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Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 1,261 records · Page 70Linked to original sources
PubMed1996

Long-term secretion of therapeutic proteins from genetically modified skeletal muscles.

Protein delivery from genetically modified skeletal muscle has been reported previously. However, a stable and prolonged secretion was obtained in immunocompromised or newborn animals only. To evaluate the clinical relevance of this approach, we have transduced myoblasts from an adult beta-glucuronidase-deficient (MPS VII) mouse with retroviral vectors carrying either the human beta-glucuronidase cDNA or the murine erythropoietin (Epo) cDNA. The cells were then grafted into the tibialis anterior muscle of adult immunocompetent MPS VII recipients. Protein expression was controlled either by ubiquitous or muscle-specific transcriptional regulatory elements. Animals were analyzed over an 8-month period. The in situ detection of beta-glucuronidase activity revealed up to 60% of genetically modified myofibers in the recipient muscles. The human desmin promoter and enhancer showed the highest in vivo expression. Secretion of beta-glucuronidase induced a disappearance of lysosomal storage lesions in the liver and spleen of recipient animals. Delivery of Epo led to a permanent increase of hematocrit values over 3 months. These results showed that the transplantation of genetically modified myoblasts allowed a sustained secretion of recombinant proteins at therapeutic levels in immunocompetent adult mice. They suggest that the approach may be considered for human applications.

Animals↗
PubMed1996

Effects of National Cholesterol Education Program Step 2 diets relatively high or relatively low in fish-derived fatty acids on plasma lipoproteins in middle-aged and elderly subjects.

The effects of two National Cholesterol Education Program (NCEP) Step 2 diets (< or = 30% of energy as total fat, < 7% of energy as saturated fat, and < 200 mg cholesterol/d), one relatively high and the other relatively low in fish-derived fatty acids, on plasma lipoprotein concentrations and blood pressure were compared in 22 men and women with a mean (+/- SD) age of 63 +/- 10 y. Subjects were placed on a baseline diet similar to the diet currently consumed in the United States (35% of energy as total fat, 14% of energy as saturated fat, 35 mg cholesterol/MJ) for 6 wk and then on either an NCEP Step 2 diet relatively high in fish (Step 2 high-fish, n = 11) or relatively low in fish (Step 2 low-fish, n = 11) for 24 wk. All food and drinks were provided. Compared with baseline values, consumption of both the Step 2 high-fish and the Step 2 low-fish diets under weight-stable conditions was associated with significant decreases in plasma concentrations of total cholesterol (-14% and -19%, respectively), low-density-lipoprotein (LDL) cholesterol (-15% and -20%, respectively), and high-density-lipoprotein (HDL) cholesterol (-11% and -17%, respectively). Postprandial, but not fasting, triacylglycerol concentrations were significantly reduced during consumption of the Step 2 high-fish diet. There were no significant changes in these indexes after consumption of the Step 2 low-fish diet compared with the baseline diet. LDL particle size decreased significantly (-12%) only in subjects on the Step 2 low-fish diet. Both Step 2 diets caused small but significant reductions in diastolic blood pressure. Our results indicate that NCEP Step 2 diets relatively high or relatively low in fish are both effective in significantly reducing total and LDL-cholesterol concentrations without changes in the ratio of total cholesterol to HDL cholesterol under controlled weight-stable conditions in middle-aged and elderly subjects. A beneficial effect on diastolic blood pressure was also observed.

Aged↗
PubMed1996

An online immunoassay for LSD: comparison with GC-MS and the Abuscreen RIA.

A homogenous microparticle-based immunoassay has been developed for the detection of d-lysergic acid diethylamide (LSD) in human urine using the Online technology. This immunoassay is based on the principle of the kinetic interaction of microparticles in a solution where the drug content of the urine is directly proportional to the inhibition of the microparticle aggregation. Antibodies to LSD were obtained by immunizing goats with an LSD analogue derivatized through the indole nitrogen and conjugated to bovine thyroglobulin. The assay cutoff is 0.5 ng/mL LSD, and the clinical sensitivity for the detection of LSD and its metabolites in human urine samples is equivalent to the LSD Abuscreen RIA. Thirty-one samples previously screened LSD positive by Abuscreen RIA and confirmed by gas chromatography-mass spectrometry were analyzed by the Abuscreen OnLine LSD and Abuscreen LSD RIA assays. All thirty-one samples screened positive in the Abuscreen OnLine and Abuscreen RIA. OnLine's cross-reactivity to nor-LSD is greater than thirty-five percent; other structurally related compounds have similar cross-reactivity to that of the Abuscreen RIA. One thousand presumed negative urine samples were also analyzed; 992 (99.2%) of these gave negative results. The eight OnLine positive samples from this set were found to be negative by Abuscreen RIA. Typical qualitative within-run precision on the Hitachi 717 (at x = cutoff of 0.5 ng/mL; 0.5x, 1.0x, and 1.5x) was found to be less than 2.5%. Between-run precision was less than 3.0%.

Animals↗
PubMed1996

Risk factors for intravenous drug use and sharing equipment among young male drug users in Longchuan County, south-west China.

OBJECTIVES: To identify the risk factors for intravenous drug use and sharing of equipment in Longchuan County in south-west China. METHODS: Demographic information and sexual and drug-use-related behavior between 1 January 1991 and 1 August 1994 were collected retrospectively from a cohort of young male drug users aged 18-29 years in 82 villages. RESULTS: A total of 433 drug users were identified. The cumulative incidence of intravenous drug use was 40.0% during the 3.7-year study period. The annual incidence increased from 10% in 1991 to over 30% in 1994. Risk factors for intravenous drug use among drug users, according to the multivariate model, included having had premarital/extramarital sex [odds ratio (OR), 1.5; 95% confidence interval (CI), 1.01-2.3], having a family member who used drugs in 1991 (OR, 1.8; 95% CI, 1.1-2.9), and currently not married (OR, 1.6; 95% CI, 0.98-2.7). Being Buddhist protected against intravenous drug use (OR, 0.4; 95% CI, 0.2-0.9). The population attributable fraction was 30% for not being currently married, 17% for having had premarital/extramarital sex and 14% for having a family member who used drugs. The risk factor for sharing of equipment was being of Jingpo ethnicity (OR, 5.8; 95% CI, 2.5-13.8). The average incidence of sharing equipment was 19.6% per year. The population attributable fraction for sharing equipment was 58.5% for being Jingpo. CONCLUSIONS: The incidence of intravenous drug use and sharing equipment is increasing. Therefore, it is urgent that vigorous, effective intervention programs be initiated in southern Yunnan. Unmarried, sexually promiscuous Jingpo drug users with a family history of drug use should be especially targeted. Given the problems of transport and communication in this remote area of China, intervention programs which use existing social, governmental and community networks should be implemented.

Adolescent↗
PubMed1996

Interactions of nonpeptide angiotensin II receptor antagonists at imidazoline/guanidinium receptor sites in rat forebrain.

Imidazoline/guanidinium receptive sites (IGRS) are shown to be present in the subfornical organ and hypothalamic arcuate nucleus by a derivative of cirazoline, 2-(3-amino-4-[125I]iodophenoxy)methylimidazoline ([125I]AMIPI). Because many of the nonpeptide angiotensin II (Ang II) receptor antagonists contain imidazole ring structures, they may interact with IGRS. Therefore, we studied competitive activity of Ang II and several nonpeptide Ang II receptor antagonists [DuP 753 (losartan), EXP 3174, CV11974, and PD123319] at IGRS in rat forebrain. The results showed specific binding of 944 +/- 169 fmol/mg protein in the subfornical organ (n = 11) and of 367 +/- 27 fmol/mg protein in the arcuate nucleus (n = 6) at 0.4 nM [125I]AMIPI, as defined by competition with 10 microM cirazoline. Specific [125I]AMIPI binding was competed for completely by 10 microM idazoxan or clonidine as further characterization of IGRS. Ang II and the nonpeptide AT1 and AT2 antagonists did not significantly compete for specific [125I]AMIPI binding in either brain region at concentrations of 10 microM (< 20% competition with each compound), which is 10- to 100-fold higher than the concentration necessary to compete completely for their respective Ang II receptor subtypes. Only at the highest concentration (100 microM) did losartan compete significantly for binding (56 +/- 8%). Therefore, Ang II receptor antagonists interact with IGRS in rat forebrain cardiovascular areas only at high concentrations.

Angiotensin II↗
PubMed1996

Experimental study on reinnervation of vocal cord adductors with the ansa cervicalis.

The purpose of this study was to reestablish the adduction of the paralyzed vocal cord through reinnervation of the adductor muscles for unilateral vocal cord paralysis. In nine dogs, the adductor branch of the recurrent laryngeal nerve was anastomosed to the main branch of the ansa cervicalis. Six months later, various techniques of observation showed that seven of nine cases had excellent to good adduction during whining. Adduction was caused by reinnervation of the adductor muscles from the ansa cervicalis as demonstrated by laryngeal spontaneous and evoked electromyography, contraction tension, and various histologic findings. Therefore, the new technique could be a good treatment of unilateral vocal cord paralysis.

Animals↗
PubMed1996

Update: laryngeal reinnervation for unilateral vocal cord paralysis with the ansa cervicalis.

Eight patients underwent ansa cervicalis anastomosis to the adductor branch of the recurrent laryngeal nerve for unilateral vocal cord paralysis. They were followed long enough (at least 1 year) to determine if the procedure was successful. All cases have been subjected to preoperative and postoperative voice recording, acoustic analysis, and videolaryngoscopy. Some of them have been subjected to stroboscopy and electromyography (EMG). Data from these cases indicate that satisfactory phonatory quality may be achieved after the procedure. The reinnervated vocal cord neither abducted nor adducted, but it presented itself in midline for precise apposition with the normal cord. Synchronous mucosal waves in both vocal cords could be observed. EMG showed that the procedure produced satisfactory reinnervation of the adductory muscles. Therefore, the authors believe that the procedure could be proposed as an alternative to Teflon injection or thyroplasty in selected cases.

Adult↗
PubMed1996

Genome segment 5 of rice ragged stunt virus encodes a virion protein.

The complete nucleotide sequence of the genome segment 5 (S5) of a Thai isolate of rice ragged stunt virus (RRSV) was determined. The 2682 nucleotide sequence contains a single long open reading frame capable of encoding a polypeptide with a molecular mass of approximately 91 kDa. Polypeptides encoded by various truncated cDNAs of S5 were expressed using the pGEX fusion protein vector and the highest level of fusion protein was obtained from a construct encoding a hydrophilic region of S5 protein. Antibodies raised against this fusion protein recognized a minor polypeptide, with a molecular mass of approximately 91 kDa, that was present in purified preparations of RRSV particles, infected insect vectors and infected rice plants. This indicates that RRSV S5 encodes a minor structural protein. Comparing the RRSV S5 sequence with sequences of other reoviruses did not reveal any significant sequence similarities.

Amino Acid Sequence↗
PubMed1996

Sequence specificity for DNA binding by Escherichia coli SoxS and Rob proteins.

SoxS is a transcriptional activator of oxidative stress genes in Escherichia coli. SoxS in vitro binds the promoters of soxRS-regulated genes such as micF, zwf, nfo and sodA, forms multiple protein-DNA complexes, and recruits RNA polymerase to the promoters. E. coli Rob protein, with an N-terminus 55% identical to SoxS, was initially identified by its binding to the oriC replication origin, but Rob in vitro binds some of the same promoters as SoxS and in vivo activates some SoxS-regulated genes. In this work we show that the multiple complexes with SoxS arise from the presence at least two independent binding sites in each of the ++offcF and zwf promoters. SoxS and Rob each form only a single complex with a 20 bp DNA oligonucleotide corresponding to the region immediately upstream of the -35 element of the micF promoter. Methylation interference identified several conserved purine residues required for binding to micF and five other SoxS-binding sites. Together with binding studies using mutated ollgonucleotides and published DNase I footprinting data, this information was used to form a consensus for SoxS sequence specificity: AN2GCAYN7CWA (where N is any base, Y is a pyrimidine, and W is A or T). The sequence requirements for Rob binding differed somewhat from those of SoxS. Using the SoxS-binding consensus, several genes potentially regulated by soxRS were identified in an E. coli genomic database; some of these genes have functions that might contribute to cellular resistance to oxidative stress.

Bacterial Proteins↗
PubMed1996

A comparison by payor/provider type of the cost of dying among frail older adults.

OBJECTIVE: To compare expenditures and healthcare service use between decedents (in their last year of life) and survivors, all of whom were frail older people, under three payor/provider types. DESIGN: In-home interviews were conducted by home care nurses at baseline and at 6-month intervals for an 18-month period. Utilization and cost data were collected directly from providers and the Health Care Financing Administration for 12 months immediately before death for decedents and for the first 12 months of follow-up for survivors. SAMPLE: Five hundred seventy-seven frail older patients of an integrated healthcare system who were receiving physician prescribed home health services, under Medicare fee-for-service (FFS), Medicare HMO, or Medicare-Medicaid coverage. Frailty was defined as the receipt of physician-prescribed home healthcare services. OUTCOME MEASURES: Acute and long-term healthcare service utilization and expenditures; total healthcare expenditures. RESULTS: After controlling for baseline differences, significant differences in utilization and expenditures of survivors (n = 450) and decedents (n = 127) were demonstrated. Compared with survivors, frail older decedents were approximately: 7 times as likely to have had any hospital admissions 3 times as likely to have had one or more emergency room visits 8 times as likely to have 30 or more physician visits 4 times as likely to have been admitted to a skilled nursing facility and twice as likely to have used home health services after the baseline episode. On average, total expenditures for decedents were 276% higher than for survivors. Total expenditures for Medicaid-Medicare beneficiaries were 42% higher than expenditures for FFS participants, primarily because of higher hospitalization and emergency room expenditures. There were no differences in utilization and expenditures between HMO enrollees and FFS beneficiaries. Finally, interactions between decedent status and payor/provider were not statistically significant in multivariate analyses. CONCLUSION: During the last year of life, frail older people exhibit the same pattern of higher expenditures and service utilization as the general Medicare population. However, differences between decedents' and survivors' healthcare expenditures and resource use did not vary by payor/provider. Thus, cost-containment strategies should focus on new forms of managing healthcare services beyond those currently practiced within Medicare HMOs, traditional FFS, or Medicare-Medicaid in California.

Aged↗
PubMed1996

Initial characterization of viral sequences from a SHIV-inoculated pig-tailed macaque that developed AIDS.

In this study, we report on the derivation of a pathogenic SIV-HIV chimeric virus (SHIV) and the initial characterization of the viral sequences from the first (macaque PPc) of a series of pig-tailed macaques that developed CD4+ T cell loss and AIDS. Viral genes were amplified by PCR from the brain, lymphoid, and kidney tissues and their sequences compared to the original SHIV used to initiate passages in macaques. Our results show that the vpu gene, which was nonfunctional in the original SHIV, now coded for functional protein in macaque PPc. The tat and rev genes had no consensus changes but the nef gene had 4-5 consensus changes, depending on the tissue examined. The gp 120 gene had the highest number of nucleotide and amino acid substitution rates that varied from 0.64% to 1.44% and 1.17% to 3.71%, respectively, again depending on the tissue examined. These results suggest that a constellation of changes accumulated at the genomic level during the derivation of a SHIV that was pathogenic for pig-tailed macaques.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Verification of milled two-dimensional photon compensating filters using an electronic portal imaging device.

A computer-driven milling machine is being installed at the Mallinckrodt Institute of Radiology to fabricate photon compensating filters for conventional compensation and beam-intensity modulation. Commissioning and quality assurance procedures are being developed for the design, fabrication, and delivery systems prior to using the milled filters in the clinic. The portion of the quality assurance procedures governing the filter fabrication using a computer-driven milling machine includes, in part, a comparison of designed and fabricated filters. Test filters include geometrically regular filters, such as flat surfaces and steps. The verification of these shapes is accomplished using spatial measurements. However, to test the mill's ability to generate complex curved surfaces, filters with more complicated surfaces are generated. These filters do not lend themselves to precise verification using physical measurement of the thickness distribution. A method has been developed to verify the thickness distributions of these complex filters by irradiating the filters with high-energy x rays and comparing the scattered and transmitted fluence to the fluence calculated using the intended filter shape. The fluence measurement is made using a calibrated commercial liquid ionization chamber electronic portal imaging device. The calculated fluence is separated into transmitted primary and scattered fluences and is determined using a convolution of a distributed radiation source kernel with an exponential filter attenuation function. The attenuation coefficient is measured for the filter material (Lipowitz metal) and fit to a second-order polynomial in filter thickness and off-axis distance. The distributed source kernel is measured using a split-field technique and fit to a sum of three two-dimensional Gaussian distributions. The scattered radiation is modeled by the Klein-Nishina cross section. The algorithm is tested by comparing calculated fluences with measured fluences for a series of machined filters: an open field, flat filters of 9.6-, 15.8-, and 31.6-mm thickness, split-field filters, and a pyramid-shaped filter. In each case, the algorithm calculates the fluence to within 3% of the measured values over the entire irradiated field size to within 1.5 cm of the collimated field edges.

Algorithms↗