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Biomedical subjects

Z Li

Publications and source records attributed to Z Li.

At least 1,063 records · Page 59Linked to original sources

Factors influencing the identification of major genes in a complex disease genome scan.

A two-stage linkage strategy was employed to identify major genes for a simulated complex disease via a genome scan. The importance of several approaches for improving the ability to locate major genes has been illustrated. These approaches are: adjusting for covariates, ascertaining through multiple affected family members, increasing the sample size, and using multipoint linkage analysis.

Chromosome Mapping↗

Antagonism by ethanol of endotoxin-induced tissue factor activation in relation to the depressed endotoxin binding to monocyte-like U937 cells.

Our previous study has reported that ethanol (ETOH) partially inhibited the endotoxin (LPS)-induced tissue factor (TF)-activation in monocytes including blood peripheral monocytes as well as cultured leukemic U937 and THP-1 cells. The present study shows a strong correlation (r = 0.92; p < 0.01) between TF-activation and depression in LPS binding blocked by ETOH in U937 cells. The antagonism by ETOH of LPS binding was not due to a direct extracellular blockade, since ETOH did not affect the affinity of fluorescein isothiocyanate (FITC)-LPS or -anti CD14 mAb on U937 cells. After U937 cells were treated with 2 per cent (v/v) ETOH for 3 h, LPS binding was however drastically inhibited as shown by immunostaining with FITC-LPS which was viewed on a confocal laser scanning microscope. The results imply that cellular events of the ETOH effect mediate this inhibition of LPS binding. Anti-CD14 mAb (UCHM-1) inhibited LPS binding in a dose-dependent fashion, revealing a competitive specific binding to the LPS receptor. The results suggest that CD14 plays an important role in the recognition of LPS. FITC-UCHM-1 binding was significantly reduced in the cells pretreated with 2 per cent (v/v) ETOH for 3 h, indicating that ETOH modulates the ability to express CD14. CD14 expression was upregulated by priming with LPS which was offset by ETOH. Acetaldehyde, a possible metabolite of ETOH, was tested with no effect on CD14 expression. Taken together, our results show that ETOH downregulates the recognition of LPS, and suggest that the inhibitory action is likely to be mediated by the depression in CD14 expression which was also accompanied by a significantly altered membrane fluidity. Thus, the antagonism by ETOH of the binding of LPS results in a depression in the LPS-induced TF-activation.

Anti-Infective Agents, Local↗

Significance of macrophage tropism of SIV in the macaque model of HIV disease.

Microglia, alveolar macrophages, and Langerhans cells are representatives of cells of macrophage lineage that are susceptible to infection with HIV-1 and they play important roles in the pathogenesis of AIDS dementia, lymphoid interstitial pneumonia, and systemic viral invasion from mucosal surfaces, respectively. In contrast, elimination of CD4+ T cells with resultant development of immunosuppression and AIDS is thought to be reflective of the exclusive tropism of the virus for CD4+ T cells. Examination of these concepts in macaques infected with molecularly cloned strains of SIVmac suggested that all strains of the virus are both macrophage- and lymphocyte-tropic and that all aspects of pathogenesis including loss of CD4+ T cells are dependent on infection in both cell types. However, viral clones that caused productive lytic infection in macrophages were less virulent than those which caused persistent nonproductive infection. The former caused subclinical and even immunizing infections, whereas the latter caused activation and productive infection in CD4+ T cells, AIDS, and systemic infection, even after inoculation of the virus on mucosal surfaces. If these findings on SIVmac are relevant to HIV-1 disease, then demonstration that HIV-1 isolates are macrophage-tropic probably does not necessarily correlate with their pathogenic potential.

Acquired Immunodeficiency Syndrome↗

Acute effects of periarterial sympathectomy on the cutaneous microcirculation.

The clinical effects of peripheral sympathectomy on patients with vaso-occlusive disease are often dramatic and include relief of pain, improved quality of life, and healing of ulcers. Peripheral periarterial sympathectomy is known to increase skin temperature and to maximize the nutritional component of peripheral blood flow, but the pathophysiology of vaso-occlusive disease and the physiologic mechanisms of this treatment are unknown. In this study, the acute effects of periarterial sympathectomy were directly observed in a rabbit ear model of digital microcirculation (arterioles, arteriovenous anastomoses, and venules). The effects of periarterial sympathectomy on cutaneous perfusion and total flow were also examined using laser Doppler perfusion imaging and digital temperature measurements. The central auricular artery became dilated (50-100%) immediately after sympathectomy; the arterioles, arteriovenous anastomoses, and venules dilated to 165, 156, and 223%, respectively, at 30 minutes and to 187, 174, and 204%, respectively, at 60 minutes, relative to their baseline diameters prior to sympathectomy. Laser Doppler perfusion imaging values and ear temperatures were noted to increase after sympathectomy (8.9%, 3 degrees C), although the core temperature of the rabbit did not change. Thus, acute periarterial sympathectomy can (a) effectively reduce the vascular tone of the distal microvasculature and (b) increase total microcirculatory perfusion-cutaneous and thermoregulatory-by both venular and arteriolar dilation. Periarterial sympathectomy has the clinical potential to increase nutritional blood flow, thereby ameliorating the signs and symptoms of ischemia associated with thermoregulatory abnormalities. Dilation of the arteriovenous anastomoses, with a subsequent reduction in vascular resistance, may contribute to the increased cutaneous temperature noted after sympathectomy.

Anastomosis, Surgical↗

Enhanced proliferation and migration and altered cytoskeletal proteins in early passage smooth muscle cells from young and old rat aortic explants.

Smooth muscle cell (SMC) proliferation, migration, and cytoskeletal protein expression were studied in cultured cells obtained from the aortic explants of young (6-month) and old (30-month) Fischer 344XNB rats. Second-passage SMC were cultured on coverslips, and cytoskeletal fibers were examined by immunofluorescence microscopy using antibodies specific for smooth muscle myosin, alpha-smooth muscle actin, vimentin, desmin, and tubulin. The cytoskeletal fiber density was quantified as fluorescence intensity by confocal microscopy. The proliferation of SMC was analyzed from the growth curve of cells grown in culture from 0 to 14 days, and a Boyden chamber assay was used to quantify the SMC migration rate. The diameter of fresh SMC digested enzymatically from old rat aortae was 52.4% larger than that of the cells from young animals (20.0 +/- 3 microm vs 13.1 +/- 2 microm, P < 0.05). In SMC cultured from old animals, the intensities of smooth muscle myosin, alpha-smooth muscle actin, and vimentin decreased by 59.6, 41.2, and 54.8%, respectively; desmin and tubulin increased by 46.1 and 65.1% (all P < 0.001). Compared to SMC isolated from young rat aortae, the number of SMC cultured (second passage) from the old rat aorta was increased by 48.4, 27.2, and 26.9%, respectively, at Days 3, 7, and 14 in culture (P < 0.05, P < 0.01, and P < 0.001). The migration rate of SMC cultured from old rats was 59.3% higher than that of the cells obtained from young rats. These data show that alterations of the SMC cytoskeleton occur concomitantly with changes in SMC proliferation and migration rate during aging, suggesting that the age-associated changes in cytoskeletal proteins may play a role in remodeling of the aortic wall during aging.

Aging↗

Null mutation in the desmin gene gives rise to a cardiomyopathy.

A null mutation in the desmin gene has been introduced into the germ line of mice. Such mice develop and reproduce normally proving that desmin is not needed either for the formation of the heart or the alignment of functioning myofibrils. However, cardiovascular lesions and a skeletal myopathy were observed in growing and adult mice. In the present study we have carried out a detailed analysis of these cardiac lesions. Homozygous mutant mice, which were confirmed to lack expression of desmin mRNA and desmin protein in the heart, were revealed by electron microscopy to contain degenerating cardiomyocytes as early as 5 days post-partum. At 10 days post-partum and onwards the degeneration of cardiomyocytes gave rise to areas with an accumulation of macrophages, fibrosis and calcification preferentially in the inter-ventricular septum and the free wall of the right ventricle. The localization of the lesions mainly to these sites suggested that it is not the work load and contractions per se which were the pathogenic events leading to the cardiomyopathy. It might be that stress related to lengthening of the myocytes occur more in the right ventricle than in the left. At the ultrastructural level changes in the intercalated discs, disruption of the sarcolemma and supercontraction of myofibrils seemed to be the key events leading to cardiomyocyte death. Thus, the intermediate filaments are required to maintain the basic integrity of cardiomyocytes and especially the link between the intermediate filaments and the sarcolemma appear more important than previously realized.

Animals↗

Priming of T cells by heat shock protein-peptide complexes as the basis of tumor vaccines.

A number of heat shock proteins, or stress proteins, have been shown functionally as potent 'tumor rejection antigens', despite the fact that there are no single tumor-specific mutations in these proteins. Current studies have solved many aspects of this puzzle biochemically and immunologically. The proposal that heat shock proteins are not antigenic per se, but chaperone and present antigenic peptides to MHC class I molecules for recognition by T lymphocytes, has been mechanistically defined. This significance of this discovery is elaborated in the context of the importance of MHC molecules. The immunological principle and the practical vaccination strategy of the two major mammalian heat shock proteins, gp96/grp94 and hsp70 are discussed. It is also argued that extracellular heat shock proteins signal cell stress and tissue damage, and are involved in presenting peptides to the MHC class I pathway through professional antigen presenting cells. These results and ideas form the basis of a new generation of T-cell vaccines against tumors and intracellular organisms.

Animals↗

Effect of left ventricular outflow on flow convergence region on the left septal surface in ventricular septal defect.

The corrected shunt flow rate (Fc) and corrected defect orifice area (Ac) were calculated by modified equation F = 2 pi R2 (NL-VLVOT x Sin theta) in 23 patients with single membranous ventricular septal defect, in order to correct the effect of left ventricular outflow on flow convergence region on the left septal surface. The results indicated that Fc was closely correlated with Qp-Qs, and Qp/Qs measured by pulsed wave Doppler (r = 0.95 and r = 0.81 respectively, P < 0.001). And the correlation between Ac and the diameter of defect (Dd) measured directly in two-dimensional views was better than that between uncorrected defect orifice area (A) and the Dd (r = 0.98 and 0.69, respectively, P < 0.001). The shunt flow rate calculated by ideal equation F = 2 pi R2 x NL overestimated the actual shunt flow rate in ventricular septal defect, especially in membranous type. Our study concluded that Fc can be used for a more accurate evaluation of the shunt severity of ventricular septal defect.

Adolescent↗

Heat shock and the role of the HSPs during neural plate induction in early mammalian CNS and brain development.

We have investigated the early development expressional of the heat shock protein genes (hsps) and HSP synthesis and their role during neuroectoderm induction, differentiation and early CNS formation. The expression and kinetics of 90, 73/71, 47 and 27 HSPs on neuroectoderm differentiation was compared under normal and stressed conditions. The role of HSPs on neuroctoderm cell fate including thermotolerance and apoptosis using a whole in vitro embryo culture system was studied. Hsp expression appears closely linked in early mammalian development to critical differentiation and proliferation stages in early brain and heart formation. The hsps are developmentally activated around blastula stage and HSPs are constitutively expressed at high levels during neural tube closure and are heat shock responsive. Using both Northern analysis, confocal microscopy and whole mount in situ hybridisation we have identified the mRNA hsp transcripts and HSPs during organogenesis. HSPs were detected during neuroectoderm cell induction and differentiation with the hsp mRNA being tightly regulated during the cell cycle of neuroectoderm especially at early fore-, mid-, hindbrain and heart formation. The 'chaperone' functions of the HSPs are well known, recently during gastrulation the HSP47 and 27 have been shown to specifically bind and fold to nascent collagen and actin molecules respectively. This role is essential for the formation of the basement membrane, extra cellular matrix and neural crest migration during neural plate development. HSP function was observed by using anti-sense strategy, short '5 anti-sense cDNA' hsp oligonucleotides inhibited hsp expression during gastrulation in the whole embryo cultures. The developmental activation of the heat shock element (HSE) is essential to our understanding of the HSPs role in neuronal cell fate. Using specific polyclonal antibodies to HSF1 and 2 (Dr Nakai, Kyoto University) the expression of heat shock factors (HSFs) during neuroectoderm differentiation was examined. Using Western analysis, confocal microscopy and flow cytometry HSF1 and 2 were identified and studied under both normal and heat shocked conditions. During gastrulation higher levels of HSF1 and 2 were identified in the neuroectoderm layer especially in regions of the fore-, mid- and hindbrain. The heat shock response and activation of the HSPs 90, 70, 47 and 27 families have been correlated with HSF1 and 2. The HSF1 appears to be present in all early embryonic cells but appears not to bind to the HSE until early head fold stage at gastrulation when the presence of HSF2 is observed. During neuroectoderm differentiation the activation of HSF1 and 2 appears to correlate with high constitutive expression of many of the hsps specifically hsp90, 73, 71, 47 and 27 being tightly regulated by the cell cycle at neurulation.

Animals↗

Effects of cholinergic depletion on glutamic acid decarboxylase immunoreactivity in the somatosensory cortex of rats.

The purpose of these experiments was to determine the effects of cholinergic depletion on the morphology and staining density of barrels formed by glutamic acid decarboxylase-positive neuropil in the posteromedial barrel subfield of the somatosensory cortex. The density and distribution of glutamic acid decarboxylase immunoreactive neuropil were examined after highly selective lesions of cholinergic neurons in the nucleus basalis of Meynert with an immunotoxin, IgG 192-saporin. Glutamic acid decarboxylase immunoreactivity was also examined in animals subjected to a whisker-pairing experience and lesion of acetylcholine inputs from the nucleus basalis of Meynert. Seven to 9 weeks after intraventricular injection of the immunotoxin, animals were perfused with a zinc aldehyde fixative and glutamic acid decarboxylase immunoreactivity was examined in 30-micron tangential sections. Cholinergic depletion caused reduced glutamic acid decarboxylase immunoreactivity in selective regions of the posteromedial barrel subfield. The density of neuropil and cell bodies immunoreactive for glutamic acid decarboxylase was significantly reduced in septa and perimeters of barrel walls. The length, width, and area of barrels were reduced 10-20% in cholinergic-depleted animals compared with controls. The density of glutamic acid decarboxylase immunoreactivity in the hollow of barrels was not affected by this treatment. Whisker pairing did not significantly change the density of glutamic acid decarboxylase immunoreactivity in barrels. These observations are discussed in regard to how long-term cholinergic depletion affects the function of different fiber systems in the posteromedial barrel subfield cortex and how some sensory functions may be comprised.

Acetylcholine↗

Rice ragged stunt oryzavirus genome segments S7 and S10 encode non-structural proteins of M(r) 68,025 (Pns7) and M(r) 32,364 (Pns10).

The nucleotide sequences of genome segments S7 and S10 of a Thai-isolate of rice ragged stunt virus (RRSV) were determined. The 1938 bp S7 sequence contains a single large open reading frame (ORF) spanning nucleotides 20 to 1843 that is predicted to encode a protein of M(r) 68,025. The 1,162 bp S10 sequence has a major ORF spanning nucleotides 142 to 1,032 that is predicted to encode a protein of M(r) 32,364. This S10 ORF is preceded by a small ORF (nt 20-55) which is probably a minicistron. Coupled in vitro transcription-translation from the two major ORFs gave protein products of the expected sizes. However, no protein was visualised from S10 when the small ORF sequence was included. Proteins were expressed in Escherichia coli from the full length ORF of S7 (P7) and from a segment of the S10 ORF (P10) fused to the ORF of glutathione S-transferase (GST). Neither fusion protein was recognised by polyclonal antibodies raised against RRSV particles. Furthermore, polyclonal antibodies raised against GST-P7 fusion protein did not recognise any virion structural polypeptides. These data strongly suggest that the proteins P7 and P10 do not form part of RRSV particle. This is further supported by observed sequence homology (though very weak) of predicted RRSV P7 and P10 with those of rice dwarf virus (RDV) non-structural proteins Pns6 and Pns9, respectively.

Amino Acid Sequence↗

Predicting the structure of apolipoprotein A-I in reconstituted high-density lipoprotein disks.

In reconstituted high-density lipoproteins, apolipoprotein A-I and phosphatidylcholines combine to form disks in which the amphipathic alpha-helices of apolipoprotein A-1 bind to the edge of a lipid bilayer core, shielding the hydrophic lipid tails from the aqueous environment. We have employed experimental data, sequence analysis, and molecular modeling to construct an atomic model of such a reconstituted high-density lipoprotein disk consisting of two apolipoprotein A-I proteins and 160 palmitoyloleoylphosphatidylcholine lipids. The initial globular domain (1-47) of apolipoprotein A-I was excluded from the model, which was hydrated with an 8-A shell of water molecules. Molecular dynamics and simulated annealing were used to test the stability of the model. Both head-to-tail and head-to-head forms of a reconstituted high-density lipoprotein were simulated. In our simulations the protein contained and adhered to the lipid bilayer while providing good coverage of the lipid tails.

Amino Acid Sequence↗

Contraceptive practices of women requesting termination of pregnancy: a study from China.

In order to develop a program for prevention of unwanted pregnancies, we conducted a survey of contraceptive practices and reasons for contraceptive failures of 1520 women seeking abortion at eight large hospitals in Zheng Zhou City, Henan Province, P.R. China, during the period from March 1996 to May 1996. The most frequent cause of the unplanned pregnancy was contraceptive failure (71.9%) 61.7% (938) of these current pregnancies were potentially predictable by virtue of nonuse of contraception (427) or by recognition of contraceptive failures (511). Among the contraceptive failures, the proportion of condom mishaps was the highest (29.7%), next was IUD failures (23.5%), then rhythm miscalculation (15.9%). Most of abortion seekers (77.1%) used some contraceptive methods previously. But only 19.7% of them used a contraceptive method at the first sexual intercourse. Among 1520 abortion seekers. 57.6% had used condoms previously; 50.9% of the condom users had at least one instance of condom mishap. The rhythm method had been used by 31.7% of abortion seekers previously; 59.1% of the rhythm users had at least one instance of rhythm failure. Of the 16.8% of abortion seekers who had used pills, 58.0% of them had pill failures Among condom and pill failures, most of them (46.4% condom users and 56.0%, pill users) belonged to the users failure category (poor compliance). Of those seeking abortion 56.4% had experienced at least one instance of previous abortion; 5.3% had experienced previous abortions at least two times. Emergency contraception had been utilized by only 10 subjects prior to this current pregnancy.

Abortion, Induced↗

Health-related quality of life after ileoanal pull-through evaluation and assessment of new health status measures.

BACKGROUND & AIMS: Health-related quality of life (HRQL) after proctocolectomy is a critical parameter for management decisions in patients with chronic pancolitis. The aim of this study was to evaluate the HRQL of patients with ileoanal pull-through and to validate new, easy-to-administer HRQL measures. METHODS: The Sickness Impact Profile (SIP), Short Form 36 (SF-36), Rating Form of Inflammatory Bowel Disease (IBD) Patient Concerns (RFIPC), and the time trade-off (TTO) were used to measure HRQL of pull-through patients. The SF-36 and the RFIPC were validated. RESULTS: HRQL of patients with ileoanal pull-through was better than that of a national sample of patients with IBD (SIP and RFIPC) and similar to that of a normal population (SF-36). Physical and psychosocial subscales of the SF-36 correlated with the SIP, affirming the construct validity of the SF-36. The RFIPC results correlated with the SIP and SF-36 results, suggesting that it is also a valid health status measure for these patients. TTO results correlated with the physical subscales of the SIP and SF-36, reflecting the impact of physical health on this group. CONCLUSIONS: HRQL of patients with ileoanal pull-through is excellent. The SF-36 and RFIPC are valid health status measures that can be used by clinicians and researchers in these patients.

Adult↗

Uroguanylin is expressed by enterochromaffin cells in the rat gastrointestinal tract.

BACKGROUND & AIMS: Guanylin and uroguanylin are recently discovered intestinal peptides. Identifying the type of cell that synthesizes and secretes each peptide is an important step toward defining their physiological functions. However, the site of uroguanylin expression has not been identified, and the site of guanylin expression remains controversial (some studies implicate goblet cells, whereas others implicate enterochromaffin cells). The aim of the present study was to identify cellular sites of uroguanylin expression in the rat gastrointestinal tract and resolve the guanylin localization controversy. METHODS: Polyclonal antibodies against two independent regions of the uroguanylin prohormone were raised and used to evaluate prouroguanylin expression by Western blotting and immunohistochemistry. In parallel, uroguanylin mRNA was localized by in situ hybridization. RESULTS: Uroguanylin propeptide expression is high in proximal small intestine, low in stomach and distal small intestine, and almost undetectable in large intestine. Uroguanylin-expressing cells are identified as a subpopulation of enterochromaffin cells. CONCLUSIONS: Previous results showing guanylin expression in enterochromaffin cells appear to be a consequence of antibody cross-reactivity for epitopes conserved between proguanylin and prouroguanylin. Expression of uroguanylin in enterochromaffin cells is consistent with the hypothesis that uroguanylin is secreted both apically (into the lumen) and basolaterally (into the circulation).

Animals↗

Mobility of Zn, Cd and Pb in soils as affected by poultry litter extract--II. Redistribution among soil fractions.

The application of poultry litter to metal-contaminated soils may influence metal leaching and distribution of metals among soil fractions. Soil columns (one uncontaminated control, one metal-amended, and two metal-contaminated soils) were leached with H2O, CaCl2, EDTA, and poultry litter extract (PLE) solutions. After leaching, the soil samples in the columns were sequentially extracted for water soluble (WS), exchangeable (EXC), organic matter (OM), Mn oxide (MNO), amorphous Fe oxide (AFEO), crystalline Fe oxide (CFEO) and residual (RES) fractions. The OM fraction showed high retention for Zn from the PLE. The EDTA redistributed Zn, Cd and Pb from the EXC, OM and MNO fractions to the WS fraction. The PLE usually solubilized more Zn and Cd from the EXC fraction than CaCl2. Neither PLE nor CaCl2 mobilized Pb. The application of poultry litter on metal-contaminated soils might cause Zn and Cd redistribution from the EXC to the WS fraction and enhance metal mobility.

Journal Article↗

Mobility of Zn, Cd and Pb in soils as affected by poultry litter extract--I. Leaching in soil columns.

Application of poultry litter to cropland may increase metal mobility, because the soluble organic ligands in poultry litter can form water-soluble complexes with metals. In this study, one uncontaminated soil and two metal-contaminated soils were sampled. A portion of the uncontaminated soil was amended with Zn, Pb, and Cd at rates of 400, 200, and 8 mg kg(-1), respectively. Packed soil columns were leached with H2O, EDTA, CaCl2, and poultry litter extract (PLE) solutions separately. No leaching of Zn, Cd, and Pb with the PLE was found in the uncontaminated soil. The retention of PLE-borne Zn indicated the potential for Zn accumulation in the soil. A large portion of the metals was leached from the metal-amended soil, and EDTA solubilized more Zn, Cd, and Pb than CaCl2 and PLE. In the metal-contaminated soils, the leaching of Zn and Cd with PLE was consistently larger than that for CaCl2, indicating that these metals were mobilized by organic ligands. The PLE did not mobilize Pb in these soils. The utilization of poultry litter in metal-contaminated soils might accelerate the movement of Zn and Cd in soil profiles.

Journal Article↗