Polarization of Sigma + and Sigma -bar- hyperons produced by 800-GeV/c protons.
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Journal Article↗
Biomedical subjects
D Chen
Publications and source records attributed to D Chen.
Functional and phenotypic analysis of thymocytes in SCID mice. Evidence for functional response transitions before and after the SCID arrest point.
Thymocytes from severe combined immune deficient (SCID) mice undergo developmental arrest at an early stage, before most TCR gene rearrangement. They therefore represent a natural test case to assess those aspects of T cell development that are TCR independent. Multiparameter flow cytometry was used to analyze the array of immature phenotypes present in the SCID thymus at steady state, as defined by the markers CD4, CD5, Sca-1, NK1.1, CD44, heat-stable antigen (HSA), and IL-2R alpha. The results suggest a simple developmental block in SCID mice rather than a program of aberrant differentiation. SCID thymocytes displayed efficient, developmentally regulated functional responses. Approximately 20-25% of the cells, mostly within the IL-2R alpha +HSA+CD44low fraction, could be induced to express IL-2. This IL-2 inducibility was highly dependent on IL-1 costimulation, in agreement with the behavior of normal immature thymocytes. These results formally demonstrate that competence to express IL-2 is developed independently of TCR expression or gene rearrangement. Comparison of the response properties of various SCID thymocyte subsets indicated that IL-2 inducibility is first likely to be acquired at an early (Sca-1++CD44++HSAlow) stage. A later functional transition was revealed by comparing patterns of IL-2R alpha regulation in normal and SCID IL-2R alpha +HSA+CD44low thymocytes. The SCID thymocytes uniformly maintained IL-2R alpha expression on in vitro stimulation, whereas only a minority of the normal cells in the corresponding subset could do so unless IL-1 was also added. The SCID arrest point thus appears to separate the IL-2R alpha +HSA+CD44low stage into distinct early (TCR independent) and late phases. Normal cells that progress beyond the SCID arrest point appear to lose, rather than gain, competence to make various responses, even before they leave the IL-2R alpha +HSA+CD44low stage. A model is proposed in which discrete changes in functional competence define novel transitions in early thymocyte development, at least some of which may be linked to TCR-beta gene rearrangement before positive or negative selection.
Animals↗
Cloning and sequence of bone morphogenetic protein 4 cDNA from fetal rat calvarial cell.
A cDNA clone encoding bone morphogenetic protein 4 (BMP 4) has been isolated from a primary fetal rat calvarial cell cDNA library. Sequencing of this clone has revealed a single open reading frame encoding a 408 amino acid protein. Comparison of 5' noncoding exon 1 portion of this cDNA with that of human bone and prostate BMP4 cDNA shows that BMP4 gene expression may possess tissue specificity.
Amino Acid Sequence↗
Surface barrier and lower critical field in YBa2Cu3O7- delta superconductors.
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Journal Article↗
Evidence of L-arginine/nitric oxide pathway in endothelium and smooth muscle of human internal mammary artery.
UNLABELLED: The L-arginine-nitric oxide (NO) pathway was investigated in human internal mammary artery (HIMA) in vitro. HIMA rings were mounted in organ bath, and then incubated in Krebs buffer for 1 to 8 hrs, relaxing agents were tested. Under these conditions, L-arginine (0.1 microM - 1 mM) elicited only minor relaxation after 2 hr incubation, whereas with increased incubation time (4, 6, 8 hrs), the concentration-dependent relaxation to L-arginine increased significantly in endothelium-intact and -denuded vessels. NG-nitro-L-arginine (100 microM) or NG-monomethyl-L-arginine (100 microM) or methylene blue (2.7 microM) partially inhibited L-arginine relaxation. In endothelium-intact HIMA and in both types of rings A23187 (10 microM) and L-arginine (100 microM), respectively, increased the concentration of NO in medium and cGMP content of vascular tissues. These increases were partially inhibited by NG-nitro-L-arginine (100 microM) or methylene blue (2.7 microM). CONCLUSION: in smooth muscle of HIMA L-arginine-NO conversion is calcium independent, which is different from that in endothelium.
Acetylcholine↗
Three-dimensional visualization of the rotavirus hemagglutinin structure.
Three-dimensional structures of a native simian and reassortant rotavirus have been determined by electron cryomicroscopy and computer image processing. The structural features of the native virus confirm that the hemagglutinin spike is a dimer of VP4, substantiated by in vivo radiolabeling studies. Exchange of native VP4 with a bovine strain equivalent results in a poorly infectious reassortant. No VP4 spikes are detected in the three-dimensional reconstruction of the reassortant. The difference map between the two structures reveals a novel large globular domain of VP4 buried within the virion that interacts extensively with the intermediate shell protein, VP6. Our results suggest that assembly of VP4 precedes that of VP7, the major outer shell protein, and that VP4 may play an important role in the receptor recognition and budding process through the rough endoplasmic reticulum during virus maturation.
Animals↗
Protection against vaginal SIV transmission with microencapsulated vaccine.
Although protection in animal models against intravenous challenges with simian immunodeficiency virus (SIV) has been reported, no previous vaccines have protected against a heterosexual route of infection. In this study, five of six macaques were protected against vaginal challenge when immunized with formalin-treated SIV in biodegradable microspheres by the intramuscular plus oral or plus intratracheal route. Oral immunization alone did not protect. After a second vaginal challenge, three of four intramuscularly primed and mucosally boosted macaques remained protected. The data suggest that protection against human immunodeficiency virus vaginal transmission could be provided by microsphere-based booster vaccines when used to immunize women who are systemically primed.
Administration, Oral↗
Sickle erythrocyte-endothelial interactions in microcirculation: the role of von Willebrand factor and implications for vasoocclusion.
To determine the role of von Willebrand factor (vWF) in adhesion of sickle (SS) erythrocytes in microvascular flow conditions, we have perfused the ex vivo mesocecum vasculature of the rat with desmopressin, an analogue of vasopressin that causes the release of endothelial vWF. Analysis of vWF in the venous effluent of the isolated vasculature showed mainly the presence of extra-large molecular weight forms characteristic of endothelial vWF, which in the presence of desmopressin showed an average increase of 54%. Also, desmopressin induced a significant increase in adhesion of washed oxygenated (oxy) unseparated SS erythrocytes, accompanied by a persistent microvascular obstruction and a pronounced increase in the peripheral resistance (PRU). In contrast, infusion of SS deformable discocytes (SS2) in desmopressin-perfused vasculature resulted in a significant adhesion but not in persistent vasoocclusion, showing that SS2 discocytes alone are not sufficient for microvascular obstruction. Furthermore, SS4 erythrocytes (dense discocytes and irreversibly sickled erythrocytes) caused a persistent microvascular blockage and a significantly higher PRU than SS2 discocytes. However, the increase in PRU for SS4 erythrocytes following desmopressin treatment was 50% less compared with a corresponding increase for SS2 discocytes over the control values, which showed a smaller effect of desmopressin on the hemodynamic behavior of SS4 dense erythrocytes. Incubation of desmopressin-treated vasculature with anti-vWF antibodies resulted in a pronounced decrease in adhesion and significantly improved hemodynamic behavior of SS cells. Also, in untreated vasculature, similarly incubated with anti-vWF antibodies, there was almost complete inhibition of adhesion. Under the described perfusion conditions, antibodies to fibronectin and thrombospondin, as well as incubation of SS erythrocytes with anti-vWF antibodies did not affect adhesion. These results are compatible with a model for SS vasoocclusion in which extra-large vWF-mediated adhesion of deformable SS erythrocytes is the first step followed by an accelerated entrapment of dense SS erythrocytes.
Adult↗
Electrostatic sample-tip interactions in the scanning tunneling microscope.
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Journal Article↗
Comparison of cefoxitin and ceftizoxime in a hospital therapeutic interchange program.
OBJECTIVE: To determine whether (a) ceftizoxime can replace cefoxitin in the prevention and treatment of various infections in a major teaching hospital, (b) a previously applied two-stage intervention program is an effective method of instituting a therapeutic interchange of ceftizoxime for cefoxitin and (c) the replacement of cefoxitin with ceftizoxime results in a more cost-effective therapy. DESIGN: Two-phase, open, sequential study. SETTING: Tertiary care teaching hospital. PATIENTS: One hundred patients who received cefoxitin during the 6 months immediately before the start of the interchange program (phase 1) and 100 who received ceftizoxime during the 6 months immediately after the start of the program (phase 2) were randomly selected. RESULTS: The demographic characteristics of the two patient groups were similar except for sex (p < 0.05). The cefoxitin doses were usually given every 6 hours (in 33% of the cases) or every 8 hours (in 61%), whereas the ceftizoxime doses were usually given every 12 hours (in 98%). Prescriber distribution was stable throughout the study period, the Department of General Surgery being responsible for about 70% of the orders. Prophylactic indications accounted for over 60% of the treatment courses. The proportion of prophylactic treatment courses that resulted in a successful clinical outcome did not differ between the two groups (cefoxitin 92% and ceftizoxime 91%). Of the empiric or directed treatment courses clinical success or improvement was observed in 89% of the cefoxitin and 91% of the ceftizoxime recipients. Microbiologic eradication was seen in 65% of the cefoxitin and 90% of the ceftizoxime directed treatment courses. Pathogens isolated during therapy were similar in the two treatment groups. Diarrhea was the most common adverse effect, occurring in 8% of the cefoxitin and 10% of the ceftizoxime recipients; no Clostridium difficile or C.-difficile-producing toxin was identified in these patients. The ceftizoxime therapy was 36% less expensive than the cefoxitin therapy on average, and the annual savings was estimated to be $83,123. An estimated 5615 drug doses were avoided annually, for an additional savings of $24,875 in drug administration. Therefore, the total estimated annual cost savings resulting from this two-stage interchange program was $107,998. Given the cost of $4856 to implement and maintain the program, the estimated net savings for the first year was $103,142. CONCLUSION: Ceftizoxime can replace cefoxitin in the prevention and treatment of various infections. The form of evaluation described herein is valuable when any formulary modification is being considered in a hospital.
Adult↗
Antinociceptive activity of liposome-entrapped calcitonin by systemic administration in mice.
Porcine calcitonin (pCT) encapsulated in sulfatide-containing reverse-phase evaporation vesicles (REVs) was shown to induce long-lasting and dose-dependent antinociceptive effect by systemic injection in mice. Its antinociceptive activity is found to be dependent on the route of administration. In contrast, neither unencapsulated pCT nor pCT encapsulated in sulfatide-free REVs was effective. These results suggest that pCT entrapped in sulfatide-containing liposomes might be able to cross the blood-brain barrier (BBB) and to produce central antinociception in mice.
Analgesics↗
Effects of low level prenatal 60Co gamma-irradiation on postnatal growth and behavior in mice.
Pregnant Kun Ming strain mice were exposed to a total dose of 0, 0.1, 0.2, or 0.4 Gy from 60Co gamma-rays from the 13th to the 18th days of gestation. An overall delay of the appearance of two physiologic markers (pinna detachment, eye opening) and the age of acquisition of four reflexes (surface righting, air righting, auditory startle, visual placing) was observed in offspring exposed to 0.2 or 0.4 Gy in utero. Postnatal growth retardation, shortened length of hanging time, inhibited exploratory activity in the hole board test (decreased number of head-dipping), and hyperactivity in the open field test (shortened latency to leave the center area and increased number of squares entered) were also found among the offspring exposed to 0.2 Gy or more in utero. The results indicate that 0.1-0.2 Gy may represent a threshold range in mice for certain physiologic and behavioral effects resulting from continuous exposure to 60Co gamma-rays on the 13th-18th days of gestation.
Animals↗
Magnesium cardioplegia prevents accumulation of cytosolic calcium in the ischemic myocardium.
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Animals↗
Influence of local finger cooling on laser Doppler flux and nailfold capillary blood flow velocity in normal subjects and in patients with Raynaud's phenomenon.
We examined the influence of local cooling (-15 degrees C, 60 sec) on blood flow velocity in nailfold capillaries and on laser Doppler flux (LDF) at the fingertip in 12 patients with primary Raynaud's phenomenon (PRP) and 13 patients with secondary Raynaud's (SRP) in comparison with 10 health controls. Skin temperature at the pulp of the finger decreased significantly during local cooling in RP but not in controls. LDF before cooling was comparable between patients and controls and dropped significantly under cooling. Flux motions at the fingertip were present in all individuals with 7.9-9.1 cycles/min. Flux motions persisted throughout the cooling test and faded away in 5 patients (1 PRP, 4 SRP) with cooling. Frequency of LDF motions was little influenced by a change in skin temperature. The amplitudes were dampened in relation to the drop in LDF level during local cooling in patients with RP. We conclude that LDF does respond to local cooling of the fingertip by significant decrease of perfusion but not with regard to flux motions. The wide overlap of the single values does not allow as good a separation of patients with RP from controls as capillary microscopy.
Adolescent↗
Rescue of infectivity by in vitro transcapsidation of rotavirus single-shelled particles.
We investigated the possibility of rescuing the infectivity of noninfectious single-shelled rotavirus particles by in vitro transcapsidation. The soluble outer capsid proteins VP4 and VP7 were prepared by EDTA treatment of double-shelled (ds) particles of SA11-4F (G serotype 3), followed by removal of single-shelled (ss) particles by three sequential rounds of centrifugation. Ss-particles of B223 (G serotype 10) were prepared by two cycles of EDTA treatment of ds-particles followed by iospycnic CsCl gradient purification. A trace of infectivity (< 1000 PFU/ml) was always detected in the preparations of ss-particles, while no detectable infectivity (< 5 PFU/ml) was present in the preparations of outer capsid proteins. By mixing soluble outer capsid proteins VP4 and VP7 purified from SA11-4F and ss-particles of B223 at acidic pH (5.4), ds-like, transcapsidated particles were obtained. The transcapsidated particles were indistinguishable from genuine ds-particles by negative stain electron microscopy. However, the particles had a density intermediate between that of ds- and ss-particles. Protease-resistance studies revealed that VP7 was assembled onto transcapsidated particles in a resistant (native) form, but VP4 associated with the particles was completely protease sensitive. Viral infectivity was rescued by in vitro transcapsidation as indicated by a 500- to 1000-fold increase over background. The increased infectivity was neutralized by antiserum against SA11 (outer capsid donor), but not by antiserum against B223 (ss-particle donor). The transcapsidated particles formed small plaques like the B223 parent, and all the infectious progeny viruses contained the B223 genome. These results strongly indicate that the observed increase of infectivity was the result of in vitro transcapsidation.
Animals↗
Rescue of infectivity by sequential in vitro transcapsidation of rotavirus core particles with inner capsid and outer capsid proteins.
We recently developed an in vitro transcapsidation system in which infectivity of single-shelled (ss) rotavirus particles was successfully rescued (Chen and Ramig, Virology [1993]). Here, we report the rescue of infectivity of rotavirus core particles using virus strain B223 (G serotype 10) as the core donor and strain SA11-4F (G3) as the capsid donor. Core particles of B223 were obtained by CaCl2 treatment of B223 ss-particles followed by isopycnic CsCl gradient centrifugation. Inner capsid protein VP6 of SA11-4F was prepared by CaCl2 treatment of SA11-4F ss-particles, followed by removal of core particles by two rounds of centrifugation. Outer capsid proteins VP4 and VP7 of SA11-4F were prepared by EDTA treatment of ds-particles, followed by three rounds of centrifugation to remove ss-particles and minimize residual infectivity. No infectivity (< 3 PFU/ml) was detectable in any of the donor preparations. Transcapsidated ss-particles were obtained by mixing B223 core particles and a 5-fold excess of SA11-4F VP6 at neutral pH. The formation of transcapsidated ss-particles was confirmed by electron microscopy, protein composition analysis, and density determination. Along with the formation of ss-particles by in vitro transcapsidation, some infectivity was also detected and transcriptase activity was reconstituted. Semi-purified transcapsidated ss-particles were then mixed with SA11-4F outer capsid proteins VP4 and VP7 at acidic pH to obtain transcapsidated ds-particles, as described previously. The formation of ds-like particles was also confirmed by electron microscopy, protein composition, and density determination. As the result of formation of transcapsidated ds-like particles, viral infectivity increased significantly (80-fold) relative to that of transcapsidated ss-particles. The infectivity of transcapsidated ds-particles was neutralized by polyclonal anti-SA11 serum, but not by polyclonal anti-B223 serum. The transcapsidated particles formed small plaques like B223 (core donor), and all the progeny plaques contained B223 genomes. These results demonstrate that the infectivity of rotavirus core particles can be rescued by sequential addition of inner and outer capsid proteins in vitro.
Antigens, Viral↗
Effect of omeprazole-evoked hypergastrinemia on ultrastructure of enterochromaffin-like cells in the stomach of portacaval-shunted rats.
The histamine-producing enterochromaffin-like (ECL) cells in the acid-producing portion of the rat stomach responded to long-standing hypergastrinemia (omeprazole treatment daily for 8-10 weeks) with hypertrophy (and hyperplasia) and with a reduced number of granules and vesicles per unit cytoplasm. There was a reduction in the ratio of electron-dense granules versus vesicles and an increase in the profile diameter of the vesicles. Also, portacaval shunting (PCS) induced changes in the ECL cells, manifesting (i) as an increase in cell number and size, and (ii) as a reduced number of granules and vesicles per unit area. The cytoplasmic granules and vesicle profiles were enlarged, and the ratio of granules versus vesicles was reduced. The combination of PCS and long-standing hypergastrinemia (omeprazole treatment) produced a greatly enhanced ECL cell hypertrophy (and hyperplasia) and a marked reduction in the number of granules. The ratio of granules versus vesicles was markedly reduced while the profile diameters of both granules and vesicles were increased. The relative predominance of very large vesicles (vacuoles) was a prominent feature of the ECL cells in these rats.
Animals↗
Time-dependent changes in enterochromaffin-like cell kinetics in stomach of hypergastrinemic rats.
BACKGROUND: Hypergastrinemia has been claimed to cause first hyperplasia and then dysplasia/neoplasia of enterochromaffin-like (ECL) cells in rat stomach. The growth is thought to reflect an accelerated self replication rate of mature ECL cells. The cytokinetics and the histidine decarboxylase (HDC) activity of the ECL cells were investigated during sustained hypergastrinemia. METHODS: Hypergastrinemia was evoked by omeprazole (400 mumol.kg-1 x day-1 orally) for up to 1 year. Immunocytochemistry for histamine was used to determine the ECL cell density and combined with [H3]-thymidine autoradiography to establish the labeling index (LI), i.e., the proportion of the ECL cells that has incorporated [H3]thymidine. RESULTS: The ECL cell density increased progressively for 10-20 weeks in response to the hypergastrinemia and remained at a plateau for the remainder of the study. The hyperplasia was diffuse with additional micronodules at 52 weeks. The ECL cell Ll was maximally elevated after 1-2 weeks and declined to control values after 10-20 weeks of treatment. In contrast, the HDC activity remained elevated for the duration of the study. CONCLUSIONS: The ECL cell hyperplasia reflects the transiently elevated ECL cell Ll during the early phase but is not associated with an accelerated rate of mitosis during the 10-52 weeks period. Even though with time gastrin seems to loose its ability to sustain a high ECL cell Ll it retains its ability to maintain a high HDC activity.
Animals↗