Search PubMed⌕ Search

Biomedical subjects

Y X Fu

Publications and source records attributed to Y X Fu.

At least 91 records · Page 5Linked to original sources

Necessary and sufficient conditions for the existence of linear invariants in phylogenetic inference.

The necessary and sufficient conditions for the existence of linear invariants under semigroups of probability transition matrices are derived. It is found that a biologically meaningful nucleotide substitution model has linear invariants if and only if it is a submodel of one of the three most general models, which include the so-called balanced and unbalanced transversion models. Each of these three general models is a nucleotide substitution model with six parameters.

DNA↗

Dynamics of cytonuclear disequilibria in finite populations and comparison with a two-locus nuclear system.

We study the behavior of cytonuclear disequilibria in a finite monoecious population due to (1) random drift alone, (2) random drift and mutation, and (3) random drift and migration, using exact results on the RUZ (Random Union of Zygotes) model and diffusion approximations. We also show that the RUG (Random Union of Gametes) model is not suitable for a cytonuclear system. The study is also accompanied by a comparison with a two-locus nuclear system. We show that in a finite population of size N without mutation, the rate of decrease of the cytonuclear allelic disequilibrium is the same as that in the corresponding unlinked two-locus nuclear system. The principal rate of decrease of variance in allelic disequilibrium in a cytonuclear system is slightly faster than that in the corresponding nuclear system. However, the expected value of the variance in cytonuclear disequilibria is larger than that in a two-locus nuclear system for at least the first N generations. With mutation, the expected value of steady state variances of both systems are about the same; however, the normalized variance in linkage disequilibrium sigma 2d of the cytonuclear system is about twice as large as that for the corresponding nuclear system. For the migration process, two sets of steady state solutions are provided, one for the variables before migration and the other for the variables after migration. Diffusion approximations for both the principal rate of decay and steady state solutions in both systems are found to be satisfactory. A more accurate backward diffusion equation for a two-locus nuclear system is provided when the recombination fraction R is large.

Animals↗

[Experiences in diagnosis and treatment of chronic subdural hematoma].

Diagnosis and treatment of 95 patients with chronic subdural hematoma (CSDH) are presented. There were 92 males, 56 patients (59%) over 51 years old and 66 of them with history of head injury. The majority of our patients appeared increased intracranial pressure. Mental confusion and incontinence of urine and stool usually occurred in senile patients. Ultrasonic and electroencephalography examination were helpful in location of the hematoma. Cerebral angiography could make actual diagnosis. CT scan were more useful in diagnoses of CSDH and may discover multiple hematomas. If CSDH image were iso-dense on CT scan cerebral angiography should be performed. In the early years extirpation of CSDH including the capsule was performed. Now an irrigation drainages by cranial bur hole was performed usually. 5 patients had complication. The mechanism and prevention of CSDH are discussed.

Adolescent↗

On the design of genome mapping experiments using short synthetic oligonucleotides.

The DNA of an organism can be digested into smaller fragments, stored individually as clones in phage, for example, to create a clone library, and retrieved later, when needed. The original ordering of fragments is lost in the process of creating the library. Hence, it is important to be able to place clones in order according to their position along chromosome(s), and this process is referred to as "in vitro reconstruction" or "contig mapping" of an organismal genome. Clones in the phage library can be assigned binary call numbers by scoring each clone for hybridization (0 or 1) with a battery of short manufactured DNA sequences called synthetic oligonucleotides or with restriction enzyme digests of each clone. Those clones with similar call numbers are placed close together in the ordered library. We address the design question of how many clones and probes to use to carry out in vitro reconstruction of an organism's chromosomes. This physical mapping problem is placed in the context of coverage problems in geometrical probability. Various statistics are developed to summarize how an ordered library covers a chromosome, the extent of clone overlap, and the similarity between clone call numbers. Several tests for whether clones overlap are given, together with their power properties. A simulation study is used to determine how robust some of the tests for clone overlap are to model violations. Tables are presented for researchers to choose the number of clones and probes on the basis of both power and technical considerations surrounding the hybridization experiments.

Animals↗

Role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. II. Down-regulation of macrophage-mediated cytotoxicity by tumor-derived granulocyte-macrophage colony-stimulating factor.

Peritoneal elicited macrophages (PEM) from mammary tumor-bearing mice have a decreased capacity to become cytotoxic against syngeneic, allogeneic, and xenogeneic target cells upon in vitro stimulation with LPS, as compared with PEM of normal mice. A regulatory mechanism other than PG release is suggested because the addition of both indomethacin and LPS to macrophage cultures from tumor-bearing mice caused no changes in their cytotoxic capability. Because tumor products have been implicated in the down-regulation of immune responses, we investigated whether pretreatment with supernatants from the tumor cell line DA-3, derived from the in vivo mammary adenocarcinoma D1-DMBA-3, affects the cytolytic capacity of macrophages. This treatment inhibits, in a dose-dependent fashion, the ability of stimulated normal PEM to kill target cells. Partial purification of DA-3 cell line supernatant showed that most of the inhibitory activity was exerted by factors with a molecular mass greater than 10 kDa and less than 30 kDa. However, slight inhibition could also be observed with fractions containing molecules less than 10 kDa. The data suggest that more than one factor released by the mammary tumor cells may be involved in the down-regulation of macrophage-mediated cytotoxicity. Because the DA-3 cells constitutively produce granulocyte-macrophage CSF (GM-CSF), which has a molecular mass of 27 kDa, we pretreated PEM from normal mice in vitro with rGM-CSF for 24 h. This resulted in a dose-dependent decrease in their capacity to kill tumor target cells upon LPS stimulation. Furthermore, PEM from normal mice injected with rGM-CSF for 25 days displayed a profound decrease in their cytolytic ability against DA-3 targets upon in vitro stimulation with increasing amounts of LPS. The pretreatment of PEM from normal mice with a combination of DA-3 cell supernatants and specific anti-GM-CSF partially neutralized the inhibitory effect of the DA-3 supernatant on macrophage tumoricidal capability. These results indicate that tumor-derived GM-CSF is an important factor involved in the decreased macrophage cytotoxicity during mammary adenocarcinoma progression.

Adenocarcinoma↗

On the association of restriction fragment length polymorphisms across species boundaries.

We study the expected values of gametic-phase disequilibrium in both nuclear and cytonuclear systems in a finite population composed of reproductively isolated subpopulations. Random drift alone within each subpopulation will generate permanent overall non-zero gametic-phase disequilibrium in both a two-locus nuclear system and a cytonuclear system unless the population has an overall initial disequilibrium of zero. We derive formulae for the expected overall disequilibrium when mutation is involved and demonstrate that these values decay to zero at an extremely slow rate compared with the decay of the expected disequilibria within each subpopulation.

Animals↗

The role of tumor-derived cytokines on the immune system of mice bearing a mammary adenocarcinoma. I. Induction of regulatory macrophages in normal mice by the in vivo administration of rGM-CSF.

Using a dimethylbenzanthracene-induced immunogenic nonmetastatic murine mammary adenocarcinoma in BALB/c mice, our previous work has shown that splenocytes from tumor bearers have reduced responses to both mitogens and Ag including tumor-associated Ag. NK and cytotoxic T cell activities are also reduced in splenocytes of tumor bearers. Mac-1+2+ macrophages induced in mammary tumor bearers are capable of down-regulating lymphocyte responses to mitogens and tumor-associated Ag by cell to cell contact interaction and increased PGE2 production. We have found that the tumor constitutively releases a granulocyte-macrophage (GM)-CSF-like factor in vivo and in vitro, which may be responsible for the systemic increase in cells of the macrophage lineage in tumor-bearing mice. A tumor cell line established from the in vivo tumor expresses and releases GM-CSF as shown by Northern and Western blot analyses. Daily i.p. injections for 3 wk of 10,000 U of rGM-CSF into normal mice induces hemopoietic and immunologic alterations similar to those observed in tumor bearers. Mac-1+ and/or Mac-2+ macrophages can also be detected in the spleens and bone marrow of the mice treated with rGM-CSF. Additionally, splenocytes from rGM-CSF-treated mice have reduced responses to mitogens and their peritoneal exudate cells can cause in vitro down-regulation of proliferative responses of lymphocytes from normal mice. The suppression can be partially reversed by the addition of indomethacin to the cultures suggesting that PGE2 may contribute to the effect. rGM-CSF enhances the in vitro release of PGE2 by the spleen, bone marrow, and peritoneal cells of normal mice. These data indicate that the high levels of GM-CSF constitutively produced by the tumor may be responsible for the hemopoietic changes and immunologic alterations observed in tumor-bearing mice.

Adenocarcinoma↗

Splenic macrophages from tumor-bearing mice co-expressing MAC-1 and MAC-2 antigens exert immunoregulatory functions via two distinct mechanisms.

Tumor burden has been shown to induce a variety of phenotypic and functional changes in the cellular constituents of the host's immune system. These changes have been implicated as mechanisms by which tumors avoid rejection. Studies of BALB/c mice bearing a D1-DMBA-3 mammary adenocarcinoma showed alterations of the splenocyte populations. There was a five-fold increase of macrophages (M phi) that were phenotypically and functionally analyzed to establish their role in tumor-induced modifications of the host's immune response. Monoclonal antibody staining defined a Mac-1+2+ population which comprised up to 20% of the splenocytes in tumor-bearers (TB), but is negligible in spleens from normal mice. These Mac-1+2+ M phi were found to mediate down-regulation of both polyclonal and antigen-specific T and B cell responses in vitro and in vivo. Although B cell responses were suppressed via prostaglandin E2 (PGE2) production by the TB M phi, T cell responses were relatively refractory to PGE2-mediated down-regulation. Instead, they were suppressed by a contact-dependent T cell-M phi interaction. Furthermore, tumor-derived factors such as granulocyte-M phi colony-stimulating factor (GM-CSF) seem to play an important role in the induction and expansion of the Mac-1+2+ M phi. These cells appear to mediate down-regulation of the host immune responses by at least two distinct mechanisms: 1) PGE2 production and 2) a cell contact-dependent, but non-major-histocompatibility-complex-specific, interaction.

Adenocarcinoma↗

Necessary and sufficient conditions for the existence of certain quadratic invariants under a phylogenetic tree.

Invariants are functions of the probabilities of state configurations among lineages, with expected values equal to zero under certain phylogenies. For two-state sequences, the existence of certain quadratic invariants requires a symmetric substitution model. For sequences with more than two states, the necessary condition for the existence of certain quadratic invariants in terms of independent events is much stronger than symmetry. For DNA sequences, only three parameters are allowed in the substitution model, which includes Kimura's two-parameter model as a special case.

Base Sequence↗

Recognition of a single hsp-60 epitope by an entire subset of gamma delta T lymphocytes.

We can conclude that a large subset of gamma delta cells, present in both murine newborn thymus and in adult spleen, respond to the stress protein, hsp60. hsp60 seems to be stimulatory whether it is derived from a foreign pathogen such as mycobacteria, or whether it originates from the mouse's own cells. The gamma delta cells that respond to this antigen bear very similar receptors, all expressing V gamma 1 and most expressing V delta 6, although their junctional variations indicate that not all members of the subset stem from clonal expansion of only one or a few cells. The hsp60-reactive subset has not at this time been shown to "home" to an epithelial location, in contrast to other known gamma delta cell subsets, and may rather carry out its functions while in circulation. Whether the hsp60 antigen requires a "presenting" molecule remains at this point unclear, but because the gamma delta cells all respond to a synthetic peptide representing an epitope of hsp60, presentation is implied. Human gamma delta cells that respond to PPD from mycobacteria, as do the mouse hsp60-reactive gamma delta cells, have also been described, many as members of a major subset in peripheral blood, although only rarely have these been reported to respond to mycobacterial hsp60. The antigenic source in PPD for these cells has not yet been determined, but as for the mouse, a low molecular weight peptide appears to be sufficient for stimulation (P. Brennan and R. Modlin, personal communication). The PPD-reactive gamma delta cells, when their receptors have been characterized, have been found to express a V gamma 9+ chain. Some evidence indicates that these cells can also recognize self hsp60; hence, in several ways, this human subset has characteristics similar to the mouse hsp60-reactive subset. Perhaps gamma delta cells that respond to hsp60 play an important role, in both mice and humans, in the detection of transformed self cells or cells containing intracellular pathogens, that escape detection by alpha beta T cells.

Amino Acid Sequence↗

Food-induced asthma in China: an analysis in 40 cases.

Forty patients with a history of recurrent attacks of asthma after ingesting certain foods are described. All of these individuals had positive intracutaneous skin tests to at least one of the food allergens which was suggested by their history to cause an attack. In four of these patients, a bronchoprovocational challenge was performed with an aerosolized extract of the potential offending food. Clinical manifestations, possible mechanisms, and diagnostic measures for food-induced asthma are discussed.

Adult↗

Expansion of immunoregulatory macrophages by granulocyte-macrophage colony-stimulating factor derived from a murine mammary tumor.

Using an immunogenic nonmetastatic murine mammary adenocarcinoma (D1-DMBA-3) induced in BALB/c mice by dimethylbenzanthracene, we have previously shown that splenocytes from tumor bearers have depressed lymphocyte responses to mitogens and antigens, including tumor-associated antigens. In addition, they display decreased natural killer and T-cell cytotoxic activities. Macrophages from tumor-bearing mice appear to be responsible for the suppression of T- and B-cell responses to concanavalin A, lipopolysaccharide, and tumor-associated antigens observed in tumor bearers. The appearance of these macrophages in the spleen tightly parallels the progressive growth of the tumor and the concomitant immunosuppression. Simultaneously high levels of macrophage progenitors were observed in blood, bone marrow, lung, and liver. A significant increase of colony-stimulating activity of the granulocyte-macrophage lineage was detected in the sera from tumor-bearing mice. Higher levels of this colony-stimulating activity (CSA) were detected in tumor cystic fluid as compared with the levels in serum. A tumor cell line established in vitro from the D1-DMBA-3 in vivo tumor produces high levels of a factor with CSA in culture supernatant fluids. Partial purification of the CSA from the tumor cell line supernatants was achieved using CentriCell ultrafiltration and SephacrylS-300 chromatography. These studies revealed that the molecular weight of the colony-stimulating-like factor is 32,000 to 35,000. The morphology of the colonies obtained in cultures using this factor is similar to that of the colonies that develop in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) but not with macrophage colony-stimulating factor (M-CSF). CSA from tumor cell supernatants was neutralized by antiserum to GM-CSF but not with anti-M-CSF or anti-granulocyte colony-stimulating factor (G-CSF). Macrophages from bone marrow or peritoneal exudates from normal mice cultured with tumor supernatant for 2 to 3 days strongly inhibit normal splenocyte responses to concanavalin A and lipopolysaccharide. The data suggest that the tumor releases a GM-CSF that alters the hemopoietic system and induces or expands macrophages, which exert a suppressive function on the immune system of tumor-bearing mice.

Animals↗

A double-blind trial of oral immunotherapy for Artemisia pollen asthma with evaluation of bronchial response to the pollen allergen and serum-specific IgE antibody.

Eighteen asymptomatic Artemisia pollen asthma patients with normal pulmonary function were selected for a double-blind trial of oral immunotherapy. Each patient had a positive skin test to Artemisia pollen extract and also a positive bronchial challenge response to the same extract. The patients were randomly assigned to active treatment or placebo group and received intensive oral administration of Artemisia pollen extract over a 50-day course. The nine patients who received the active treatment ingested a cumulative dose of 396,652 PNU and showed a significant decrease in serum-specific IgE antibodies (P less than .05) and a significant reduction in bronchial sensitivity to the same extract (P less than .01). The changes in these two variables correlated well (r = .8787, P less than .01). The nine patients who received the placebo showed no significant changes in serum-specific IgE or bronchial sensitivity to Artemisia pollen extract. Follow-up of two cases with the same extract showed that the reductions in serum-specific IgE as well as bronchial sensitivity induced by oral immunotherapy were maintained for 3 months.

Administration, Oral↗

NMR study on the major components in hematoporphyrin derivative YHPD.

The hematoporphyrin derivative YHPD, a China-made product, has been clinically used in photodynamic therapy of tumors as a good photosensitizing drug. The NMR study on the structure of its major components is reported here. In terms of high performance liquid chromatography (HPLC) four major components A, B, C and D were isolated. The NMR results showed that the component A is O-acetylhematoporphyrin, B and C are two isomers of vinyldeuteroporphyrin. The spectra of 2-dimensional homonuclear correlation NMR, 2-dimensional NOE (nuclear overhauser enhancement), 13C-NMR and off-resonance as well as FAB (fast atom bombarding) mass spectrum of component D indicate that it is a protoporphyrin dimer linked by carbon-carbon bond. This finding may provide a chemical basis for understanding the difference in biological activity between YHPD and other foreign commercial HPD, as well as the composition of clinically used alkali-treated HPD and its effective component.

Chromatography, High Pressure Liquid↗