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PubMed1999

Epidemiological progresses of hemorrhagic fever with renal syndrome in China.

PURPOSE: To summarize the major achievements of Chinese work on the epidemiology and prevention of hemorrhagic fever with renal syndrome (HFRS) in recent years, and to give a general review on the present situation of HFRS in China. DATA SOURCES: Reviews and papers published in Chinese journals, relevant to the objectives, written or collected by the author; and the research work of the author. STUDY SELECTION: An outline was drafted according to the purpose given above, and the relevant materials and data were grouped together into different items outlined. DATA EXTRACTION: All the materials and data extracted were published or specially assessed. RESULTS: HFRS was first recognized in the northeastern China in 1931. It has been found prevalent also in many other parts of China since 1955, and presently, 28 out of 31 provinces (autonomous regions, or municipalities) have been proved to be its endemic areas. The total number of cases is 1,256,431 from 1950 to 1997, with 44,304 death (3.53%). 50-100 thousands of cases could be registered annually since 1981 when the presence of the Rattus-type HFRS was first identified serologically in China, with the highest peak in 1986 (115,985 cases). Three types of endemicity have been differentiated: the Apodemus-type, the Rattus-type and the mixed type of the two, by their peculiar seasonal distributions of cases and by methods of serotyping (HI, MAbs serotyping kits). The epidemiologic features of the Rattus-type HFRS are quite different from that of the Apodemus-type. 67 species of vertebrates were found to harbor hantavirus antigen or antibodies, but the chief or primary reservoir hosts are Apodemus agrarius and Rattus norvegicus only. Besides the commonly recognized enzootic mode of transmission (via contacts with the reservoir rodents or their excreta), mite transmission (including certain species of gamasid mites, and chigger mites) has been identified as the potential vectors and reservoir hosts with HFRS. Vertical transmission had been found in pregnant patients with HFRS, and in all three chief host rodents (Apodemus agrarius, Rattus norvegicus, the laboratory rats). The relatively high inapparent infection rates in the population of endemic areas of the Rattus-type HFRS after big outbreaks (8%-20%) are suggested to play a significant role in the gradual decline of the incidence of HFRS in that areas. Three kinds of inactivated vaccines against HFRS (the golden hamster kidney cell vaccine, the Mongolian gerbil kidney cell vaccine and the purified suckling mouse brain vaccine) have been successively developed and proved highly effective in the prevention of HFRS. CONCLUSION: Chinese workers on the epidemiology and prevention of HFRS in China have accomplished great achievements since 1981. As the relatively high annual incidence of HFRS sustained in recent years, control measures have to be reinforced. Many problems of HFRS and hantavirus infections are still not well understood or unclear, such as the poly-host nature, and the multi-modes of transmission, the natural history of hantaviruses and their genetic variation occurred in nature etc. The task for effective control of HFRS and the research on its epidemiology in China should be held on a high priority.

Animals↗
PubMed1999

The LifeLink Foundation and cadaver kidney transplantation in Tampa.

1. LifeLink Foundation, a not-for-profit organization, has been the driving force and absolutely essential entity for kidney and liver transplantation in Tampa providing all the components (patient, organs and clinicians) save for inpatient hospitalization. It also plays a big role in the heart transplant program. LifeLink has increased the kidney transplant rate from the first 1,000 done in 17 years to the second 1,000 in 7 years and is on a pace for the third 1,000 in 5 1/2 years. 2. Because of its innovative programs, cadaver donor procurement by the Tampa LifeLink OPO has been roughly double the national average for the past 10 years. Because of cadaver kidney availability the median wait time from activation on the wait list to transplantation over the past 5 years was 159 days. The recent transplant rate is 14.7-22.7% higher than the national average, dependent upon the parameter measured. Similar results are seen for Tampa patients awaiting heart and liver transplantation. 3. The overall outcome of 1,184 cadaver kidney transplants performed in the decade 1989-98 was similar to that reported from the UNOS database in this series of publications. a) One- and 2-year graft survival increased 2% per year over the decade with a recent one-year graft survival rate of 96%. The overall T1/2 was 10 years. b) Our disastrous 1994 results were quickly reversed by a more intense pretransplant medical evaluation, the introduction of mycophenolate mofetil, more aggressive and earlier treatment of rejection episodes, and mandatory T- and B-cell flow cytometry crossmatching for all transplants. The incidence of rejection episodes decreased from 40 to 20%, and the first year immunological graft loss decreased from 5%, to 1.9%, to 0.8%, to 1.4% and 0% over the succeeding 4 years. 4. Individual factors affecting allograft survival were strikingly similar to national data, although all did not react statistical significance probably due to the smaller numbers. a) Primary and second grafts had similar survival rates (p = 0.97) whereas the third or subsequent graft survival was 7-32% poorer (p = 0.02). b) Black recipients had survival rates 10-13% lower than Caucasians and other races (p = 0.003). c) Patients with a peak PRA > 50 had survival values 4-13% poorer than those with < 50 PRA (p = 0.14). d) Patients with 2-4 HLA mismatches had graft survival rates 4-10% poorer than those with 0-1 mismatch (p = 0.12), whereas those with 5-6 mismatches had rates 6-17% poorer (p = 0.04). e) Although 22% of our transplants were to patients > 60 years of age, there was no difference (p = 0.81 to 0.90) in graft survival for the age groups 0-40, 41-60 and > 61. However, the proportion of grafts lost due to patient death compared with all allografts lost, was very different at 21% in the youngest group, 43% in those 41-60 years of age, and 63% in recipients > 61 years. 5. The rate of delayed graft function with imported kidneys was higher (27 vs. 16%, p = 0.006) but essentially the same as local kidneys with the same ischemia times. However, 41% of local kidneys were transplanted within 12 hours of procurement. Totally, 78% of local kidneys were transplanted within 18 hours (11% DGF rate) versus 79% of imports being transplanted at > 18 hours (32% DGF rate). Ischemia time, not the kidney source is the key issue since: a) There was no difference in overall graft survival of imported versus local kidneys (p = 0.95) nor in comparing local versus import kidneys with (p = 0.66) or without (p = 0.69) DGF. b) There was, however, a 11-17% overall poorer graft survival over 3 years in kidneys with DGF (p < 0.001) seen with both local (9-18% poorer, p = 0.0002) and imported (12-19% poorer, p = 0.008) kidneys. c) Kidneys displaying DGF came from older donors (40 vs. 34 years, p = 0.023) and had longer ischemia times (21 vs. 15 hours, p < 0.0005). 6. Dual kidney transplants were started in late 1996 with older or marginal donors to provide a better chance of success fo

Adolescent↗
PubMed1996

Towards validation of the Big Blue transgenic mouse mutagenesis assay: the mutational spectrum of ex vivo pinpoint mutant plaques.

To explore further the origin of spontaneous mutations recovered with the Big Blue transgenic mouse mutagenesis assay, the spectrum of ex vivo mutations from pinpoint mutant plaques was determined and compared with the spectrum of putatively mouse-derived mutations from circular, mutant plaques. The entire lacI gene and lacZ operator region from 62 pinpoint blue plaques was sequenced. The observed mutational spectrum of pinpoint mutants differed significantly from that seen in circular mutants (p < 0.0001). Only four percent of the mutations were transitions at CpG sites whereas this type of mutation was the most common (35%) in circular mutants. Microdeletions/microinsertions were seen more frequently in pinpoint mutants relative to circular mutants. Four base pair deletion/insertion events at the E. coli hotspot tandem repeats were seen in 10 of 62 (16%) pinpoint mutants and minor hotspots of mutation were observed at bp 141 and 1110. The mutational spectrum of pinpoint mutants provides further evidence that most circular mutants originate in mouse.

Age Factors↗
PubMed2005

Percutaneous radiofrequency ablation of renal cell carcinoma.

BACKGROUND: Preliminary data regarding the use of percutaneous radiofrequency ablation (RFA) for the treatment of renal cell carcinoma (RCC) are encouraging, and show the technique to be associated with minimal morbidity. Thus, the current study was designed to evaluate the clinical applications, treatment efficacy, and complications of percutaneous RFA in RCC. METHODS: From February 2003 to February 2004, 12 consecutive patients with histopathologically proven RCC underwent imaging-guided percutaneous RFA. The mean age of the patients (8 men and 4 women) was 76 years (range, 56-87 years), and mean tumor diameter was 3.7 cm (range, 2.2-8.0 cm). The efficacy of RFA was evaluated with contrast-enhanced, dynamic computed tomography (CT) performed 1 month after treatment, and then every 3 months. A Radionics device with an internally cooled electrode was used in 7 patients, and a radiofrequency interstitial tissue ablation (RITA) device with an expandable needle electrode was used in 5. Complete necrosis was defined as a lack of contrast enhancement in the treated region on follow-up CT studies. RESULTS: Overall, 16 sessions of RFA were performed for 12 solitary renal tumors in 12 patients: 8 patients underwent a single RFA session, whereas 4 had 2 sessions. Dynamic CT after RFA showed complete necrosis in 9 of 12 tumors. In 3 patients with tumors of 4.5-8.0 cm in diameter, enhancement of residual tissue was observed after RFA treatment, thus indicating residual tumor. Complete tumor necrosis was seen in all 5 tumors (100%) of diameter < or = 3.0 cm; 3 of 4 tumors (75%) of diameter 3.1-5.0 cm; and 1 of 3 tumors (33%) of diameter > 5.0 cm. A big subcapsular hematoma, which was found in 1 patient after RFA, resolved completely within 10 months without treatment; no serious complications occurred in the other 11 patients. CONCLUSION: Percutaneous RFA is effective in the treatment of RCC. It is most successful for tumors not larger than 3 cm in diameter, and has a satisfactory success rate in tumors of 3-5 cm in diameter. The rate of serious complications of RFA is low. Further studies are necessary to determine the long-term efficacy of RFA in RCC.

Aged↗
PubMed1999

Effects of a specific endothelin-converting enzyme inhibitor on cardiac, renal, and neurohumoral functions in congestive heart failure: comparison of effects with those of endothelin A receptor antagonism.

BACKGROUND--Endothelin (ET)-1 is generated from big ET-1 by endothelin-converting enzyme (ECE). Plasma big ET-1 and ET-1 levels are strongly related to survival in patents with congestive heart failure (CHF). Because selective enzymatic processing of ET-1 formation appears to be an important therapeutic target for CHF, we investigated the acute effects of a specific ECE inhibitor on cardiorenal and endocrine functions in CHF compared with those of a selective ETA receptor antagonist. METHODS AND RESULTS--CHF was induced in beagle dogs by rapid right ventricular pacing (270 bpm, 14 days). Two incremental doses of a specific ECE inhibitor, FR901533, or a selective ETA receptor antagonist, FR139317 (1 and 3 mg/kg, n=8, respectively), were injected into dogs with CHF. FR901533 and FR139317 decreased mean arterial pressure and pulmonary capillary wedge pressure associated with reduction in systemic and pulmonary vascular resistance. These agents increased cardiac output but did not affect left ventricular fractional shortening. FR139317 exerted a greater depressor effect on mean arterial pressure than FR901533 (P<0.05). These agents decreased plasma atrial natriuretic peptide levels, but only FR901533 decreased plasma renin activity, angiotensin II, and aldosterone levels. Neither agent changed the plasma norepinephrine level despite the fall in blood pressure. These drugs increased the urinary water and sodium excretion rate associated with increases in the glomerular filtration rate and renal plasma flow, and the incremental magnitude induced by FR139317 was larger than that by FR901533 (P<0.05). CONCLUSIONS--An ETA receptor antagonist appeared to induce greater vasodilative effects on systemic and renal vasculature in CHF than an ECE inhibitor. However, the ECE inhibitor reduced the secretion of neurohumoral factors that are activated in proportion to the severity of CHF. Our acute complementary data may support the importance of the role of ECE in CHF and provide a rationale foundation for investigating the usefulness of long-term treatment with ECE inhibitors in CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Regimens of less than six months for treating tuberculosis.

BACKGROUND: WHO recommends 6 months of treatment in TB programmes. OBJECTIVES: The purpose of this review is to assess the effects of regimens lasting less than 6 months compared with longer regimens in the treatment of active TB. SEARCH STRATEGY: Search strategy: MEDLINE 1955-, Cochrane Infectious Diseases Trials Register, existing reviews, and researchers in the field. Date of the most recent search: January 1999. SELECTION CRITERIA: Randomized trials comparing two or more TB drug regimens, in which at least one regimen was <6 months and it was compared with at least one regimen that lasted longer, in any patients with active TB. DATA COLLECTION AND ANALYSIS: One reviewer extracted data and assessed trial quality. MAIN RESULTS: Seven trials with a total of 9 comparisons of <6 months (range: 2-5 months) versus longer treatment were included. About 2200 patients were in the shorter regimens and about 1900 in the longer regimens (the same comparison groups were used for more than one shorter regimen, in two studies). Relapse rates were consistently higher after shorter duration treatment regimens, regardless of the comparison made, though they were all relatively low. Results were significantly better in the longer groups in the meta-analyses of 2, 3, and 4 months of treatment vs longer treatment (Peto OR = 6.1 [95%CI 2.19,17.01], 3.67 [2.42,5.58], 3.64 [1.71,7. 75] but not in the single trial of 5 vs. 7 months (Peto OR = 2.24 [0. 90,5.59]. Relapse rates after longer (comparison) regimens ranged from 0-7% at one year (or more), and in the shorter treatment arms, they ranged from 1-9% in 8 trials, and18% relapsed in the one remaining. There was little or no difference in the rates of adverse reactions or toxicity requiring a change of regimen or discontinuation of treatment. The "sterilizing efficacy" at the end of treatment varied little among treatments, providing no predictive value for relapse rates. Few or no deaths were reported in the individual trials, and in no case did enough deaths occur for a comparison of short vs. long regimens. REVIEWER'S CONCLUSIONS: Longer periods of treatment (at least up to 6 months) result in higher success rates in patients with active TB, but the differences are small. Under field conditions, where adherence to treatment is a big problem, and shorter regimens might improve adherence, these differences may not be evident. A comparison of <6 months vs. 6 months of treatment under programme conditions would be needed to determine this.

Antitubercular Agents↗
PubMed2006

Free-ranging European bisons accumulate more cadmium in the liver and kidneys than domestic cattle in north-eastern Poland.

It has been shown that free-ranging big game animals accumulate several-fold more cadmium (Cd) in the liver and kidneys than domestic animals. To examine possible reasons for this difference, in the present work we determined the concentrations of Cd in the liver and kidney cortex of European bisons (n=23) from Białowieza Forest (north-eastern Poland) and domestic cattle (n=15) from the same region; in addition, analyses of Cd in the grasses and soil as well as of soil pH were carried out. The accumulation of Cd in liver and kidney cortex of the female bisons correlated significantly with the age up to 7 years, but stabilized thereafter. The 7-12-year-old bisons had 2.14- and 2.25-fold higher concentrations of Cd in the liver and kidney cortex, respectively, than the age-matched domestic cattle. Notably, the Cd levels in the liver and kidneys of the 8-12-year-old cattle were comparable to those found in the 2-year-old and 4-6-year-old bisons, respectively. The content of Cd in the grasses from Białowieza Forest appeared to be 2.1-fold higher than that in the plants from the pastures. Similarly, the concentration of water-extractable Cd in the soil was 2.7-fold greater in Białowieza Forest than in the pastures, despite the fact that nitric acid-extractable Cd (total Cd) was similar in the soils from the two sites. The concentration of water-extractable Cd in the soil as well as the content of Cd in the grasses inversely correlated with soil pH, which appeared to be significantly lower in Białowieza Forest. These data indicate that soil pH is probably responsible for the higher concentrations of Cd in the feed and tissues of bisons as compared with those of domestic cattle.

Animals↗
PubMedDate not supplied

[Statistical and frequency-amplitude characteristics of ultra-weak emissions of loach eggs and embryos under normal conditions and on their optic interactions. II. Changes in characteristics of ultra-weak emissions upon optic interaction of groups of embryos of different ages. ].

We compared the characteristics of ultraweak emissions from groups of loach embryos of different ages in the presence or absence of optic interaction. The percentage of zero values of emission gradually increased during the first hour of optic interaction. The number and height of rare big pulses estimated by the value of kurtosis increased in parallel. In addition, the correlation between the Fourier spectra of optically interacting samples decreased at a higher rate than in the absence of optical contact. Just after the 1-hour optic interaction was terminated, the number of high pulses decreased in a younger interacting group and increased in the older one and the farther away the partner groups were in developmental stages, the more pronounced these differences were. Measurements of the Fourier spectra after long-term (12-22-hour) optic interactions have shown that an "exchange" of autocorrelation characteristics of the spectra took place among the samples: the sums of autocorrelation coefficients were inverted in the vast majority of cases, often with an "overshoot" or, at least, were smoothed over with reference to the control samples. We conclude that the previously described effects of optic interactions between groups of loach embryos of different ages could be due to changes in the frequency spectra of their ultraweak emissions.

Animals↗
PubMed1999

Constitutive lysosomal targeting and degradation of bovine endothelin-converting enzyme-1a mediated by novel signals in its alternatively spliced cytoplasmic tail.

Endothelin-converting enzyme-1 (ECE-1) is a type II membrane protein that catalyzes the proteolytic activation of big endothelin-1 to endothelin-1 (ET-1). The subcellular distribution of ECE-1, and hence the exact site of physiological activation of big ET-1, remains controversial. Here, we demonstrate with several complementary methods that the two alternatively spliced bovine ECE-1 isoforms, ECE-1a and ECE-1b, differing only in the first 30 amino acids of their N-terminal cytoplasmic tails, exhibit strikingly distinct intracellular sorting patterns. Bovine ECE-1a, which is responsible for the intracellular cleavage of big ET-1 in endothelial cells, is constitutively recruited into the lysosome, where it is rapidly degraded. In contrast, bovine ECE-1b, the isoform found in cultured smooth muscle cells, is transported to the plasma membrane by a default pathway and functions as an ectoenzyme. Mutational analyses reveal that the N-terminal tip of the cytoplasmic domain of bovine ECE-1a contains novel proline-containing signals that mediate constitutive lysosomal targeting. Analyses of chimeric ECE-1/transferrin receptors demonstrate that the cytoplasmic tail of bovine ECE-1a is sufficient for the lysosomal delivery and rapid degradation. Our results suggest that the distinct intracellular targeting of bovine ECE-1 isoforms may provide new insights into functional aspect of the endothelin system and that the cell permeability of ECE inhibitor compounds should be carefully considered during their pharmacological development.

Alternative Splicing↗
PubMed2003

Enzymes encoded by the farnesyl diphosphate synthase gene family in the Big Sagebrush Artemisia tridentata ssp. spiciformis.

Farnesyl diphosphate synthase catalyzes the sequential head-to-tail condensation of two molecules of isopentenyl diphosphate with dimethylallyl diphosphate. In plants the presence of farnesyl diphosphate synthase isozymes offers the possibility of differential regulation. Three full-length cDNAs encoding putative isoprenoid synthases, FDS-1, FDS-2, and FDS-5, with greater than 89% similarity were isolated from a Big Sagebrush Artemisia tridentata cDNA library using a three-step polymerase chain reaction protocol. One of the open reading frames, FDS-5, encoded a protein with an N-terminal amino acid extension that was identified as a plastidial targeting peptide. Recombinant histidine-tagged versions of three proteins were purified, and their enzymatic properties were characterized. FDS-1 and FDS-2 synthesized farnesyl diphosphate as the final chain elongation product, but their kinetic behavior varied. FDS-1 prefers geranyl diphosphate over dimethylallyl diphosphate as an allylic substrate and is active at acidic pH values compared with FDS-2. In contrast, FDS-5 synthesized two irregular monoterpenoids, chrysanthemyl diphosphate and lavandulyl diphosphate, when incubated with dimethylallyl diphosphate and an additional product, the regular monoterpene geranyl diphosphate, when incubated with isopentenyl diphosphate and dimethylallyl diphosphate. Specific cellular functions are proposed for each of the three enzymes, and a scenario for evolution of isoprenyl synthases in plants is presented.

Alkyl and Aryl Transferases↗
PubMed2002

Nucleotide sequence and genomic organization of an ophiovirus associated with lettuce big-vein disease.

The complete nucleotide sequence of an ophiovirus associated with lettuce big-vein disease has been elucidated. The genome consisted of four RNA molecules of approximately 7.8, 1.7, 1.5 and 1.4 kb. Virus particles were shown to contain nearly equimolar amounts of RNA molecules of both polarities. The 5'- and 3'-terminal ends of the RNA molecules are largely, but not perfectly, complementary to each other. The virus genome contains seven open reading frames. Database searches with the putative viral products revealed homologies with the RNA-dependent RNA polymerases of rhabdoviruses and Ranunculus white mottle virus, and the capsid protein of Citrus psorosis virus. The gene encoding the viral polymerase appears to be located on the RNA segment 1, while the nucleocapsid protein is encoded by the RNA3. No significant sequence similarities were observed with other viral proteins. In spite of the morphological resemblance with species in the genus Tenuivirus, the ophioviruses appear not to be evolutionary closely related to this genus nor any other viral genus.

Base Sequence↗
PubMed1999

Horseshoe crab acetyl group-recognizing lectins involved in innate immunity are structurally related to fibrinogen.

We have characterized and cloned newly isolated lectins from hemolymph plasma of the horseshoe crab Tachypleus tridentatus, which we named tachylectins 5A and 5B (TLs-5). TLs-5 agglutinated all types of human erythrocytes and Gram-positive and Gram-negative bacteria. TLs-5 specifically recognize acetyl group-containing substances including noncarbohydrates; the acetyl group is required and is sufficient for recognition. TLs-5 enhanced the antimicrobial activity of a horseshoe crab-derived big defensin. cDNA sequences of TLs-5 indicated that they consist of a short N-terminal Cys-containing segment and a C-terminal fibrinogen-like domain with the highest sequence identity (51%) to that of mammalian ficolins. TLs-5, however, lack the collagenous domain found in a kind of "bouquet arrangement" of ficolins and collectins. Electron microscopy revealed that TLs-5 form two- to four-bladed propeller structures. The horseshoe crab is equipped with a unique functional homologue of vertebrate fibrinogen, coagulogen, as the target protein of the clotting cascade. Our observations clearly show that the horseshoe crab has fibrinogen-related molecules in hemolymph plasma and that they function as nonself-recognizing lectins. An ancestor of fibrinogen may have functioned as a nonself-recognizing protein.

ABO Blood-Group System↗
PubMed2003

Urban garbage disposal and management in China.

This paper, probing into the present situation of urban domestic garbage by analyzing its growing trend, compositional change and regional difference, reveals the problems existing in its disposal and management in China. Meanwhile, a questionnaire was conducted in five big cities around China for surveying urban residents' attitudes towards garbage disposal and management policies and measures. Results showed the output of urban domestic garbage in Chinese cities is ever increasing, and the recoverable materials and energy in garbage composition are also increasing. The population growth, economic development, and increase of residents' expenditure level are the main factors influencing the growing output and changing composition of the garbage. Information acquired from the questionnaire showed that majority of the urban residents are in favor of the garbage reduction policies and managerial measures and are willing to collaborate with municipal government in battling against garbage. Based on the analysis and questionnaire, some policymaking-oriented suggestions such as operating the garbage disposal from a social welfare service to a sector of profit-gaining enterprises, transferring the garbage management from passive end control to active source control, promoting the classified garbage collection in cities around China, and charging garbage fees for its cleanup and disposal, have also been put forward in the paper.

China↗
PubMed2002

[Trends in antibiotic consumption in Spain, 1985-2000].

BACKGROUND: The purpose of this study was to analyse the trend in antibiotics consumption to draw on the National Health System (NHS) over the last 16 years in Spain and its different Autonomous Communities (AC). MATERIAL AND METHOD: Consumption data for all antibiotics used in Spain, either alone or in fixed-dose combinations, were obtained using the database ECOM. This database includes all the packages sold through retail pharmacies and reimbursed by the NHS. Data are expressed as defined dairy doses per 1,000 inhabitants per day (DHD), in accordance with the methodology recommended by the World Health Organization. Demographic data were provided by the National Institute of Statistics. RESULTS: In 1985 the overall consumption of antibiotics was 21.9 DHD, while in 2000 it was 20.4 DHD. It was possible to distinguish three phases over the study period. The first phase lasts until 1989, where a mild decreasing trend was observed (1.1 DHD; 5.0%), mainly due to the fall of fixed-dose combinations of antibiotics and the association of sulfamethoxazole-trimethoprim. The second phase, lasting until 1996, was characterized by a generalized increase in the consumption in all AC, with an average of 2.3 DHD (+ 11.1%), ranging from 0.4 to 4.6 DHD; this increase was mainly due to the marketing of new macrolides, cephalosporins and quinolones. Finally, there was a third phase beginning in 1996, where the consumption of antibiotics came into a sustained and generalized decline, ranging from 0.5 to 5.1 DHD, and depending on the AC (national average 2.7 DHD, 11.7% lower than that in 1996). This latter trend was mainly due to the fall of wide-spectrum penicillins. Differences between AC regarding the level of consumption were huge over the study period, although the pattern of use was quite similar. There was, for instance, a difference of 10.4 DHD between Región de Murcia and Islas Baleares in 2000, or 9.9 DHD between the former and Madrid in the same year. CONCLUSIONS: The consumption of antibiotics in Spain and all its AC has declined since 1996, probably related to the campaigns launched by public administrations to promote the rational use of these agents. The main subgroup involved in this trend is wide-spectrum penicillins. Differences in antibiotics use between AC are too big to be accounted for by different epidemic patterns and, therefore, should be analysed further.

Anti-Bacterial Agents↗
PubMed2006

Characterization of big bang, a novel gene encoding for PDZ domain-containing proteins that are dynamically expressed throughout Drosophila development.

PDZ (PSD-95, Discs-large, ZO-1) domain proteins often function as scaffolding proteins and have been shown to play important roles in diverse cellular processes such as the establishment and maintenance of cell polarity, and signal transduction. Here, we report the identification and cloning of a novel Drosophila melanogaster gene that is predicted to produce several different PDZ domain-containing proteins through alternative promoter usage and alternative splicing. This gene, that we have named big bang (bbg), was first identified as C96-GAL4, a GAL4 enhancer trap line that was generated in our lab. To further characterize bbg, its expression pattern was examined in ovaries, embryos, and late third instar larvae using UAS reporter gene constructs, in situ hybridization, or immunocytochemistry. In addition, the expression of alternatively spliced transcripts was examined in more detail using in situ hybridization. We find that during embryogenesis bbg is predominantly expressed in the developing gut, but it is also expressed in external sensory organs found in the epidermis. In the late third instar larva, bbg is expressed along the presumptive wing margin in the wing disc, broadly in the eye disc, and in other imaginal discs as well as in the brain. The expression patterns observed are dynamic and specific during development, suggesting that like other genes that encode for several different PDZ domain protein isoforms, bbg likely plays important roles in multiple developmental processes.

Alternative Splicing↗
PubMed1998

Molecular biological characterization of enterovirus variant isolated from patients with aseptic meningitis.

In Korea, there was a big outbreak of aseptic meningitis in 1993. Six clinical isolates of enterovirus were obtained from patients with aseptic meningitis and were identified as echovirus type 9 by serotyping with a pool of neutralizing antisera. For molecular characterization of the isolates, the nucleotide sequences of 5'-noncoding region (NCR), VP4, VP2, VP1, 2A and 2C regions of the isolates were compared with the corresponding regions of echovirus type 9 Hill and Barty strains. Unlike Hill strain, Barty strain contained a C-terminal extension to the capsid protein VP1 with an RGD (argnine-glycine-aspartic acid) motif. To determine whether similar structural features were present in our isolates, their nucleotide sequences including the VP1 region were analyzed. All isolates exhibited the VP1 extension with the RGD motif. We concluded the Korean isolates in the year of 1993 as the echovirus type 9 Barty strain although the isolates showed 15-20% nucleotide sequence differences in the several genomic regions.

5' Untranslated Regions↗
PubMed1992

Monoclonal antibodies to human endothelin-1: characterization and utilization in radioimmunoassay and immunocytochemistry.

A host of monoclonal antibodies directed against human endothelin-1 (ET-1) has been developed and characterized. The antibodies reacted with ET-1 specifically and with high affinity, as determined by competition analysis and sucrose density gradients. The antibodies did not cross-react with neuropeptide YY, beta-endorphin, calcitonin gene-related peptide, secretin or somatostatin. The antibodies cross-reacted with big endothelin (B-ET), endothelin-2 (ET-2), vasointestinal constrictor peptide (VIC), and endothelin-3 (ET-3) albeit with varying affinity but did not cross-react with sarafotoxin (SRTX-6b). None of the antibodies reacted with the C-terminal hexapeptide (HXPT) of ET-1, indicating that the epitopes are not located within this region of ET-1. The monoclonal antibodies exhibited binding activity in dilutions ranging from 1:1000, to 1:10(6). The isotypes of the monoclonal antibodies were determined by competition binding assay. Six of the monoclonal antibodies were of the IgG gamma 1, two were IgM and one of the IgG gamma 2a subclass. The antibodies detected immunoreactive ETs by radioimmunoassay and in immunocytochemical localization, suggesting the potential use of these antibodies as tools to determine the concentration of ETs in biological fluids and in immunocytochemical localization of ETs in specific cell types in various tissues.

Amino Acid Sequence↗
PubMed2002

The nucleotide sequence of RNA1 of Lettuce big-vein virus, genus Varicosavirus, reveals its relation to nonsegmented negative-strand RNA viruses.

The complete nucleotide sequence of RNA1 from Lettuce big-vein virus (LBVV), the type member of the genus Varicosavirus, was determined. LBVV RNA1 consists of 6797 nucleotides and contains one large ORF that encodes a large (L) protein of 2040 amino acids with a predicted M(r) of 232,092. Northern blot hybridization analysis indicated that the LBVV RNA1 is a negative-sense RNA. Database searches showed that the amino acid sequence of L protein is homologous to those of L polymerases of nonsegmented negative-strand RNA viruses. A cluster dendrogram derived from alignments of the LBVV L protein and the L polymerases indicated that the L protein is most closely related to the L polymerases of plant rhabdoviruses. Transcription termination/polyadenylation signal-like poly(U) tracts that resemble those in rhabdovirus and paramyxovirus RNAs were present upstream and downstream of the coding region. Although LBVV is related to rhabdoviruses, a key distinguishing feature is that the genome of LBVV is segmented. The results reemphasize the need to reconsider the taxonomic position of varicosaviruses.

3' Untranslated Regions↗