 days per week for 24 weeks. Thermal effects occurred in the group irradiated at 35 mW/cm2. The thermal threshold limit value was set at 1.5 mW/cm2. An epidemiological survey was carried out on 136 factory workers and TV operators exposed over one year to ultra-short wave radiation at 0.2 mW/cm2. They were compared with 108 controls. The only complaint of the exposed group was neurosis. The exposure limit value (ELV) to short wave radiation was set at 0.2 mW/cm2 by using a 15- and 20-fold safety factor.

Animals↗

Experimental studies of pancreatic transplantation after freezing and thawing.

The successful rat pancreatic transplantation, after 30 minutes cryopreservation at -80 degrees C, is presented with the normal graft function till the 6th postoperative day maximum. The freezing device used by the authors is shortly described. The choice of optimal freezing and thawing parameters is discussed. Organ freezing is a hopeful method which could serve to preserve the solid organs for a long period of time. Our former experimental research showed that slow freezing (1-2 degrees C/min) and fast thawing (> 100 degrees C/min) had produced less damage to the pancreas of the rat [1]. Recently we performed rat pancreatic transplantation after freezing and thawing the donor pancreas with the parameters mentioned above.

Animals↗

Solid-phase synthesis of extended lactam ring systems: preparation of amino acid alpha-fluorenylmethyl esters for the synthesis of reverse-extended lactams.

Conventional side-chain to side-chain cyclization between Lys/Orn and Asp/Glu side chains has the inherent shortcoming of limited variability in the ring sizes; limited by the amino acids involved in the lactamization. A novel approach to modulate the ring size has been introduced by using "spacers" (e.g., Gly, beta-Ala, gamma-Aba). General solid-phase procedures were developed that enabled the insertion of these spacers for the preparation of extended and reverse-extended lactam ring systems. Extended lactam ring systems were prepared using the Boc/Bzl strategy with Fmoc protection on the side chain of the basic residue, Lys/Orn. The spacer was introduced as the Fmoc amino acid, and chain elongation proceeded by the Boc/Bzl strategy. The acidic residue, Asp/Glu, involved in the lactam bridge was introduced with side-chain -OFm protection. Selective deprotection of the Fmoc and -OFm functions was followed by BOP cyclization, further chain elongation and HF cleavage. Reverse-extended lactam ring systems were prepared analogously using the Boc/Bzl strategy with the initial introduction of -OFm protection on the side chain of the acidic residue. In this case, amino acid alpha-fluorenylmethyl esters were used as the spacers. Amino acid alpha-fluorenylmethyl ester hydrochlorides were prepared in two steps from N-t-butyloxycarbonyl amino acids in excellent yield. These intermediates have general utility in peptide synthesis, including their specific application as "spacers" for the solid-phase synthesis of extended cyclic peptides (lactams). Using these intermediates, we prepared a model dicyclo-peptide that contains both an extended and reverse-extended lactam ring system.

Amino Acid Sequence↗

The effects of radiofrequency (< 30 MHz) radiation in humans.

121 workers who were exposed to RFR (< 30 MHz) over one year were examined. They were divided into two groups: one group was exposed to high electric field intensity (> or = 100 V/m), another to low intensity (< 100 V/m) and both groups were compared to control subjects. No significant changes in the functioning of the autonomic nervous system and blood parameters (Hb, WBC and blood platelets) occurred in the exposed subjects of either group. Some changes in ECG (ST-T interval and abnormal heart rate) were observed in the group exposed to high intensity (> or = 100 V/m) radiation. 100 V/m is suggested as an exposure limit for RF (< 30 MHz) radiation.

Adult↗

Effects of N-(4-hydroxyphenyl)-retinamide on the number and cytotoxicity of natural killer cells in vitamin-A-sufficient and -deficient rats.

N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid with anticarcinogenic activity, has been shown to lower the plasma retinol level rapidly and significantly. We reported previously that vitamin A-deficient rats (plasma retinol < 0.175 mumol/l) have a low number of natural killer (NK) cells in peripheral blood. To investigate the effects of 4-HPR on NK cell number and activity, two studies were conducted. In study 1, vitamin-A-sufficient rats were fed a 'therapeutic' dose of 4-HPR (2 mmol/kg of diet) for 30 days. Despite a low plasma retinol concentration (approximately 0.1 mumol/l), the number of NK cells was not reduced. Moreover, the NK cytolytic activity per cell was significantly elevated. White blood cell and differential counts were normal. In study 2, the biological activity of 4-HPR was examined in vitamin-A-deficient rats. Rats depleted of vitamin A were fed a diet containing 4-HPR (54.7 micrograms/g of diet) for 11 days. Vitamin-A-dependent processes including growth, hematocrit, lymphocyte count and the number of NK cells were restored. For comparison, another group of vitamin-A-deficient rats were repleted with retinoic acid (RA; 4.2 micrograms/g diet); this treatment also effectively restored these vitamin-A-dependent processes. Therefore, despite the plasma-retinol-lowering property of 4-HPR, treatment with this retinoid did not impair NK cell number or function. Indeed, 4-HPR showed vitamin A activity similar to RA, and may stimulate NK cell cytotoxicity.

Animals↗

The role of vitamin A in natural killer cell cytotoxicity, number and activation in the rat.

The cause of low natural killer (NK) cell activity in vitamin-A-deficient rats was investigated in the current study. Cytotoxicity correlated with the percentage of NK cells (3.2.3-positive cells) in peripheral blood mononuclear cells (PBMC; r = 0.85) and spleen (r = 0.70). Lytic activity per NK cell did not differ between vitamin-A-deficient rats and controls in PBMC, whereas it did in spleen. Vitamin A deficiency did not impair the ability to produce interferon (IFN), increase lytic efficiency and expand the NK cell pool upon poly(I:C) stimulation in vivo. Nor was the in vitro activation by IFN-alpha/beta or interleukin-2 affected. Thus, vitamin A is essential for maintaining basal NK cell number and activity, but not for NK cell activation.

Animals↗

Effect of lipid extraction methods on total dietary fiber and nonstarch polysaccharide contents of selected nuts and seeds.

Three extraction methods were used to remove lipid materials from 8 edible nuts and seeds before analysis for their total dietary fiber (TDF) and nonstarch polysaccharide (NSP) contents. Portions of ground materials were extracted by: n-hexane, followed by 80% methanol, n-hexane-acetic acid (95 + 5, v/v), and supercritical carbon dioxide. Defatted samples were gelatinized in water and incubated with amyloglucosidase; 95% ethanol was added to the hydrolyzates, and the residues were collected on tared glass crucibles. TDF was calculated according to a simplified enzymatic-gravimetric method developed in our laboratory, and NSP was determined as described by Englyst and coworkers. Dietary fiber values obtained with any of the extraction methods range from 3.47 g/100 g for cashews to 28.56 g/100 g for sunflower seeds. Nonstarch polysaccharide values range from 2.43 g/100 g for pecans to 5.56 g/100 g for peanuts. With the exception of sunflower seeds, samples extracted with supercritical carbon dioxide had lower TDF contents but similar amounts of NSP compared with samples extracted by the other 2 methods.

Acetic Acid↗

Identification and characterization of radiation damaged products of monophosphate nucleosides by on-line capillary isotachophoresis-electrospray ionization mass spectrometry.

Analysis of trace levels of DNA damage as a biomarker of human exposure to radiation levels represents a significant challenge. Capillary isotachophoresis (CITP) is well suited for this application due to its high separation efficiency, large sample loading capacity, and relative ease of interfacing with highly specific and sensitive mass spectrometric detectors. This study describes the use of reversed anionic CITP coupled on-line with electrospray ionization-mass spectrometry (ESI-MS) for the identification and characterization of small quantities of radiation induced damage to deoxynucleotide monophosphates. CITP with ESI-tandem MS also provides structural information on the nature of the damage in addition to the molecular weight. This approach has the attraction of allowing the direct on-line determination of damaged nucleotides, as well as the free bases and nucleosides, and avoids the need for sample hydrolysis and/or derivatization.

Biomarkers↗