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Biomedical subjects

E Lee

Publications and source records attributed to E Lee.

At least 181 records · Page 10Linked to original sources

Prolonged hormone secretion from neuroendocrine cells of Aplysia is independent of extracellular calcium.

The role of Ca2+ from extracellular and intracellular sources in stimulating neurosecretion was investigated in four experiments using neuroendocrine bag cells of the marine mollusk Aplysia. (i) Bag cells were treated with either an extracellular calcium chelator (BAPTA) or Co(2+)-substitution within 30 s after onset of an electrical afterdischarge to prevent influx of Ca2+ from extracellular fluid. These treatments shortened the duration of the afterdischarge, but did not significantly affect the overall pattern or total amount of egg laying hormone (ELH) secretion, suggesting that extracellular Ca2+ is not required for maintenance of ELH release. (ii) Substitution of Ba2+ for Ca2+ has previously been shown to support bag cell afterdischarges that trigger transient elevations in intracellular Ca2+. We showed that this treatment also stimulates ELH secretion, suggesting that Ca2+ release from intracellular stores can stimulate ELH secretion. (iii) To raise intracellular Ca2+ levels in the absence of an afterdischarge, the calcium ionophore X537A was used to transport Ca2+ across plasma and organelle membranes. When this treatment was combined with extracellular calcium chelators so that the only source of Ca2+ was from intracellular compartments, ELH secretion was stimulated. Taken together, these findings are consistent with the hypothesis that release of Ca2+ from intracellular stores is sufficient to stimulate ELH secretion.

Animals↗

Key indicators for the monitoring and evaluation of control programmes of human African trypanosomiasis due to Trypanosoma brucei gambiense.

Very little research has been devoted to the design of epidemiological tools for the monitoring and evaluation of National Human African Trypanosomiasis (HAT) Control Programmes and daily management decisions are made in the absence of accurate knowledge of the situation. This paper identifies key indicators necessary to make decisions in the field and constantly adjust control activities to changing situations. Examples are derived from the Médecins Sans Frontières (MSF) HAT Control Programme in Adjumani, Uganda. Based on the principles of quality assurance, the focus is placed on process indicators. A conceptual framework derived from a system view/planning cycle perspective is also described for the construction of indicators. Finally, some specific challenging aspects of the epidemiology of HAT are presented and the limitations of the interpretation of the indicators discussed.

Animals↗

A randomized, prospective, comparative study of manual and automated renal biopsies.

A percutaneous renal biopsy can be performed in several ways, including using a spring-loaded biopsy gun. As this form of renal biopsy has become more popular, a controversy has developed regarding tissue adequacy and the incidence of complications. To compare these two aspects in an automated biopsy and a manual biopsy, we studied 166 patients assigned to one of the two renal biopsy methods. In a randomized, prospective manner from June 1994 until February 1997, group 1 (67 patients) received a 14 G Tru-cut needle (Baxter, Deerfield, IL) manual biopsy while group 2 (99 patients) received an 18 G automated gun biopsy. There was no difference in sex, age, hemoglobin level, prothrombin time, partial thromboplastin time, or diastolic and systolic blood pressure prebiopsy in groups I and II. Indications for biopsy were proteinuria (38%), proteinuria accompanied by hematuria (31.3%), acute renal failure (9.6%), lupus nephropathy (9.6%), chronic renal failure (6%), and hematuria only (5.4%). In group I, the number of cores was 1.88 +/- 0.56, the glomeruli obtained were 27.3 +/- 13.8, and the number of glomeruli per core were 15.3 +/- 8.4. In group II, the values were 2.37 +/- 0.88, 20.7 +/- 11.1, and 9.95 +/- 6.9, respectively. These results showed a statistically significant difference (P < 0.05). In all cases, pathological diagnosis was possible. The histology showed IgA nephropathy in 25.9%, minimal change disease in 16.3%, lupus nephritis in 11.4%, membranous glomerulonephropathy in 9.3%, membranoproliferative glomerulonephritis in 5.4%, and others. The incidence of postbiopsy hematoma was marginally greater in group I (22.3% v 11.1%) and the area of perirenal hematoma shown on ultrasound 24 hours postbiopsy was larger in group I, as well (848 +/- 623 mm2 v 338 +/- 260 mm2). Hematocrit levels before and after biopsy showed a significant difference (34.9% +/- 7.9% and 34.0% +/- 7.6%, respectively; P < 0.05) in group I, but no significant difference was observed in group II (35.1% +/- 7.0% and 34.7% +/- 6.9%). Both techniques rendered adequate tissue sampling, but the extent of bleeding was more severe with the manual 14 G Tru-cut needle biopsy.

Acute Kidney Injury↗

Effect of beta-adrenergic agents on intracellular potential of rabbit ciliary epithelium.

PURPOSE: To study the effects of beta-adrenergic agents on intracellular potential (Vm) of the isolated and intact rabbit ciliary epithelium. METHODS: Vm was measured on the isolated intact ciliary epithelium superfused with adrenergic agents and cyclic AMP modulators. RESULTS: The nonselective beta-adrenergic agonist isoproterenol depolarized Vm in a dose-dependent fashion. beta-adrenergic antagonists alone had no effect on baseline Vm. The isoproterenol response was blocked by the nonselective antagonist timolol (5 x 10(-5) M). The selective beta 2-antagonist ICI 118-551 caused a greater inhibition (IC50 approximately 7 x 10(-7)) than the selective beta 1-antagonist betaxolol (IC50 approximately 6 x 10(-6)). The isoproterenol response was also significantly (p < 0.03) blocked by the non-selective alpha-antagonist phentolamine. Cyclic AMP and phosphodiesterase inhibitors significantly decreased Vm. Pretreatment with these inhibitors potentiated the agonist-induced depolarization. Barium, a blocker of Ca(2+)-sensitive K+ channels, significantly decreased baseline Vm. Barium pretreatment blocked the beta-agonist and cAMP induced depolarization of Vm, suggesting that the K+ current is necessary for the observed isoproterenol response. Pretreatment with the cotransport inhibitor bumetanide had no effect on the isoproterenol-induced response. CONCLUSIONS: The beta-adrenergic agonist isoproterenol affects ionic transport processes across the ciliary epithelium (beta 2 > beta 1). This effect is likely mediated through adenylate cyclase coupled to adrenoreceptors and requires the presence of the K+ current. Blockage of the isoproterenol-induced decrease in Vm by a nonselective alpha-adrenergic antagonist indicates an interaction between the two adrenergic systems in the ciliary epithelium.

Adenylyl Cyclases↗

Overexpression of a novel rho family GTPase, RacC, induces unusual actin-based structures and positively affects phagocytosis in Dictyostelium discoideum.

Rho family proteins have been implicated in regulating various cellular processes, including actin cytoskeleton organization, endocytosis, cell cycle, and gene expression. In this study, we analyzed the function of a novel Dictyostelium discoideum Rho family protein (RacC). A cell line was generated that conditionally overexpressed wild-type RacC three- to fourfold relative to endogenous RacC. Light and scanning electron microscopy indicated that the morphology of the RacC-overexpressing cells [RacC WT(+) cells] was significantly altered compared with control cells. In contrast to the cortical F-actin distribution normally observed, RacC WT(+) cells displayed unusual dorsal and peripheral F-actin-rich surface blebs (petalopodia, for flower-like). Furthermore, phagocytosis in the RacC WT(+) cells was induced threefold relative to control Ax2 cells, whereas fluid-phase pinocytosis was reduced threefold, primarily as the result of an inhibition of macropinocytosis. Efflux of fluid-phase markers was also reduced in the RacC WT(+) cells, suggesting that RacC may regulate postinternalization steps along the endolysosomal pathway. Treatment of cells with Wortmannin and LY294002 (phosphatidylinositol 3-kinase inhibitors) prevented the RacC-induced morphological changes but did not affect phagocytosis, suggesting that petalopodia are probably not required for RacC-induced phagocytosis. In contrast, inactivating diacylglycerol-binding motif-containing proteins by treating cells with the drug calphostin C completely inhibited phagocytosis in control and RacC WT(+) cells. These results suggest that RacC plays a role in actin cytoskeleton organization and phagocytosis in Dictyostelium.

Androstadienes↗

Suppression of mouse skin tumor promotion and induction of apoptosis in HL-60 cells by Alpinia oxyphylla Miquel (Zingiberaceae).

There have been considerable efforts to search for naturally occurring substances for the intervention of carcinogenesis. Many components from dietary or medicinal plants have been identified that possess substantial chemopreventive properties. An example is curcumin (Curcuma longa Linn., Zingiberaceae), which has been shown to inhibit tumor promotion in experimental carcinogenesis. Alpinia oxyphylla Miquel, another plant of the ginger family used in oriental herbal medicine, contains diarylheptanoids whose structures are analogous to that of curcumin. In the present study, we have tested A.oxyphylla for its ability to suppress tumor promotion. Thus, topical application of the methanolic extract of dried fruits of A.oxyphylla significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumor promotion as well as ear edema in female ICR mice. In another study, treatment of HL-60 cells with the methanolic extract of A.oxyphylla significantly reduced the viability of the cells and also inhibited DNA synthesis. Microscopic examination of the treated cells showed characteristic morphology of apoptosis. Furthermore, cells treated with the extract of A.oxyphylla exhibited internucleosomal DNA fragmentation in time- and concentration-dependent manners. TPA-stimulated generation of superoxide anion in differentiated HL-60 cells was also blunted by A.oxyphylla. Taken together, these findings suggest that A.oxyphylla possesses potential chemopreventive and antitumorigenic activities.

9,10-Dimethyl-1,2-benzanthracene↗

Income, language, and citizenship status: factors affecting the health care access and utilization of Chinese Americans.

This article reports the results of a randomly administered interview of 1,808 Chinese American residents of San Francisco. The study examines income, language, and citizenship status and their effect on the use of health care services by this population. The articles discusses the implications of the findings for low-income and uninsured individuals, particularly people of immigrant status, and concludes with suggestions for local health care planners and advocates.

Adult↗

Genetic manipulation of alcohol dehydrogenase levels in ripening tomato fruit affects the balance of some flavor aldehydes and alcohols

Tomato (Lycopersicon esculentum) plants were transformed with gene constructs containing a tomato alcohol dehydrogenase (ADH) cDNA (ADH 2) coupled in a sense orientation with either the constitutive cauliflower mosaic virus 35S promoter or the fruit-specific tomato polygalacturonase promoter. Ripening fruit from plants transformed with the constitutively expressed transgene(s) had a range of ADH activities; some plants had no detectable activity, whereas others had significantly higher ADH activity, up to twice that of controls. Transformed plants with fruit-specific expression of the transgene(s) also displayed a range of enhanced ADH activities in the ripening fruit, but no suppression was observed. Modified ADH levels in the ripening fruit influenced the balance between some of the aldehydes and the corresponding alcohols associated with flavor production. Hexanol and Z-3-hexenol levels were increased in fruit with increased ADH activity and reduced in fruit with low ADH activity. Concentrations of the respective aldehydes were generally unaltered. The phenotypes of modified fruit ADH activity and volatile abundance were transmitted to second-generation plants in accordance with the patterns of inheritance of the transgenes. In a preliminary taste trial, fruit with elevated ADH activity and higher levels of alcohols were identified as having a more intense "ripe fruit" flavor.

Journal Article↗

Novel binding sites for regulatory factors in the human papillomavirus type 18 enhancer and promoter identified by in vivo footprinting.

The E6 and E7 genes of human papillomaviruses (HPVs) associated with anogenital cancers are largely responsible for the oncogenic activity of these viruses, and regulation of these genes has been intensively studied. Transcription of the E6 and E7 genes is controlled by the viral upstream regulatory region (URR). We have used in vivo footprinting to examine the occupancy by regulatory factors of the HPV type 18 (HPV18) URR enhancer and promoter in the cervical carcinoma cell lines HeLa and C4-II. While corroborating occupancy in vivo of all of the elements previously implicated in the transcriptional control of the HPV18 E6 and E7 genes by in vitro DNase I footprinting, gel retardation assays, and transfection studies, we also detect occupancy in vivo of several enhancer and promoter sequences which have not been previously identified as HPV18 URR regulatory elements. Our data suggest that the HPV18 enhancer and promoter are more densely occupied by DNA-binding proteins than previously thought and raise the possibility that additional, possibly novel factors contribute to transcription of the HPV18 early genes.

Base Sequence↗

Podokinesis in endothelial cell migration: role of nitric oxide.

Previously, we demonstrated the role of nitric oxide (NO) in transforming epithelial cells from a stationary to locomoting phenotype [E. Noiri, T. Peresleni, N. Srivastava, P. Weber, W.F. Bahou, N. Peunova, and M. S. Goligorsky. Am. J. Physiol. 270 (Cell Physiol. 39): C794-C802, 1996] and its permissive function in endothelin-1-stimulated endothelial cell migration (E. Noiri, Y. Hu, W. F. Bahou; C. Keese, I. Giaever, and M. S. Goligorsky, J. Biol: Chem. 272: 1747-1753, 1997). In the present study, the role of functional NO synthase in executing the vascular endothelial growth factor (VEGF)-guided program of endothelial cell migration and angiogenesis was studied in two independent experimental settings. First, VEGF, shown to stimulate NO release from simian virus 40-immortalized microvascular endothelial cells, induced endothelial cell transwell migration, whereas NG-nitro-L-arginine methyl ester (L-NAME) or antisense oligonucleotides to endothelial NO synthase suppressed this effect of VEGF. Second, in a series of experiments on endothelial cell wound healing, the rate of VEGF-stimulated cell migration was significantly blunted by the inhibition of NO synthesis. To gain insight into the possible mode of NO action, we next addressed the possibility that NO modulates cell matrix adhesion by performing impedance analysis of endothelial cell monolayers subjected to NO. The data showed the presence of spontaneous fluctuations of the resistance in ostensibly stationary endothelial cells. Spontaneous oscillations were induced by NO, which also inhibited cell matrix adhesion. This process we propose to term "podokinesis" to emphasize a scalar from of micromotion that, in the presence of guidance cues, e.g., VEGF, is transformed to a vectorial movement. In conclusion, execution of the program for directional endothelial cell migration requires two coexisting messages: NO-induced podokinesis (scalar motion) and guidance cues, e.g., VEGF, which imparts a vectorial component to the movement. Such a requirement for the dual signaling may explain a mismatch in the demand and supply with newly formed vessels in different pathological states accompanied by the inhibition of NO synthase.

Animals↗

Effects of Helicobacter pylori gastritis on gastric secretion in healthy human beings.

Helicobacter pylori gastritis is common, but effects on gastric secretion are not well understood. We measured basal and pentagastrin-stimulated gastric acidity, pepsin activity, and fluid output, as well as serum gastrin concentrations and H. pylori antibody levels, before and after treatment of H. pylori gastritis in 28 men and women. Subjects were studied before and 1 and 3 mo after a course of bismuth, metronidazole, and tetracycline. Elimination of H. pylori gastritis, accomplished in 14 subjects, increased basal and pentagastrin-stimulated gastric acidity (by 15 meq/l) and basal acid output significantly (by 2.1 meq/h 1 mo after therapy). Elimination of H. pylori had an opposite effect on pepsin secretion, significantly decreasing pepsin output by 30%. Elimination of H. pylori significantly reduced nonparietal fluid output by 35%, without affecting fluid output from parietal cells. Serum gastrin and H. pylori antibody levels declined significantly after elimination of H. pylori. None of these changes was observed in 14 subjects whose H. pylori gastritis was resistant to antimicrobial therapy. In summary, eradication of H. pylori infection increases gastric acidity by reducing nonparietal gastric secretion from peptic and other cells.

Adult↗

Prevalence of lower urinary tract symptoms in Korean men in a community-based study.

OBJECTIVE: The prevalence of lower urinary tract symptoms was determined in Korean men aged 50 and over. METHODS: A community-based, epidemiologic study was performed in Yonchon County, Korea. The Korean version of the International Prostate Symptom Score (I-PSS) was used to assess the severity of urinary symptoms in a representative sample of 514 men. RESULTS: Nocturia and weak stream were the most prevalent symptoms and urgency was the least. Overall, 23.2% of the men were moderately to severely symptomatic: 17.7% in the age group of 50-59 years, 23.3% in that of 60-69 years and 35.3% in that of 70 years and over. The proportion of severely symptomatic men approximately doubled with each decade of age. The 'quality of life' score showed a high correlation with the I-PSS. Our estimation indicated that in 1995 approximately 800,000 Korean men had moderate to severe lower urinary tract symptoms that were likely to be associated with benign prostatic hyperplasia. CONCLUSIONS: The prevalence of moderate to severe lower urinary tract symptoms in Korean men is substantially similar to that in Caucasians.

Aged↗

Human ZP3 restores fertility in Zp3 null mice without affecting order-specific sperm binding.

The mammalian zona pellucida surrounding ovulated eggs mediates sperm binding at fertilization, provides a postfertilization block to polyspermy, and facilitates passage of pre-implantation embryos down the oviduct. Although the three zona proteins (ZP1, ZP2, ZP3) are well conserved, mammalian fertilization is relatively specific and human sperm do not bind to the mouse zona pellucida. There are considerable in vitro data that ZP3 acts as a primary sperm adhesion molecule in mice and, by analogy, a similar role has been postulated for human ZP3. Genetically altered mice lacking ZP3 (Zp3(tm/tm)) do not form a zona pellucida and are infertile. To rescue this phenotype, transgenic mice expressing human ZP3 (67% identical to mouse ZP3) were produced and bred with Zp3(tm/tm) null mice. The resultant human ZP3 rescue females had chimeric zonae pellucidae composed of mouse ZP1, mouse ZP2 and human ZP3. Human ZP3 expressed in mouse oocytes had an apparent mass (64 kDa) indistinguishable from native human ZP3 and distinct from mouse ZP3 (83 kDa). Despite the presence of human ZP3, human sperm did not bind to the chimeric zona pellucida, and notwithstanding the absence of mouse ZP3, mouse sperm bound to ovulated eggs in vitro and fertility was restored in vivo. These data have implications regarding the molecular basis of mouse and human sperm binding to their respective zonae pellucidae.

Animals↗

[Apoptosis of astroglial cells].

Astrocytes, the most abundant glial cell type in the brain, are considered to have physiological and pathological roles in neuronal activities. We found that reperfusion of cultured astrocytes after Ca2+ depletion causes delayed cell death and that the Na(+)-Ca2+ exchanger in the reverse mode is responsible for this Ca(2+)-mediated cell injury (Ca2+ paradox injury). The Ca2+ paradox injury of cultured astrocytes is considered to be an in vitro model of ischemia/reperfusion injury, since a similar paradoxical change in extracellular Ca2+ concentration is reported in ischemic brain tissue. Furthermore, we demonstrated that heat shock proteins, glutathione and calcineurin inhibitors protected astrocytes against Ca2+ paradox-induced cell toxicity. We also observed DNA fragmentation, a typical apoptotic ladder, 2-3 days after hydrogen peroxide exposure. In addition, laser microscopic observation showed that reperfusion after the exposure to hydrogen peroxide caused nuclear condensation of astrocytes. Hydrogen peroxide-induced cell injury and DNA fragmentation were attenuated by the NF-kappa B inhibitor ammonium pyrrolidinedithiocarbamate, 1,10-phenanthroline and a caspase 3 inhibitor. These findings suggest that astrocytes are one of the targets for ROS and the oxidative stress-induced delayed death of astrocytes is at least due to apoptosis.

Animals↗

Cerebral vasoreactivity by transcranial Doppler in carbon disulfide poisoning cases in Korea.

The abnormalities of cerebral vasoreactivity were evaluated in CS2 poisoning cases. In 34 retired workers with CS2 poisoning (case group) and 20 healthy individuals (control group), blood flow velocities were measured in the middle cerebral arteries (MCA) by transcranial Doppler. Compared with the control group, the case group showed lower mean values of blood flow velocities and pulsatile indices. The differences in CO2 reactivities of both groups were remarkable (1.10-2.19% decrease/mmHg CO2 for cases and 3.35-5.08 for controls). Multiple regression analyses were conducted to adjust the effect of age, sex, and exposure level (non-low-high exposure) to CO2 reactivity and pulsatile index. The exposure level was statistically significant in the regression model for CO2 reactivity of both MCA and for pulsatile index of the right MCA. Our study noted a decrease of CO2 reactivity and pulsatile index of cerebral vessels related with CS2 exposure. These findings suggested that CS2 exposure could lead to a decrease of cerebral vasoreactivities by the atherosclerotic change of cerebral vessels.

Adult↗

Removal of methylene blue from plasma via an adsorbent filter.

OBJECTIVE: To evaluate adsorbent filtration of methylene blue (MB) and leukocytes from plasma. METHODS: Plasma (750 ml) from apheresis of 10 normal subjects was split into three aliquots: control (A), filtration (B) and MB addition (to 1 microM), phototreatment and filtration (C). Biochemical and coagulation tests were performed: units A and B were reinfused. RESULTS: Filtration reduced MB to undetectable (< 0.05 microM) levels and leukocytes by 3 log10. Biochemical analytes were unchanged. The partial thromboplastin time was prolonged with MB addition (11 +/- 13%) or filtration (26 +/- 12%, p < 0.05), but the effects were not additive. Autologous transfusion was well tolerated. CONCLUSION: Adsorbent filtration can reduce residual MB to undetectable levels and yields a component suitable for transfusion.

Adsorption↗