Spin-exchange-pumped 3He and 129Xe Zeeman masers.
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Journal Article↗
Biomedical subjects
B Wu
Publications and source records attributed to B Wu.
Effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig ventricular cells.
We examined the effects of cibenzoline, a new class Ia antiarrhythmic drug, on various membrane ionic currents and action potentials of guinea-pig single ventricular cells, using patch clamp techniques in whole-cell configuration. Action potentials and the membrane currents were evoked at a clamping rate of 0.2 Hz, and all experiments were performed at 32-33 degrees C. 1) Cibenzoline (5, 10 and 30 microM) decreased the Na+ current (INa), in a concentration-dependent manner. The concentration of the half-maximal inhibition (Kd) for INa was estimated to be 7.8 microM. 2) In addition to the inhibition of INa, this drug (5, 10, and 30 microM) decreased, in a concentration-dependent manner, all other membrane currents examined, such as L-type Ca2+ current (ICa), delayed rectifier K+ current (IK), and inward rectifier K+ current (IK1). The Kd (apparent dissociation constant) values were 14.4 microM for ICa, 23.0 microM for IK, and 33.7 microM for IK1 respectively. 3) Cibenzoline (5, 10, and 30 microns) significantly shortened the action potential duration measured at both 30% and 90% repolarization without altering the resting membrane potential. From these findings, we conclude that apart from potent inhibitory effects on INa, cibenzoline possesses multiple blocking effects on other currents, e.g., ICa, IK and IK1, with a different potency (INa > ICa > IK > IK1) and with essentially the same efficacy. These effects may explain, at least in part, the alleged, potent antiarrhythmic effects of this drug.
Action Potentials↗
Methicillin-resistant Staphylococcus aureus colonization in a new nursing home.
Methicillin-resistant Staphylococcus aureus (MRSA) has been detected in nursing homes and long-term care facilities. Studies disagree about the risk of infection with MRSA in colonized patients. MRSA colonization and infection were tracked for one year in all admissions to a 60-bed ward at the Philadelphia VA Nursing Home Care Unit (NHCU) from the time of its opening in June, 1990. Patients and staff were blinded to culture results, and the NHCU followed universal precautions for all patients. Of the first 72 patients, 7 were found to be colonized with MRSA; only one of them was known to have had MRSA prior to NHCU transfer. Three patients died (2 had negative cultures prior to death), and 1 was discharged home. Three patients spontaneously cleared MRSA colonization and lived to the end of the study. Three patients appeared to be colonized by MRSA after admission; subsequent cultures were negative. No patients were infected by MRSA in the NHCU. At the close of the study, one year after the nursing home opened, no patient in the nursing home had a culture positive for MRSA. In conclusion, colonization with MRSA at the time of admission to the nursing home is not uncommon, but patients can spontaneously clear it. Besides, nursing homes that pre-screen only those patients with classic risk factors may be admitting many MRSA-colonized patients. Nonetheless, universal precautions appear to be effective in limiting transmission of MRSA in the nursing home; in this study, MRSA acquisition was sporadic and brief.
Aged↗
Non-subjective cataract analysis and its application in space radiation risk assessment.
Experimental animal studies and human observations suggest that the question is not whether or not prolonged space missions will cause cataracts to appear prematurely in the astronauts, but when and to what degree. Historically the major impediment to radiation cataract follow-up has been the necessarily subjective nature of assessing the degree of lens transparency. This has spurred the development of instruments which produce video images amenable to digital analysis. One such system, the Zeiss Scheimpflug slit lamp measuring system (SLC), was incorporated into our ongoing studies of radiation cataractogenesis. It was found that the Zeiss SLC measuring system has high resolution and permits the acquisition of reproducible images of the anterior segment of the eye. Our results, based on about 650 images of the rats lens, and followed over a period of 91 weeks of radiation cataract development, showed that the integrated optical density (IOD) of the lens correlated well with conventional assessment with the added advantages of objectivity, permanent and transportable records and linearity as cataracts become more severe. This continuous data acquisition, commencing with cataract onset, can proceed through more advanced stages. The SLC exhibits much greater sensitivity reflected in a continuously progressive severity despite the artifactual plateaus in staging which occur using conventional scoring methods. Systems such as the Zeiss SLC should be used to monitor astronauts frequent visits to low earth orbit to obtain a longitudinal data-base on the influence of this activity on the lens.
Animals↗
T cell receptor gene regulation of experimental autoimmune myasthenia gravis.
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Animals↗
The hemispheric cerebrovascular response to hemodilution is attenuated by a focal cryogenic brain injury.
Experimental brain injury attenuates the normal increase in cerebral blood flow (CBF) that accompanies a fall in PaO2, and this may contribute to the well-known detrimental effects of hypoxia following closed head injury. Anemia is also known to adversely affect posttraumatic survival, and it is reasonable to hypothesize that this too may be related to an altered cerebrovascular response. Therefore, to examine this possibility, pentobarbital-anesthetized rabbits were subjected to a left posterior parietal cryogenic cortical injury, followed 90 min later by isovolemic hemodilution with hetastarch. Unlesioned control animals underwent an identical degree of hemodilution. CBF was measured using radioactive microspheres. In control animals, hemodilution was accompanied by a marked increase in CBF in all brain regions. For example, in the left posterior cortex, CBF increased from 30 +/- 14 mL/100 g/min (baseline Hct = 42 +/- 2%, mean +/- SD) to 100 +/- 20 mL/100 g/min at Hct = 12 +/- 1%. By contrast, there was a markedly attenuated response throughout the left (ipsilateral) hemisphere of injured animals, even in cortical regions distant from the injury. For example, in the left posterior cortex, CBF changed from a baseline of 32 +/- 21 mL/100 g/min (baseline) to 40 +/- 14 mL/100 g/min at the lowest Hct. CBF responses to hemodilution were unaltered in the contralateral hemisphere and in the hindbrain. These data indicate that a localized brain lesion can produce widespread ipsilateral alterations in the CBF response to hemodilution, with resultant compromise in cerebral O2 delivery. These data support the argument that the CBF increase produced by hemodilution is an active vasodilatory process rather than a passive response to changing blood viscosity.
Animals↗
The dose-related effects of nitric oxide synthase inhibition on cerebral blood flow during isoflurane and pentobarbital anesthesia.
BACKGROUND: Recent work in animals suggests that nitric oxide may play a role in the cerebral blood flow (CBF) changes produced by anesthetics, particularly the vasodilation seen with volatile anesthetics. It is not clear, however, whether nitric oxide causes the flow increase or simply plays some constitutive role. To distinguish between these possibilities, we studied the dose-related effects of nitric oxide synthase inhibition in rabbits with varying baseline CBFs, produced by anesthesia with isoflurane, low-dose pentobarbital, or high-dose pentobarbital. METHODS: New Zealand White rabbits were anesthetized with 1 MAC isoflurane, low-dose pentobarbital (50-mg/kg load, 7.5-mg.kg-1.h-1 infusion), or high-dose pentobarbital (50-mg/kg load, 20-mg.kg-1.h-1, deep burst-suppression on the electroencephalogram), and prepared for the measurement of CBF using radioactive microspheres. The confluence of sinuses was also exposed to permit sampling of cerebral venous blood and the determination of cerebral metabolic rate for O2 (CMRO2). Normocapnia and normothermia were maintained throughout. After baseline measurements, animals were sequentially given a cumulative total of 3, 13, and 43 mg/kg intravenous N omega-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase. CBF and CMRO2 were recorded approximately 10 min after each dose. RESULTS: L-NAME produced a dose-related reduction in CBF in all three anesthetic groups. Statistical examination indicated that the dose response curves were parallel. For example, in isoflurane-anesthetized rabbits, CBF decreased from 77 +/- 19 to 47 +/- 11 ml.100 g-1.min-1 after the 43 mg/kg L-NAME, whereas in high-dose pentobarbital animals, CBF decreased from 42 +/- 15 to 26 +/- 8 ml.100 g-1.min-1 (all values mean +/- SD). Decreases in CMRO2 did not quite achieve significance (P = 0.08), and the CBF/CMRO2 ratio decreased in all animals, suggesting that the CBF reductions were due primarily to direct vasoconstriction. There were no electroencephalographic changes. In separate groups of isoflurane-anesthetized rabbits given 3 mg/kg L-NAME, treatment with 300 mg/kg L-arginine partially reversed the decreases in CBF. By contrast, the effects of 43 mg/kg L-NAME were not reversible with 430 mg/kg L-arginine. CONCLUSIONS: Although L-NAME reduced CBF in all three anesthetic conditions, it did not alter the relative differences among them: CBF in the presence of isoflurane remained much higher than that seen with the barbiturates. This suggests that nitric oxide may not the primary mediator of anesthetic CBF effects, but rather acts to influence background vascular tone in these anesthetized animals.
Amino Acid Oxidoreductases↗
Isolation and characterization of point mutations in the Escherichia coli grpE heat shock gene.
The Escherichia coli grpE gene (along with dnaK, dnaJ, groEL, and groES) was originally identified as one of the host factors required for phage lambda growth. The classical grpE280 mutation was the only grpE mutation that resulted from the initial screen and shown to specifically block the initiation of lambda DNA replication. Here we report the isolation of several new grpE missense mutations, again using phage lambda resistance as a selection. All mutants fall into two groups based on their temperature-dependent phenotype for lambda growth. Members of the first group (I), including grpE17 and grpE280, which was obtained again, are resistant to lambda growth at both 30 and 42 degrees C. Members of the second group (II), including grpE25, grpE66, grpE103, grpE13a, grpE57b, and grpE61, are sensitive to lambda growth at 30 degrees C but resistant at 42 degrees C. All mutations are recessive, since an E. coli grpE null mutant strain carrying these mutant alleles on low-copy-number plasmids are sensitive to infection by the lambda grpE+ transducing phage. Both group I and group II mutants are temperature sensitive for E. coli growth above 42 degrees C. The nucleotide changes were identified by sequencing analyses and shown to be dispersed throughout the latter 75% of the grpE coding region. Most of the amino acid changes occur at conserved residues, as judged by sequence comparisons between E. coli and other bacterial and yeast GrpE homologs. The isolation of these new mutations is the first step toward a structure-function analysis of the GrpE protein.
Amino Acid Sequence↗
Cerebral blood flow and oxygen delivery during hypoxemia and hemodilution: role of arterial oxygen content.
To determine the role of arterial O2 content (CaO2) in the cerebral blood flow (CBF) responses to hypoxemia and hemodilution, CaO2 was progressively reduced from approximately 18 to approximately 6 ml O2/dl in normocapnic, normothermic, pentobarbital-anesthetized rabbits. This was done either by reducing PaO2 (hypoxemia, minimum PaO2 approximately 26 mmHg) or arterial hematocrit (isovolemic hemodilution with hetastarch, minimum hematocrit approximately 14%) while CBF was measured with radioactive microspheres. As CaO2 decreased, CBF increased in both groups but was greater in hypoxemic animals at CaO2 values < or = 9 ml O2/dl. For example, at a CaO2 approximately 6 ml O2/dl, CBF in hypoxemic animals was 110 +/- 38 ml.100 g-1.min-1 (means +/- SD) compared with 82 +/- 22 ml.100 g-1.min-1 in hemodiluted animals (means +/- SD). While calculated cerebral O2 delivery (cerebral DO2) was well maintained in hypoxemic animals, it decreased significantly during hemodilution (from 7.95 +/- 2.92 baseline to 5.08 +/- 1.10 ml O2/dl.100 g-1.min-1 at the lowest CaO2 value). This decrease in cerebral DO2 was offset by an increase in oxygen extraction ratio during hemodilution. By contrast, the small increase in oxygen extraction ratio seen with hypoxemia did not achieve significance. These results suggest that there are different adaptive responses to acute hypoxemia or hemodilution . They also imply that at similar CBF and CaO2 values, tissue O2 availability may be greater during hemodilution than during hypoxemia.
Analysis of Variance↗
[Effect of acupuncture on interleukin-2 level and NK cell immunoactivity of peripheral blood of malignant tumor patients].
This paper deals with the observation of acupuncture therapy affecting interleukin-2(IL-2 level and natural killer (NK) cell immunoactivity in the peripheral blood of patients with malignant tumors. In this clinical-laboratory test research, randomized double blind method was used. The patients were divided into an acupuncture treated group (n = 25) and a control group (n = 20). The former group was treated using points, ST36,LI11,RN6 and locations of symptomatic points bilaterally. They received one treatment of 30 minutes daily for 10 days. The results showed that the IL-2 level and NK cell activity were lower than normal in patients with malignant tumor, but there was an increase in the acupuncture group after 10 days of treatment. Significance was found to be remarkable (P < 0.01). The difference between the two groups was also significant (P < 0.01). This increase might be related to the mechanism of acupuncture that adjusting the body's immune function. Thus, acupuncture therapy could enhance the cellular immune function of patients with malignant tumors and providing a beneficial effect in anti-cancer treatment.
Acupuncture Therapy↗
CBF mediates adenovirus Ela trans-activation by interaction at the C-terminal promoter targeting domain of conserved region 3.
Genetic and biochemical evidence suggest that conserved region 3 (CR3) of the adenovirus Ela polypeptide can provide two distinct and separable functions: an N-terminal transcriptional activation region and a C-terminal promoter targeting region. It is thought that the promoter targeting region of Ela CR3 interacts with promoter-specific transcription factors, thereby bringing the activation region of Ela CR3 in proximity of the promoter. Here we report that CBF, a CCAAT-box-binding factor that regulates hsp70 gene expression and mediates Ela trans-activation in vivo, interacts with the promoter targeting region of Ela CR3 in vitro. Point mutations in Ela CR3 that are defective in stimulating transcription from the hsp70 promoter are also defective in stimulating transcription directed by a synthetic activator, GAL-CBF, composed of the DNA-binding domain of yeast GAL4 fused to CBF. These mutations fall into two classes with respect to their abilities to interact with CBF in vitro. Mutations in the transcriptional activation region of Ela CR3 do not affect binding to CBF, but mutation of the promoter targeting region of Ela CR3 prevents association with CBF in vitro.
Adenovirus E1A Proteins↗
A case-control epidemiologic study of endometriosis.
A case-control study involving 203 cases of pelvic endometriosis seen from 1987-1989, and 406 randomly selected and age-matched community controls was conducted in order to provide information relevant to effective prophylaxis of the disease. The diagnosis was confirmed by pathology from laparotomy and/or laparoscopy. A questionnaire focused on menstrual, marital and reproductive status, professional exposure and physical activities, and the results were analyzed by a conditional logistic regression model. Women characterized by earlier menarche (< or = 12 years) and longer period (> or = 8 days) were found to be associated with an elevated incurring risk, and a trend of increasing risk associated with primary dysmenorrhea (RR = 2.1 for mild to moderate and RR = 5.2 for severe dysmenorrhea), energetic physical activity during menstruation (RR = 2.1), and allergic diathesis (RR = 1.8) was seen. An inverse relationship was observed between the number of pregnancies and risk of endometriosis, and the protective effect was most significant when only the number of full-term pregnancies was counted. The risk factors of endometriosis are discussed, and intensive treatment of primary dysmenorrhea and avoidance of strenuous exercise during menstruation are identified as important measures in the prevention of endometriosis.
Adult↗
Phonon sidebands of excitons bound to isoelectronic impurities in semiconductors.
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Journal Article↗
Regulation of the human hsp70 promoter by p53.
The tumor suppressor p53 is a nuclear phosphoprotein with characteristics of a transcription factor. It displays sequence-specific DNA binding, contains a potent transactivation domain, and has been implicated as both a transcriptional activator and a repressor. Transcription of the human hsp70 gene is stimulated by adenovirus E1a protein. This E1a transactivation of the hsp70 promoter is mediated by CCAAT binding factor (CBF). It is demonstrated here that p53 both represses transcription from the human hsp70 promoter and also interacts with CBF. Thus, the repression of the hsp70 promoter by p53 may be mediated by direct protein-protein interaction with CBF. These results suggest that protein-protein interaction between p53 and specific transcription factors may be an additional mechanism by which p53 regulates gene expression.
Adenovirus E1A Proteins↗
Antitumor effect of interleukin 7 in combination with local hyperthermia in mice bearing B16a melanoma cells.
Interleukin (IL)-7 has been evaluated for its influence, alone or in combination with local hyperthermia (LH), on B16a melanoma-bearing mice. Six- to eight-week-old C57BL/6J male mice were inoculated s.c. with 5 x 10(5) tumor cells into the left hind limb. Mice were randomly divided into four groups, and treated s.c. with IL-7 (5 ng) or saline as control, twice a day for three weeks beginning eight days after tumor inoculation. LH, using hot water circulator at 43 +/- 0.2 degrees C for 30 min, was induced to the limb with tumor twice a week for two weeks. Size of the primary tumor was measured every other day for five weeks. Mice were sacrificed five weeks after tumor inoculation. The size of the primary tumor and the number of lung metastases were reduced in mice treated either with IL-7 or LH alone. As a control for IL-7, granulocyte colony stimulating factor (G-CSF) alone had no effect on primary tumor size or number of lung metastases. The greatest antitumor effect was observed in mice treated with IL-7 in combination with LH. Survival was prolonged significantly only in mice treated with IL-7 plus LH compared with that of mice treated with saline. Decreased natural killer (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/Lyt2+ cells were associated with tumor growth. These parameters were restored in mice treated with IL-7 plus LH. Increases in levels of IL-1 alpha, IL-6, tumor necrosis factor (TNF alpha) and interferon (IFN gamma) were associated with an increase in the survival of tumor-bearing mice treated with IL-7 and/or LH. These results suggest that changes in T-cell, NK cell and cytokines such as IL-1 alpha, IL-6, TNF-alpha and IFN-gamma in response to IL7 and/or LH might account for prolonged survival of B16a melanoma-bearing mice and that IL-7 might be useful as a potential antitumor agent combined with other therapy in certain malignant solid tumors with metastases.
Animals↗
The utility of PRO data on surgical volume: the example of carotid endarterectomy.
As part of a small-area analysis of carotid endarterectomy (CE) surgery, this review of Medicare claims data for a 26-month period addresses variations in surgical volume, mortality, readmissions, and charges. A surprisingly high percentage of surgeons performing CE did few procedures, and surgical volume appeared to be associated with higher mortality and charges. The implications of these data for both hospital credentialing committees and management and for purchasers and consumers of care, as well as the ways in which the Health Care Financing Organization's (HCFA) Health Care Quality Improvement Initiative (HCQII) will reorder their relationships with peer review organizations (PROs), are discussed. This study is useful in addressing the potential of efforts by PROs to increase the quality of care under the HCQII.
Data Collection↗
The effect of age on the synthesis of two heat shock proteins in the hsp70 family.
Hepatocytes isolated from male F344 rats were exposed to elevated temperatures (40 degrees C to 45 degrees C), and the incorporation of [35S]-L-methionine into proteins was measured from fluorograms of two-dimensional polyacrylamide gels. The synthesis of two proteins was induced by temperatures of 40 degrees C to 42.5 degrees C; however, 45 degrees C inhibited the synthesis of all proteins. Based on their apparent molecular weights and pI values and their recognition by a monoclonal antibody to the HSP70 gene family, the two proteins induced by hyperthermia were found to be the highly heat-inducible hsp70 and the constitutive hsc70. Because a heat shock of 42.5 degrees C for 30 minutes had very little effect on cell viability and induced the synthesis of hsp70 and hsc70, this heat shock was used to study the effect of age on the ability of hepatocytes to respond to the stress of hyperthermia. Neither hepatocytes isolated from young adult (5-7 months) nor old (25-27 months) rats synthesized detectable amounts of hsp70 when incubated at 37 degrees C. However, heat shock induced the synthesis of both hsp70 and hsc70 in hepatocytes isolated from young adult and old rats. The induction of hsp70 synthesis was significantly lower (37%) for hepatocytes isolated from old rats compared to hepatocytes isolated from young adult rats. However, neither the basal level nor the induced level of hsc70 synthesis changed significantly with age. Thus, aging resulted in a decrease in the ability of hepatocytes to synthesize hsp70 in response to hyperthermia; this effect, however, was specific for hsp70.
Actins↗
Cibenzoline inhibits diazoxide- and 2,4-dinitrophenol-activated ATP-sensitive K+ channels in guinea-pig ventricular cells.
1. We have investigated the effects of diazoxide (a sulphonamide derivative) and cibenzoline (a class I antiarrhythmic drug) on ATP-sensitive K+ currents in guinea-pig ventricular cells, using whole-cell clamp techniques. 2. Diazoxide (50 microM) produced a marked shortening of action potential duration which was antagonized by 1 microM glibenclamide, an ATP-sensitive K+ channel blocker. 3. Diazoxide (50 microM) increased the quasi-steady state outward current elicited by a ramp voltage protocol (-20 mV s-1) at potentials positive to about -70 mV. This effect was completely prevented in the presence of glibenclamide (1 microM), thereby suggesting that diazoxide opens ATP-sensitive K+ channels. 4. Cibenzoline (5 microM) depressed the diazoxide-induced increases in the outward current and the pretreatment with this agent prevented the development of the diazoxide-induced outward current. 5. Cibenzoline (10 microM) reversed the 2,4-dinitrophenol (50 microM)-induced shortening of the action potential duration partially but significantly. 6. These results suggest that diazoxide activates ATP-sensitive K+ channels of guinea-pig ventricular cells and that cibenzoline, at therapeutic concentrations, inhibits this channel.
2,4-Dinitrophenol↗