Proposal for a loophole-free test of the Bell inequalities.
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Biomedical subjects
Publications and source records attributed to S Li.
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Neuroanatomical data have clearly demonstrated the existence of synaptic contacts between neuropeptide Y (NPY) endings and tuberoinfundibular dopaminergic (TIDA) neurons in the rat arcuate nucleus. In order to determine the influence of NPY in the biosynthesis of dopamine, we have studied the effects of NPY and some NPY analogs on tyrosine hydroxylase (TH) gene expression in TIDA neurons in the male rat. The following peptides: NPY, PYY, [Leu31, Pro34]-NPY (a Y1 receptor agonist) and NPY13-36 (a Y2 receptor agonist) were injected into the left lateral ventricle of adult male rats. All the animals were perfused with 4% paraformaldehyde 4 h after injection. Cryostat sections through the arcuate nucleus were processed for quantitative in situ hybridization. The intracerebroventricular injection of NPY, PYY and [Leu31, Pro34]-NPY induced an increased of 43, 33 and 42%, respectively, in the number of grains overlying TH neurons. On the other hand, the Y2 receptor agonist NPY13-36 did not influence mRNA levels. These data then strongly suggest that NPY positively regulates the genetic expression of TH in rat TIDA neurons via the Y1 NPY receptor subtype.
Dose-surface histograms are studied and compared with dose-volume histograms, as an evaluation tool for prostate treatment planning. For thin walled hollow organs, such as the rectum and bladder, the surface area irradiated is a more appropriate measure of the biological effect than the full volume. It is also more accurate and efficient to define the surface for a hollow structure and compute the surface area histograms. Application of the dose-surface histograms provide new insights into prostate treatment planning. A simple idealized geometry model demonstrates that the percentage surface area intersected by the geometric beam edge differs from the percentage volume intersected. For a group of prostate patients, it is shown that the dose-surface histograms yield substantially different results from the dose-volume histograms in ranking four-, six-, and, eight-field treatment plans and in calculating the fraction of the rectum irradiated to high dose. The difference in terms of surface area between these plans in the high-dose region is usually less than that in terms of the volume, and a reverse of plan ranking order can consequently occur. The percentage of organ surface irradiated to high dose is typically greater than the percentage volume by 5% to 10%. The use of the dose-surface histograms in analysis of organ motion and/or patient setup uncertainty, and analysis of rectal complications, is also discussed.
The rat whey acidic protein (WAP) gene contains a mammary gland-specific and hormonally regulated DNase I-hypersensitive site 830 to 720 bp 5' to the site of transcription initiation. We have reported previously that nuclear factor I (NFI) binding at a palindromic site and binding at a half-site are the major DNA-protein interactions detected within this tissue-specific nuclease-hypersensitive region. We now show that point mutations introduced into these NFI-binding sites dramatically affect WAP gene expression in transgenic mice. Transgene expression was totally abrogated when the palindromic NFI site or both binding sites were mutated, suggesting that NFI is a key regulator of WAP gene expression. In addition, a recognition site for mammary gland factor (STAT5), which mediates prolactin induction of milk protein gene expression, was also identified immediately proximal to the NFI-binding sites. Mutation of this site reduced transgene expression by approximately 90% per gene copy, but did not alter tissue specificity. These results suggest that regulation of WAP gene expression is determined by the cooperative interactions among several enhancers that constitute a composite response element.
Mouse embryo cells expressing a wild-type number of insulin-like growth factor I receptors (IGF-IR) (W cells) can be transformed either by simian virus 40 large T antigen (SV40 T) or by overexpressed insulin receptor substrate 1 (IRS-1), singly transfected. Neither SV40 T antigen nor IRS-1, individually, can transform mouse embryo cells with a targeted disruption of the IGF-IR genes (R- cells). However, cotransfection of SV40 T antigen and IRS-1 does transform R- cells. In this study, using different antibodies and different cell lines, we found that SV40 T antigen and IRS-1 are coprecipitated from cell lysates in a specific fashion, regardless of whether the lysates are immunoprecipitated with an antibody to SV40 T antigen or an antibody to IRS-1. The same antibody to SV40 T antigen, however, fails to coprecipitate another substrate of IGF-IR, the transforming protein Shc, and two other signal-transducing molecules, Grb2 and Sos. Finally, an SV40 T antigen lacking the amino-terminal 250 amino acids fails to coprecipitate IRS-1 and also fails to transform R- cells overexpressing mouse IRS-1. These experiments indicate that IRS-1 associates with SV40 T antigen and that this association plays a critical role in the combined ability of these proteins to transform R- cells. This finding is discussed in light of the crucial role of the IGF-IR in the establishment and maintenance of the transformed phenotype.
A systematic review of the 2.1 mu holmium-YAG laser for gall stone lithotripsy was undertaken. This infrared laser, which can be used endoscopically and percutaneously, has safety advantages over other lasers and has potential as a general purpose vascular and surgical tool. Twenty nine gall stones (mean mass 1.3 g) were fragmented in vitro using pulse energies of 114 to 159 mJ/pulse at 5 Hz with a 0.6 mm fibre, while being held in an endoscopy basket. All stones were successfully fragmented, requiring an average of 566 pulses with a 5 Hz pulse repetition frequency. The number of pulses required increased with gall stone size and mass (p < 0.01), and decreased with both pulse energy (p < 0.01) and operator experience (p < 0.05). The biochemical content of the stone did not significantly affect the number of pulses needed. The potential hazard of the laser to the biliary endothelium was investigated. At the pulse energies used, five pulses at close contact penetrated into the serosa of fresh gall bladder wall. No damage was seen when two pulses were fired. This laser shows considerable promise in gall stone lithotripsy. Until further safety data are available, however, its use with endoscopic vision is advised.
Lipopolysaccharide (LPS) treatment impairs cardiac myocyte contractility in a nitric oxide synthase (NOS)-dependent manner. The objective of this study was to assess whether protein kinase C (PKC) transduces the LPS signal into an enhanced NOS activity in rat cardiac myocytes. LPS (100 ng/ml) stimulated myocyte PKC activity, inducible NOS (iNOS) expression, and NOS activity in a time- and protein synthesis-dependent fashion. Directly activating PKC with beta-phorbol 12,13-dibutyrate (beta-PDB) also induced myocyte iNOS synthesis and NOS activity and reduced electrically stimulated contractility, while the inactive alpha-PDB was ineffectual. Contractility could be restored to beta-PDB-incubated cells by superfusion with the NOS inhibitor N omega-nitro-L-arginine methyl ester. PKC blockade with sphingosine, chelerythrine, or calphostin-C precluded LPS- and beta-PDB-induced increases in NOS activity and protected contractility. Depletion of PKC by 18 h of incubation with beta-PDB in the presence of chelerythrine also blocked acquisition of enhanced NOS activity and contractile dysfunction when the myocytes were subsequently exposed to LPS. These findings suggest that PKC is a significant intracellular mediator for the effects of LPS on cardiac cell NOS activity and contractile function.
It is well known that the adrenal medulla contains high concentrations of neuropeptide Y (NPY) where it coexists with epinephrine and norepinephrine. In order to evaluate the possible involvement of NPY in the regulation of the chromafin cells of the rat adrenal medulla, we have studied the effects of NPY and some NPY analogs on the concentrations of tyrosine hydroxylase (TH) mRNA. The following peptides, NPY, PYY, [Leu31, Pro34]-NPY (a Y1 receptor agonist) and NPY13-36 (a Y2 receptor agonist) were administered intravenously at the dose of 40 micrograms/100 g body weight. All the animals were perfused with 4% paraformaldehyde 4 h after injection and cryostat sections of adrenals were processed for in situ hybridization using a 35S-labelled oligonucleotide probe encoding for rat TH. Optical density measurements performed in adrenal medulla demonstrated that the administration of NPY, PYY, and [Leu31, Pro34]-NPY induced a marked increase in the hybridization signal while the Y2 receptor agonist NPY13-36 did not affect TH mRNA levels. Then, these data clearly indicate that NPY positively regulates the genetic expression of TH probably via the Y1 NPY receptor subtype. They suggest that variations in the levels of circulating NPY or in the release of NPY by the chromaffin cells themselves (in autocrine and/or paracrine way) can increase the biosynthesis of catecholamines in rat adrenals.
Previously isolated human placental cDNA clones represent a fusion of specific RNA sequences encoded by two genes: lysosomal chitobiase (CTB) and G-protein gamma 5 subunit (GNG5, Fisher and Aronson, 1992a, 1992b). Both genes have now been mapped to 1p by PCR analysis of somatic cell hybrids and further refined to 1p22 by fluorescence in situ hybridization (FISH) using a YAC clone that contains both the chitobiase and gamma 5 genes.
In a national trend, large, acute-care hospitals located in urban areas of the nation were continuously broadening their service scope, adding services at the rate of one each year, from 1982 to 1987. This study proposes that the underlying rationale of hospital service-scope expansion is status-gap minimization. This perspective was quantitatively interpreted and tested by a dynamic modeling analysis. Findings support status-gap minimization as the rationale for service-scope expansion. Using multivariate regression and dynamic modeling analysis, the study demonstrates that the cross-sectional relationship between two steady states--the relationship between service scope and market share--is positive and statistically significant. However, the market share change is not related to hospital service scope. The interpretation offered is that hospitals expand the scope of services looking not so much to increase their market share benefit in the short run as to raise their organizational status. In the long run, higher organizational status such as broader service scope then benefits market share.
Pregnant Yorkshire gilts (n = 42) were fed caffeine (6 g/d) or served as controls from d 60 of pregnancy until d 4 postpartum to test the effect of caffeine on mammary gland development, milk yield, and feed consumption. Caffeine reduced voluntary feed intake (P = .001) and body weight gain (P = .001) of gilts from d 60 to 109 of gestation. Pig birth weight in the treated group was less than (P = .01) that in the control group. However, pig viability score at birth was not affected by maternal caffeine ingestion. For assessing mammary gland DNA, RNA, dry fat-free tissue (DFFT), fat, and protein content, four sows from the caffeine group and three controls were slaughtered on the 1st d of lactation. Immediately after slaughter, mammary systems were removed, separated by gland, and dissected free of skin, muscle, and fatty pad, which had not been invaded by glandular tissue. The DNA and RNA content were evaluated in DFFT. Caffeine increased mammary RNA content (P = .023) and milk yield (P = .001) on d 1 of lactation. However, DNA, DFFT, fat, and protein were not significantly increased, although values were somewhat greater in the treatment group (approximately 82%). On d 21 of lactation, milk yield of treated sows did not differ from that of controls. The increased milk yield on d 1 of lactation was due to increased mammary epithelial cell activity and cell numbers. These results indicate that caffeine feeding can have a positive effect on porcine mammary gland development as well as milk yield.
Nine patients exposed to gentamicin ototoxicity were tested with active head movements to determine their high-frequency (2-6 Hz) horizontal and vertical vestibulo-ocular reflex (VOR) responses. Results showed a common pattern documenting patients' reports of oscillopsia during walking: gains of 0.5 or less, and phases less than 180 degrees. A subset of these patients undergoing exercise rehabilitation therapy were tested repeatedly during follow-up visits to monitor changes in their VORs. VOR improvements toward reduced oscillopsia were correlated with patients' reported reduction of symptoms. Each patient's VOR changes over time were monitored with a quantitative least-squares method which predicted results of the next test, based on trends from three or more previous tests. The method was tested by comparing predicted results with actual test results, following the next test. Preliminary results show relatively accurate predictions up to 6 weeks in advance of actual tests, at least when trends of recent, previous tests were in a consistent direction. We conclude that predictive monitoring of changing VOR states can be useful for continuing, or modifying, the course of vestibular rehabilitation therapy, by providing quantitative prediction estimates of future results.
The human hepatocellular carcinoma was successfully heterotrasplanted into nude mice and 10 passages were made seriously during 11 months. Initial take rate was 14.3% and then the take rate increased to 100% after the 3rd passage. Histological, morphological, ultrastructural and biological investigation and chromosome analysis showed that the characteristic of transplanted tumor was identical to that of characteristics of human donor tumor. Through serial passages no metastatic signs were found grossly and under the microscope in the lymph nodes, liver and lung of the nude mice. Result also showed that the model retained some functions of the original tumor. The transplanted tumor could secret a-fetoprotein (AFP), r-glufamyl transpeptidase (r-GT). Acidic isoferritin (AIF) also could be detected. The tumor tissue of xenograft model was cultured in vitro in order to develop a permanent cell line. We found that the tumor specimen of the later passages grew more rapidly than the earlier ones. Up to now 3 cell passages were made. In this paper, a reliable animal model of human hepatocellular carcinoma is provided for studies of clinical diagnosis, treatment, antitumor drug screen test, etc.
Routine examination of pathologic sections in 500 cases of primary gastric adenocarcinomas was carried out by light microscopy. Regions of hepatocellular carcinomatoid differentiation were discovered in 12 of the 500 cases. In 11 of them, histopathologic features were described in great detail and the hepatocellular carcinomatoid regions were studied by four kinds of immunohistochemistrical methods. The results indicate that positive staining for AFP was seen in 9 cases but negative in 9 controls, weakly positive for CEA in 10 cases, but strongly positive in 8 controls. Staining for alpha 1-AT and alpha 1-ACT showed no differences as compared to controls. The clinical pathological features and its relationship with AFP are discussed. It is suggested that hepatoid gastric adenocarcinoma is a subtype of gastric adenocarcinoma.
Nonconsolidated particles of ultra high molecular weight polyethylene are believed to be defects that adversely can affect the wear performance of total joint prostheses. The present study was done to determine the number, size, and distribution of these particles and to determine if their presence correlated with wear performance, as well as with other clinical and implant parameters. Forty retrieved and 7 new, never-implanted acetabular components were examined using light microscopy on thin cross sections. Particles were found in 92% of retrieved components and in all the new components. Particles in the retrieved components were either randomly distributed (32 components) or banded (with particles localized in regions approximately 1 mm below the outer surface of the component). No correlations were found between the number or area of particles and the wear performance or any of the clinical or implant variables. The presence of particles in the new implants was found to correlate with the length of time since the components had been radiation sterilized. For retrieved components, the density (and, therefore, the level of oxidative degradation) was high in the areas of banded particles. For new components, the density was higher the longer the time since sterilization. Nonconsolidated polyethylene particles are prevalent in total replacements but their source and cause are unknown. The results of this study show that they do not appear to affect or correlate with the length of implantation of acetabular cups. However, they still may be expected to adversely affect performance in cases where large numbers of particles are banded together near articulating surfaces of high stress environments such as found in the knee.
A modification of the transbasal approach of Dorome called extensive subfrontal approach and the surgical results with this approach in 22 cases are presented. Bilateral frontal craniotomies incorporated with the removal of orbital ridges and part of the orbital roofs were fashioned en bloc. It may give rise to good exposure of the midline lesions of the anterior, middle and posterior skull base, minimizing the need for the retraction of frontal lobes. There was no surgical mortality in this series of cases. Of the 20 cases with tumors, total resections were achieved in 11 cases, subtotal or large resections in 4 cases and partial resection in one case. Two patients with spontaneous rhinorrhea were successively treated surgically. 21 patients had a follow-up with a time ranging from 1-11 years (a mean of 3 years). 15 patients resumed their jobs with no evidence of recurrence of the original disease, and 5 patients able to live self-care. One patient with an olfactory neuroblastoma died 3 years after the operation owing to relapse of the tumor.
On the basis of experimental study, we applied multiple subpial transection (MST) to treat 50 patients with intractable epilepsy in which epileptigenic lesion involved functional areas such as pericentral gyrus, postcentral gyrus, Broca's area, Wernicke's area, visual cortex, etc. They were followed up for 6 to 40 months. Complete control of seizures was obtained in 32 patients, significant reduction of seizure (more than 50%) in 13, reduction (less than 50%) in 3, and no effect in 2. The total effective rate was 96%. No functional defect was found in all patients. The mechanism of the disease and surgical technique were discussed in detail. We consider that MST could replace some standard excisional therapy for local epilepsy.
The foramen arcuale of vertebral artery of altas is one of the causes of vertigo. Leven cases of the cervical vertigo caused by foramen arcuale were operated on. The patients were followed up for 3-6 years. The results were satisfactory. The mechanism of inducing vertigo by foramen arcuale was discussed. We demonstrated that excision of the foramen arcuale is available for cervical vertigo.