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Biomedical subjects

K Wu

Publications and source records attributed to K Wu.

At least 127 records · Page 7Linked to original sources

[A pilot study on malaria control by using a new strategy of combining strengthening infection source treatment and health education in mountainous areas of Hainan province].

AIM: To explore a new malaria control strategy that fits current epiodemiological condition and coincides with modern medicine model and the principle of cost-benefit. METHODS: The new strategy highlights the risk villages and risk population as the focal point and integrates health education with behavioral intervention. The main anti-malaria measures consists of carrying out health education in risk villages, giving mass drug administrations in risk population staying overnight in the mountain, following up malaria cases for implementing radical cure, but without using traditional residual spraying or impregnating bednets with insecticides. RESULTS: After having adopted the new strategy and taken the control measures, the people's knowledge about malaria increased to a higher level and the indices of malaria reduced to a lower level. The rate of bednet-using in the population was increased from 26.8% to 72.6%. The annual parasite incidence (API) of malaria was declined from 3.5% in 1994 to 1.1% in 1996 and 0.8% in 1997, and the API of falciparum malaria was declined from 1.0% to 0.3% and 0.3% respectively in the townships at the same time. The parasite rate(PR) of malaria was declined from 7.2% in May, 1995 to 2.1% in November, 1996 and 1.2% in October, 1997 and the PR of falciparum malaria was declined from 1.2% in May, 1995 to 0.1% in October, 1997. The proportion of villages without malaria cases was increased from 18.6% in 1994 to 54.2% in 1997, and the number of risk villages with a malaria incidence above 5% was reduced from 14 to 2 at the same time. The ratio of cost/benefit was 1:2.4 in 1995-1996 and 1:4.4 in 1997, showing a better economic benefit. CONCLUSION: The expectant result has been obtained, thereby providing new experience for the malaria control in the mountainous areas of Hainan Province.

China↗

Keratinocyte growth factor down-regulates expression of the sucrase-isomaltase gene in Caco-2 intestinal epithelial cells.

The molecular mechanisms that regulate the proliferation and differentiation of intestinal mucosal epithelial cells are not well understood. Keratinocyte growth factor (KGF) is an epithelial cell-specific growth factor that may be involved in the maintenance of mucosal epithelial populations and in mediating epithelial repair after injury. The sucrase-isomaltase (SI) gene, which encodes an enterocyte brush border disaccharidase, has served as a model for study of intestinal-specific gene expression and differentiation. KGF down-regulated SI mRNA and protein expression in Caco-2 intestinal epithelial cells but not the expression of other brush border enzymes. The down-regulation was dose- and time-dependent and specifically blocked by anti-KGF antibodies. Transfection experiments using SI promoter constructs demonstrated that KGF decreased SI gene transcription. In contrast, the stability of SI mRNA was not affected by incubation of Caco-2 cells with KGF. Electrophoretic mobility shift analysis demonstrated that binding of nuclear proteins to the SI footprint (SIF) 3 and SIF4 regulatory elements within the SI promoter region was increased in Caco-2 cells that had been incubated with KGF. In transfection experiments using a construct in which tandem copies of the SIF4-binding site were inserted upstream of the SV40 promoter and luciferase gene, incubation with KGF resulted in a significant decrease in luciferase activity. However, transfection with a similar construct containing tandem copies of SIF3 had no significant effect on SV40 promoter activity following KGF treatment. SIF4 may bind E4BP4, a previously identified transcriptional repressor protein. This factor may in part mediate the decrease in SI transcription by KGF in Caco-2 cells.

Caco-2 Cells↗

The fall and rise of carotid endarterectomy in the United States and Canada.

BACKGROUND: Randomized clinical trials have demonstrated the efficacy of carotid endarterectomy in the prevention of stroke when the procedure is performed in regional centers of surgical excellence. However, the relative effects of these studies on the rates of carotid endarterectomy in the United States and Canada have been unclear. METHODS: We calculated the annual rate of carotid endarterectomy in the U.S. states of California and New York and in the Canadian province of Ontario from 1983 through 1995. We also studied whether patients in the early 1990s were selectively referred to hospitals with high volumes of procedures and historically low in-hospital mortality rates. RESULTS: Rates of carotid endarterectomy fell in all three regions from 1984 to 1989 (from 126 to 66 per 100,000 adults 40 years of age or older in California, from 65 to 40 per 100,000 in New York, and from 40 to 15 per 100,000 in Ontario), after the publication of studies demonstrating that the rates of complications of carotid endarterectomy were unacceptably high. However, the clinical trials of the 1990s, which showed benefit from carotid endarterectomy, were associated with a dramatic resurgence in the rates of the procedure from 1989 to 1995 (from 66 to 99 per 100,000 in California, from 40 to 96 per 100,000 in New York, and from 15 to 38 per 100,000 in Ontario). These increased rates were not associated with proportionally greater numbers of referrals of patients to hospitals with low mortality rates. CONCLUSIONS: There have been a dramatic fall and rise in the rates of carotid endarterectomy in both the United States and Canada, which correlate with the publication of first unfavorable and then favorable clinical studies. The absence of selective referral of patients to centers with the lowest mortality rates raises questions about whether the benefits of carotid endarterectomy in the general population are similar to those demonstrated in the clinical trials.

Adult↗

NMDA receptor subunits in the postsynaptic density of rat brain: expression and phosphorylation by endogenous protein kinases.

N-methyl-D-aspartate (NMDA) receptors (NRs) play critical roles in diverse synaptic processes in the brain. However, subcellular distribution, spatiotemporal expression and regulation of NR subunits in brain synapses are unknown. We report that NR1 and NR2A-2C subunits are all enriched in the postsynaptic density (PSD), which plays critical roles in trophin-mediated synaptic plasticity. Significant expression of NRs was observed the first two weeks after birth, during synaptogenesis, and in adulthood. Functional diversity of NRs, resulting from heterogeneous composition, was supported by the finding that different NR2 subunits were associated in a region-specific manner with NR1. Phosphorylation of NR1, a key subunit of the NMDA receptor-channel complex, was significantly enhanced by activators of calmodulin (CaM) kinases (CKs) or protein kinase C (PKC), but not by those of PKA. Co-immunoprecipitation studies revealed that NR1 was physically associated with functionally active PKCgamma and the major PSD protein (mPSDp) through noncovalent interactions. Our results suggest that NMDA receptors play roles in postsynaptic mechanisms in a subunit-, composition-, brain region- and developmental-specific manner. Our findings also indicate that the PSD is a coherent functional unit containing protein kinases that potentially regulate NMDA receptor function via phosphorylation.

8-Bromo Cyclic Adenosine Monophosphate↗

The improving outcomes of coronary artery bypass graft surgery in Ontario, 1981 to 1995.

BACKGROUND: There is continuing uncertainty over the relative contribution of outcomes monitoring to changes in surgical outcomes over time. The authors studied temporal trends in the clinical characteristics and short-term outcomes of patients who underwent coronary artery bypass grafting (CABG) in Ontario before and after the implementation, in 1993, of a province-wide program to provide feedback on cardiac surgery outcomes. METHODS: The authors analysed data from hospital discharge abstracts on the clinical characteristics and in-hospital death rates of all 67,784 patients who underwent isolated CABG in Ontario between Apr. 1, 1981, and Mar. 31, 1996. RESULTS: Death rates were relatively stable during the first half of the 1980s, then declined gradually in the second half of the decade; this decline continued into the first half of the 1990s. In the 1990s patients were older than those in the 1980s, and a higher proportion had coexisting diseases. Between 1986/87 and 1995/96 the unadjusted death rate decreased by 52% (5.0% v. 2.4%) (p < 0.001). The annual relative rate of decline was approximately 6% (95% confidence interval 5% to 7%) in the period before the outcomes feedback program was implemented and about 9% (95% confidence interval 7% to 11%) in the period after implementation. INTERPRETATION: Rates of death after CABG have been declining steadily in Ontario since the mid-1980s. Outcomes-based quality improvement interventions may facilitate; but are not a prerequisite for, improvements in the quality of surgical care.

Adult↗

Monosynaptic activation of CA3 by the medial perforant path.

The functional projection of the medial perforant path (MPP) to different CA3 subfields was studied in urethan-anesthetized rats using current source density analysis. MPP stimulation resulted in an early-latency (presumed monosynaptic) sink with onset of 2-3 ms at the distal apical dendritic layer of CA3 (stratum lacunosum molecule) and a long-latency (presumed disynaptic, >7 ms) sink at stratum lucidum and radiatum of CA3. The population spike (onset 5. 3-6.1 ms), a sink at CA3 pyramidal cell layer, was observed 67% of the time (12 of 18 rats) in CA3a, 44% (8 of 18) in CA3b and 58% (7 of 12 rats) in CA3c following MPP stimulation. Population spike was not observed during presumed disynaptic excitation of CA3. Both early-latency sink (excitatory postsynaptic potential) and population spike in CA3 revealed robust paired-pulse facilitation (PPF). In contrast, little PPF was found for the MPP-evoked excitatory sink at the middle molecular layer of the dentate gyrus. The data suggested that the entorhinal cortex provides a strong monosynaptic excitation of different subfields of CA3. A direct entorhinal to CA3 input bypasses the dentate gyrus and may play a role in normal hippocampal signal processing and neural plasticity.

Action Potentials↗

Up-regulation of glucosylceramide synthase expression and activity during human keratinocyte differentiation.

During keratinocyte differentiation, the glycolipid, glucosylceramide (GlcCer), is thought to be synthesized, stored in intracellular lamellar granules and eventually extruded into the intercellular space where GlcCer is hydrolyzed to ceramide, a major component of the epidermal permeability barrier. Previous studies showed that GlcCer synthase (GCS) activity increases during keratinocyte differentiation; however, the mechanism by which GCS activity is regulated was not established. In the present study, we prepared anti-peptide antibodies and amplified cDNA probes based on the cDNA sequence for human GCS (Ichikawa, S., Sakiyama, H., Suzuki, G., Hidari, K. I.-P. J., and Hirabayashi, Y. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 4638-4643) in order to study GCS expression during keratinocyte differentiation. Confluent human keratinocytes in culture were induced to terminally differentiate by elevation of Ca+2 in the medium without exogenous hormones or growth factors. GlcCer synthesis assayed in situ using a fluorescent ceramide analog increased approximately 5-fold during keratinocyte differentiation, peaking at day 6. Fluorescence microscopy studies of living keratinocytes showed that fluorescent ceramide and/or its metabolites accumulated in the Golgi in undifferentiated cells but targeted to unique vesicular structures that may be derived from the trans-Golgi region. Expression of both GCS mRNA, a approximately 3. 8-kilobase transcript on Northern blots, and GCS protein, a approximately 38-kDa polypeptide detected by Western blotting, increased dramatically (approximately 5-fold) during differentiation, reaching a maximum at about day 8. These results suggest that GCS is up-regulated at the transcriptional level during keratinocyte differentiation and provide the first direct evidence for GCS up-regulation in any cell type.

Amino Acid Sequence↗

BDNF acutely increases tyrosine phosphorylation of the NMDA receptor subunit 2B in cortical and hippocampal postsynaptic densities.

While neurotrophins are critical for neuronal survival and differentiation, recent work suggests that they acutely regulate synaptic transmission as well. Brain-derived neurotrophic factor (BDNF) enhances excitatory postsynaptic currents in cultured dissociated hippocampal neurons within 2-3 min through postsynaptic, phosphorylation-dependent mechanisms. Moreover, BDNF modulates hippocampal long-term potentiation, in which postsynaptic NMDA (N-methyl-D-aspartate) receptors (NRs) play a key role. We now report that BDNF acutely increases tyrosine phosphorylation of the specific NMDA receptor subunit NR2B, which has recently been shown to play a role in long-term potentiation. Incubation of BDNF with cortical or hippocampal postsynaptic densities for 5 min increased tyrosine phosphorylation of the NR2B subunits in a dose-dependent manner. A maximal increase to 165% of control phosphorylation occurred at a BDNF concentration of 2 ng/ml. The BDNF action appeared to be specific, since nerve growth factor, another member of the neurotrophin gene family, had no effect on NR2B phosphorylation. Further, BDNF action was selective, since it did not alter tyrosine phosphorylation of NR2A subunits. Our results suggest that tyrosine phosphorylation of NR2B subunits of the NMDA receptor may contribute to neurotrophin modulation of postsynaptic responsiveness and long-term potentiation.

Animals↗

Functional interconnections between CA3 and the dentate gyrus revealed by current source density analysis.

The physiological interactions between the dentate gyrus (DG) and CA3 were studied in urethane-anesthetized rats by using field potential recording and current source density (CSD) analysis. Stimulation of CA3b resulted in a short-latency (<2.5-ms onset latency) antidromic population spike in both the DG and CA3c. An excitation (current sink) at the middle molecular layer (MML) was observed at 3-ms latency, possibly mediated by the backfiring of perforant path fibers that projected to both DG and CA3. CA3 stimulation also resulted in a sink at the dendritic layers of CA3c, which was likely mediated by excitatory CA3 recurrent collaterals. It was inferred that the DG was excited at the inner molecular layer (IML) after stimulation near the CA3b/CA3c border. This IML excitation (sink) probably resulted from orthodromic CA3 or hilar projections to the IML and not from mossy fiber backfiring. The IML and the CA3c dendritic sinks were blocked by an intracerebroventricular injection of a non-N-methyl-D-aspartate receptor antagonist, 6-cyano-7-nitroquinoxaline-2, 3-dione, but not by a gamma-aminobutyric acid type A (GABA(A)) receptor antagonist, bicuculline. CA3b stimulation evoked population spike bursts (3-7-ms latency) in both DG and CA3c when GABA(A) inhibition was suppressed by bicuculline, thus confirming that the excitatory afferents project from CA3b to DG and CA3c. A CA3 conditioning stimulus pulse given 30-200 ms before a perforant-path test pulse increased the amplitude of the perforant-path-evoked DG population spike (as compared with the test response without conditioning). After a moderate-intensity stimulation of CA3, a late (<20-ms latency) excitation of the MML of the DG was found. The late DG excitation was blocked by procaine injection at the medial perforant path, suggesting its origin from the medial entorhinal cortex. In conclusion, rich interactions between CA3 and other hippocampal structures were studied quantitatively by CSD analysis in vivo. We infer that CA3 provides an early excitatory feedback path to DG through recurrent collaterals or hilar interneurons and a late feedback through the medial entorhinal cortex.

Animals↗

Seasonal and spatial variability of bacterial and archaeal assemblages in the coastal waters near Anvers Island, Antarctica.

A previous report of high levels of members of the domain Archaeal in Antarctic coastal waters prompted us to investigate the ecology of Antarctic planktonic prokaryotes. rRNA hybridization techniques and denaturing gradient gel electrophoresis (DGGE) analysis of the bacterial V3 region were used to study variation in Antarctic picoplankton assemblages. In Anvers Island nearshore waters during late winter to early spring, the amounts of archaeal rRNA ranged from 17.1 to 3.6% of the total picoplankton rRNA in 1996 and from 16.0 to 1.0% of the total rRNA in 1995. Offshore in the Palmer Basin, the levels of archaeal rRNA throughout the water column were higher (average, 24% of the total rRNA) during the same period in 1996. The archaeal rRNA levels in nearshore waters followed a highly seasonal pattern and markedly decreased during the austral summer at two stations. There was a significant negative correlation between archaeal rRNA levels and phytoplankton levels (as inferred from chlorophyll a concentrations) in nearshore surface waters during the early spring of 1995 and during an 8-month period in 1996 and 1997. In situ hybridization experiments revealed that 5 to 14% of DAPI (4',6-diamidino-2-phenylindole)-stained cells were archaeal, corresponding to 0.9 x 10(4) to 2.7 x 10(4) archaeal cells per ml, in late winter 1996 samples. Analysis of bacterial ribosomal DNA fragments by DGGE revealed that the assemblage composition may reflect changes in water column stability, depth, or season. The data indicate that changes in Antarctic seasons are accompanied by significant shifts in the species composition of bacterioplankton assemblages and by large decrease in the relative proportion of archaeal rRNA in the nearshore water column.

Antarctic Regions↗

Early captopril treatment prevents hypertrophydependent gene expression in hearts of SHR.

Treatment of spontaneously hypertensive rats (SHR) with captopril (100 mg . kg-1 . day-1) throughout development and during the first 16 wk of life leads to a reduction in blood pressure and left ventricular hypertrophy. Blood pressures and hypertrophy are reduced in these animals (vs. untreated SHR) for up to 24 wk after discontinuation of the drug. We used conventional blot hybridization and Western analysis to examine hypertrophy-dependent gene expression during this period. Ventricular expression of the atrial natriuretic peptide gene was reduced by >90% at 16 wk of age in the captopril-treated SHR. Expression increased in the 24 wk after discontinuation of treatment, but remained well below that of the untreated SHR. A similar reduction in ventricular c-myc gene expression was seen with captopril treatment. Neither renal expression of the atrial natriuretic peptide gene nor ventricular expression of the c-fos gene was affected by captopril. This study demonstrates that captopril treatment during a critical period of development in the SHR leads to a sustained reduction in hypertrophy-dependent myocardial gene expression, which does not revert to levels seen in the untreated SHR after discontinuation of the drug.

Animals↗

Prolonged asymptomatic dense deposit disease in Chinese. Report of 2 cases in Taiwan.

Dense deposit disease (DDD) is a less common form of membranoproliferative glomerulonephritis (MPGN). The disease occurs predominantly in children and young adults and the prognosis is variable. DDD varies considerably in incidence among different populations and has not been reported in Chinese. Herein we reported 2 cases of DDD in young Chinese girls in Taiwan. Although 1 case (case 2) had mild hypertension, both patients had asymptomatic proteinuria and ran a benign course of 8 and 14 years, respectively. The histological features of case 1 resembled membranous glomerulonephritis (MGN) on hematoxylin-eosin stain, but revealed DDD on periodic acid Schiff and chromotrope-2R silver methenamine stains. Whereas case 2 showed focal MPGN on light microscopy, she had a fine granular immunofluorescence pattern resembling MGN. Characteristic intramembranous dense deposits were demonstrated by electron microscopy in the basement membranes of the glomeruli, Bowman's capsules and the renal tubules. Both patients were followed closely, and had stable normal renal function 1 year after renal biopsy.

Adult↗

Synergetic protective effects of combined blockade by two kinds of autolesion mediator receptor on neurological function after cervical cord injury.

OBJECTIVE: To investigate the effects of combined blockade by platelet activating factor (PAF) receptor antagonist BN52021 in combination with opiate receptor antagonist naloxone on neurological function and neurological tissue damage after cervical cord injury. METHODS: Spinal cord contusion at C6 segment was made with Allen method in cats, which were randomly divided into four groups: saline control group; BN52021 group; naloxone group; and combined treatment group with BN52021 and naloxone. Alteration of cervical cord blood flow, blood barrier permeability of the spinal cord, cervical cord tissue pathology and neurological functional scores were studied after experimental cervical cord injury. RESULTS: The animals treated with BN52021 or naloxone had significantly better functional scores than saline controls 6 weeks after injury (P < 0.05). Moreover, the combined treatment showed significantly better neurologic recovery than either naloxone or BN52021 treated animals (P < 0.05). The other indexes in combined treatment animals were also superior to those in naloxone or BN52021 treated animals. CONCLUSIONS: Combined blockade by two kinds of autolesion mediator receptor can more effectively inhibit secondary damage production and development after cervical cord injury and improve neurologic function.

Animals↗

[Protective role of endogenous nitric oxide to microcirculation of rats during burn shock].

OBJECTIVE: To investigate the role of nitric oxide (NO) in burn shock. METHODS: A model of 40% TBSA deep II burn injury in rats was used. The effects of L-NAME, the inhibitor of NO synthase, and L-Arg, the precursor of NO synthesis, on the mean arterial pressure (MAP), microcirculation of muscle, concentration of NO2(-)/NO3(-) in plasma and the survival time of animals were observed. RESULTS: The results showed that the synthesis of nitric oxide was increased significantly, accompanied with the decrease of MAP and the disturbances of microcirculation of muscle after burn. L-NAME inhibited the decrease of MAP, but aggravated the disturbances of microcirculation and shortened the survival time of animals, while L-Arg produced the contrary effects. CONCLUSION: The results indicated that the large amount of NO in blood after burn may play an early protective role to injury.

Animals↗

[A longitudinal study on growth model and velocity of term small for gestation age].

To probe into the vegetal pattern and find out the key period of promoting normal growth of term small for gestational age (TSGA), a longitudinal study on growth model and velocity of TSGA was conducted from Jan 1993 to June 1997. The body weight and length of 150 children of TSGA (57 boys, 93 girls) and 152 children as controls (58 boys, 94 girls) were measured from the 1st month to 36th month. The growth model was analysed by multilevel models. The result showed that there was a difference between the growth models of TSGA and controls. During 8 and a half months (center month), the weight, length of controls were 1.19 kg, 3.46 cm greater than those of TSGA; the weight, length of boys were 0.34 kg, 1.08 cm more than those of girls respectively. The growth velocity of TSGA was similar to that of controls. The maximal growth velocity was observed during the first 6 monthes after birth. The order of growth velocity from high to low was 1 mo. > 2 mo. > 3 mo. in length and weight, showing that children of TSGA have their own growth model. Their growth velocity should be monitored attentively. If low velocity appears one should search for the cause and adopt apropriate measures to ensure their growth in accordance with their "own track".

Body Height↗

[The effect of amlodipine, nifedipine and perindopril on insulin sensitivity and blood lipid of patients with essential hypertension].

OBJECTIVE: To investigate the effect of amlodipine, nifedipine and perindopril on insulin sensitivity(IS) and blood lipid of patients with essential hypertension(EH). METHODS: 105 EH patients were randomly divided into 3 groups: amlodipine group; nifedipine group; perindopril group. Treatment period lasted for 4 weeks. Before and after treatment, IS was measured by euglycemic insulin clamp technique with glucose metabolism rate (M) as an index of IS. RESULTS: Amlodipine, nifedipine and perindopril significantly reduced blood pressure compared with that before treatment(P < 0.01). In the EH patients with decreased IS, the M value (mg.kg-1.min-1) after the use of amlodipine, nifedipine and perindopril was higer than that before treatment (amlodipine: 6.6 +/- 1.5 Vs 4.6 +/- 0.6, P < 0.01; nifedipine: 5.2 +/- 1.2 Vs 4.4 +/- 0.6, P < 0.05; perindopril: 6.8 +/- 1.6 Vs 4.4 +/- 0.6, P < 0.01). The increase of M value(mg.kg-1.min-1), nifedipine (1.2 +/- 0.9) were significantly lower than that of amlodipine(2.1 +/- 1.1) and perindopril(2.4 +/- 1.5), P < 0.01, respectively, but no significant difference was found between amlodipine and perindopril(P > 0.05). CONCLUSION: Amlodipine and perindopril have beneficial effect on improving insulin sensitivity in EH patients with decreased insulin sensitivity. The effect of nifedipine on insulin sensitivity is lower than that of amlodipine and perindopril. Blood lipid is not significantly changed after short treatment.

Amlodipine↗