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PubMed2001

BIG: a calossin-like protein required for polar auxin transport in Arabidopsis.

Polar auxin transport is crucial for the regulation of auxin action and required for some light-regulated responses during plant development. We have found that two mutants of Arabidopsis-doc1, which displays altered expression of light-regulated genes, and tir3, known for its reduced auxin transport-have similar defects and define mutations in a single gene that we have renamed BIG. BIG is very similar to the Drosophila gene Calossin/Pushover, a member of a gene family also present in Caenorhabditis elegans and human genomes. The protein encoded by BIG is extraordinary in size, 560 kD, and contains several putative Zn-finger domains. Expression-profiling experiments indicate that altered expression of multiple light-regulated genes in doc1 mutants can be suppressed by elevated levels of auxin caused by overexpression of an auxin biosynthetic gene, suggesting that normal auxin distribution is required to maintain low-level expression of these genes in the dark. Double mutants of tir3 with the auxin mutants pin1, pid, and axr1 display severe defects in auxin-dependent growth of the inflorescence. Chemical inhibitors of auxin transport change the intracellular localization of the auxin efflux carrier PIN1 in doc1/tir3 mutants, supporting the idea that BIG is required for normal auxin efflux.

Amino Acid Sequence↗
PubMed1985

Involvement rate in two-car crashes versus driver age and car mass of each involved car.

This work was performed to investigate how the likelihood of a two-car crash depends on the driver age and car mass for each of the two involved cars, and also to examine the special case of cars of similar mass crashing into each other. Data on 108 044 cars involved in police reported two-car crashes occurring in New York State in 1971 and 1972 were fitted to a function of the driver age and car mass for each of the two involved cars. Car registrations are used to estimate exposure. The special case of crashes between cars of similar mass is considered because of prior results on driver injuries in such crashes. It is found that "small-small" crashes (defined as a 900 kg car crashing into another 900 kg car) are about 0.3 times as likely as "big-big" crashes (an 1800 kg car crashing into another 1800 kg car), assuming equal numbers of cars driven by drivers of the same age. Combining the present results with earlier findings of increased injury risk in small-small crashes gives that such crashes injure about 70% as many drivers as big-big crashes when normalized for numbers of cars and driver age. That is, it is concluded that small-small crashes produce 30% fewer injuries than do big-big crashes.

Accidents, Traffic↗
PubMed2006

Reasons for condom use among young people in KwaZulu-Natal: prevention of HIV, pregnancy or both?

CONTEXT: High levels of HIV/AIDS and unwanted pregnancy among young people are urgent public health problems in South Africa. Studies among youth have generally focused on protection against one or the other of these risks, but not both. METHODS: Data collected in 2001 from 2,067 sexually active men and women aged 15-24 in KwaZulu-Natal were examined in bivariate and multivariate analyses to assess reasons for condom use, and levels and determinants of use. RESULTS: Overall, 59% of respondents said that they used condoms at last sexual intercourse, including 6% who used them with another method. The main reason for use (cited by 64% of users) was protection against both pregnancy and HIV infection. Two-thirds of respondents thought that becoming or making someone pregnant in the next few weeks would be a big problem; fewer than one in five viewed their risk of HIV infection as medium or high. Among both sexes, young people who would consider a pregnancy highly problematic were more likely to use condoms than their counterparts who would view a pregnancy as no problem (odds ratios, 1.4-2.3). In sharp contrast, young men and women who perceived themselves as having a medium to high risk of HIV infection were less likely to use condoms than their counterparts who perceived themselves as being at no risk (0.2-0.3). CONCLUSION: Prevention programs could increase condom use in this population by increasing awareness of the twin risks of pregnancy and HIV infection, and by promoting condoms for protection against these dual risks.

Adolescent↗
PubMed2004

Personality characteristics and trait clusters in final stage astronaut selection.

INTRODUCTION: This paper presents personality testing data from final stage applicants to the NASA astronaut program. Questions addressed include whether personality predicted final selection into the astronaut corps, whether women and men demonstrated typical gender differences in personality, and whether three characteristic clusters found in other high performance populations replicated in this group. METHODS: Between 1989 and 1995, 259 final stage astronauts completed the Personal Characteristic Inventory (PCI) which assesses personality characteristics related to the broad traits of Instrumentality and Expressivity. In addition, 147 of these individuals also completed an abbreviated version of the NEO Five Factor Inventory (NEO-FFI) which assesses the "Big Five" traits of Neuroticism, Extraversion, Openness, Agreeableness, And Conscientiousness. RESULTS: Three previously identified trait clusters (Right, Wrong, and No Stuff) were found to replicate in this population. No differences were found on the PCI or on the modified NEO-FFI between applicants who were chosen to become astronauts (n = 63) and those who were not (n = 196). Men scored higher than women on competitiveness, but lower on expressivity and achievement strivings. DISCUSSION: These analyses suggest that the "Right Stuff," "Wrong Stuff" and "No Stuff" clusters originally described in airline pilots and other high performance groups also exist within this population. Consistent with findings from other high performance populations, men and women tend to differ to a lesser extent than found in the general population, particularly on traits related to achievement motivation. Personality trait testing did not predict which applicants were most likely to be accepted into the astronaut corps.

Astronauts↗
PubMed2004

Postoperative analgesia in infants and children: new developments.

Nowadays, postoperative pain control in infants and children is a big challenge. The only effective solution is a multidisciplinary work with accurate guidelines, starting from the preoperative period throughout the surgery and arriving at the postoperative period. The approach must be scientific, based on the recent studies and research. In recent years, there has been a renaissance in regional anesthesia in children, in part because of a greater concern about postoperative pain management in young patients, and in part because of technical advances in equipment to perform the blocks. In fact several techniques and routes can be used for pain treatment but all have side effects. We await data from the use of COX2 inhibitors, surely the future of NSAIDs, with valid anti-inflammatory action and fewer side effects in children. When possible/not controindicated, regional analgesia is often the best choice. Recently continuous peripheral infusion is successfully applied in infants and children, due to its safety, efficacy and well limited localisation of analgesia. All the variety of peripheral nerve blocks used in adults can be used in pediatrics. The indications to place a catheter for a continouos peripheral nerve blocks are the followings: major orthopedic procedures; the procedure is scheduled to last more than two hours; congenital malformation of foot or hand; fracture reduction; traction of femur fracture; when postoperative pain therapy is necessary for several days; painful physical therapy. The commonly performed continuous peripheral blocks in children are the brachial plexus block (parascalene or axillary), the femoral nerve block, the fascia iliaca block, the sciatic nerve block with the lateral or with the popliteal approach. In these last two years also our group performed several continuous peripheral nerve blocks particularly axillary, femoral and sciatic for major orthopedic surgery and trauma. In our institution, we use a bolus dose of 0.5-1 ml/kg (depending on the nerve to be blocked) of ropivacaine 0.2% or levobupivacaine 0.25% with clonidine 2 microg/kg and then in infants older than 6 months and children we use a continuous infusion of 0.1-0.3 ml/kg/h of 0.2% ropivacaine or 0.25% levobupivacaine with clonidine 3 microg/kg/24h for 48-72 hours. For older children doses and concentrations are usually the same used in adults.

Analgesia↗
PubMed1993

Trends in medical management of acute myocardial infarction, Auckland 1983-90.

AIMS: To examine changes in the medical management of acute myocardial infarction in the Auckland region between 1983 and 1990. METHODS: 6190 patients aged 25-64 years with myocardial infarction were identified utilising a population based register, the ARCOS study. Data were collected on resuscitation attempts, transportation to hospital, coronary care unit (CCU) stay and medication use before and during the CCU stay. RESULTS: The median time delay between onset of symptoms and arrival at the CCU decreased by approximately 7 minutes per year. The average length of CCU stay decreased from 2.9 to 2.7 days and there were between hospital variations in length of CCU stay. The most striking change in drug therapy before the event was the increase in the use of antiplatelet agents from 5% in 1983 to 18.3% in 1990. There was also a big increase in the proportion of patients using antiplatelets (3.5 fold) and thrombolytic drugs (5.5 fold) during the CCU stay, in 1990, 50% of patients received thrombolytic agents and 56% received antiplatelet agents. CONCLUSION: The use of drugs of proven benefit could be further increased although it appears that major improvements in mortality rates will come primarily from primary prevention.

Adult↗
PubMed1993

Effects of phosphoramidon in endothelial cell cultures on the endogenous synthesis of endothelin-1 and on conversion of exogenous big endothelin-1 to endothelin-1.

Several studies have shown that phosphoramidon (PHOS) reduces the release of endothelin-1 (ET-1) from cultured endothelial cells. Moreover, the main endothelin-converting enzyme (ECE) activity in these cells is a membrane-bound metallopeptidase that is also inhibited by PHOS. We have investigated further the role of the PHOS-sensitive ECE in the conversion of big ET-1 to ET-1. ET-1 was measured using a radioimmunoassay specific for the C-terminal ET[16-21] sequence. The effect of PHOS on the production of ET-1 from endogenous precursors was determined using cultured bovine aortic endothelial cells (BAECs) and the human endothelial cell line (EA.hy 926). The concentrations of ET-1 accumulating in the medium over 24 h from BAECs were lowered by PHOS (-27% 10 microM, -76% 100 microM). In contrast, with EA.hy 926 cells, the same concentrations of PHOS increased by five- to sixfold the amount of ET-1 present in the medium after 24-h incubation. In other experiments, incubation of big ET-1 (1 microM) with intact BAECs or EA.hy 926 cells resulted in the generation of ET-1, and with both cell types this was inhibited by PHOS (IC50: BAECs = 6.4 microM; EA.hy 926 = 0.26 microM). These results are consistent with both cell types having a PHOS-sensitive ECE that is readily accessible to exogenous big ET-1 and is therefore probably located on the plasma membrane. Furthermore, another intracellular ECE may play a part in the endogenous intracellular formation of ET-1 in EA.hy 926 cells.

Amino Acid Sequence↗
PubMed1998

Effects of chromosome underreplication on cell division in Escherichia coli.

The key processes of the bacterial cell cycle are controlled and coordinated to match cellular mass growth. We have studied the coordination between replication and cell division by using a temperature-controlled Escherichia coli intR1 strain. In this strain, the initiation time for chromosome replication can be displaced to later (underreplication) or earlier (overreplication) times in the cell cycle. We used underreplication conditions to study the response of cell division to a delayed initiation of replication. The bacteria were grown exponentially at 39 degreesC (normal DNA/mass ratio) and shifted to 38 and 37 degreesC. In the last two cases, new, stable, lower DNA/mass ratios were obtained. The rate of replication elongation was not affected under these conditions. At increasing degrees of underreplication, increasing proportions of the cells became elongated. Cell division took place in the middle in cells of normal size, whereas the longer cells divided at twice that size to produce one daughter cell of normal size and one three times as big. The elongated cells often produced one daughter cell lacking a chromosome; this was always the smallest daughter cells, and it was the size of a normal newborn cell. These results favor a model in which cell division takes place at only distinct cell sizes. Furthermore, the elongated cells had a lower probability of dividing than the cells of normal size, and they often contained more than two nucleoids. This suggests that for cell division to occur, not only must replication and nucleoid partitioning be completed, but also the DNA/mass ratio must be above a certain threshold value. Our data support the ideas that cell division has its own control system and that there is a checkpoint at which cell division may be abolished if previous key cell cycle processes have not run to completion.

Cell Cycle↗
PubMed2001

Localization of the endothelin system in aldosterone-producing adenomas.

Endothelin-1 (ET-1) could play a role in the regulation of aldosterone secretion of the human adrenal gland. The presence of the endothelin-converting enzyme 1 (ECE-1) and ET-1 suggests that there is a local ET system in the adrenal cortex, but the in situ synthesis of ET-1 remains to be confirmed. The cellular distribution of the whole ET system was evaluated in 20 cases of aldosterone-producing adenomas. Polymerase chain reaction studies gave strong signals for ECE-1 mRNA and the mRNAs for endothelin type A (ET(A)) and B (ET(B)) receptors and faint signals for prepro-ET-1 mRNA. In situ hybridization showed ET(A) receptors scattered throughout the adenoma, in both secretory cells and vascular structures (score, +). There were more ET(B) receptors (score, ++), but they were restricted mainly to the endothelium. ECE-1 mRNA and protein were ubiquitous and abundant in secretory cells (score, +++) and vascular structures (score, ++); the enzyme was active on big ET-1. There was no prepro-ET-1 mRNA in the cortex, except in the thickened precapillary arterioles present in only 30% of the aldosterone-producing adenomas studied. ET-1 immunoreactivity was detected in vascular structures (score, +), probably bound to receptors, suggesting that ET-1 has an endocrine action. The low concentrations of ET-1 could also indicate that it acts in a paracrine-autocrine fashion to control adrenal blood flow. The discrepancy between the concentrations of ECE-1 and its substrate suggests that ECE-1 has another role in the adrenal secretory cells. Our data indicate that ET probably is not a primary cause of the development or maintenance of the adenoma.

Adrenal Cortex↗
PubMed2004

Complete cDNA sequence and mRNA expression of dog preproendothelin-3.

The full-length cDNA of dog preproendothelin-3 (PPET3) was cloned from lung tissue using RT-PCR and rapid amplification of cDNA ends. Aside from the poly (A) tail, the full-length cDNA was 1976 bp. A polyadenylation signal sequence and one copy of a consensus sequence, ATTTA, which is related to mRNA turnover, was found in the 3' noncoding region. The cDNA had a 594-bp open reading frame encoding a 198-amino acid polypeptide. Regions corresponding to a bioactive mature ET3 peptide, an intermediate form known as big-ET3, and an ET3-like peptide were observed in dog PPET3. Expression of PPET3 mRNA was detected throughout the organs examined, which included heart, lung, liver, kidney, spleen, stomach, pancreas, duodenum, colon, uterus, ovary and testis.

Amino Acid Sequence↗
PubMed1985

An inexpensive apparatus for simultaneous automatic measurement of oxygen consumption in six small laboratory animals.

A closed-circuit system for the simultaneous measurement of oxygen consumption in six small laboratory animals is described. The system consisted of six glass chambers in a big water bath of constant temperature, an oxygen-supply unit, six pressure sensors, a microcomputer and a printer, or, optionally, a desk-top calculator. Ventilation within the chambers provided rapid equilibration of air temperature and humidity conditions. Easily sealing glass lids facilitated operation and maintenance of the system. Carbon dioxide was absorbed inside the chambers by soda lime. At 6-min intervals the consumed oxygen in each chamber was automatically replaced with oxygen from a low-pressure tank. The microcomputer, a self-constructed piece of equipment containing a Z 80 A central processing unit, received pressure data from the separately operating sensors, determined the decrements in chamber pressure due to oxygen consumption by the animal sitting in the chamber, and stored the calculated values in a 2 Kbyte RAM for outprint at the user's request. The apparatus proved to be sensitive, accurate, and easy to operate.

Animals↗
PubMed2005

Phylogenetic studies of pantherine cats (Felidae) based on multiple genes, with novel application of nuclear beta-fibrinogen intron 7 to carnivores.

The pantherine lineage of the cat family Felidae (order: Carnivora) includes five big cats of genus Panthera and a great many midsized cats known worldwide. Presumably because of their recent and rapid radiation, the evolutionary relationship among pantherines remains ambiguous. We provide an independent assessment of the evolutionary history of pantherine lineage using two complete mitochondrial (mt) genes (ND2 and ND4) and the nuclear beta-fibrinogen intron 7 gene, whose utility in carnivoran phylogeny was first explored. The available four mt (ND5, cytb, 12S, and 16SrRNA) and two nuclear (IRBP and TTR) sequence loci were also combined to reconstruct phylogeny of 14 closely related cat species. Our analyses of combined mt data (six genes; approximately 3750 bp) and combined mt and nuclear data (nine genes; approximately 6500 bp) obtained identical tree topologies, which were well-resolved and strongly supported for almost all nodes. Monophyly of Panthera genus in pantherine lineage was confirmed and interspecific affinities within this genus revealed a novel branching pattern, with P. tigris diverging first in Panthera genus, followed by P. onca, P. leo, and last two sister species P. pardus and P. uncia. In addition, close association of Neofelis nebulosa to Panthera, the phylogenetic redefinition of Otocolobus manul within the domestic cat group, and the relatedness of Acinonyx jubatus and Puma concolor were all important findings in the resulting phylogenies. The potential utilities of nine different genes for phylogenetic resolution of closely related pantherine species were also evaluated, with special interest in that of the novel nuclear beta-fibrinogen intron 7.

Animals↗
PubMed1995

Prognosis of and factors associated with dental status in the adult Swedish population, 1975-1989.

The aim was to describe changes in dental status in the Swedish population during the period 1975-89 and to make a prognosis based on these data for the year 2000. This study is based on investigations of the living conditions in 1975, 1977, 1980/81 and 1988/89 performed by The National Central Bureau of Statistics. The samples varied for each year from 11,500 to 15,000 participants and a response rate from 80 to 86%. The odontological questions of the interview were focused on dental status, utilization of dental services and chewing ability. The prevalence of edentulism in age group 16-74 yr decreased from 15% in 1975 to 6% in 1988/89. In 1988/89 19% of the 65-74-yr-old inhabitants of the big cities were edentulous and 45% in rural populations, indicating a 15-20-yr delay of the development in rural areas. The prognosis for the year 2000 indicates a further decrease of edentulism to 3-4% in age groups 45-64 yr and in age 75-84 yr more than 60% will be dentate. As a consequence of the reduction in edentulism and changes in populations the number of dentate inhabitants in age group 25-74 yr increased by about 800,000 from 1975 to 1989 and a further increase of 400,000 will occur up to the year 2000. The consequences of these changes for the dental care services are discussed.

Adolescent↗
PubMed1984

[Brain performance and behavior in senile dementias of the Alzheimer type].

Following a brief review of the recent literature on dementia methodological problems in the assessment of intellectual disturbances, psychopathological syndroms and modifications of behaviour in dementia are discussed. The study deals with the course of illness of untreated patients suffering from senile dementia of the Alzheimer's type. Patients were investigated five times during a period of 35 days. Scales used were the SKT-FPB test system (Erzigkeit, 1977), the Sandoz Clinical Assessment Geriatrics (SCAG, Shader et al., 1974) and the Geriatric Rating Scale (GRS, Plutchik et al., 1970). The first test system measures brain performance were the SCAG and the GRS mainly deal with psychopathological and behavioural disturbances. For resp. five factors of SCAG resp. GRS could be separated through hierarchical cluster analysis. No significant difference between the values of the SKT-FPP test system and the two observer rating scales could be found at any time of the study. This also proved right when dementias were separated clinically into mild and severe forms. These two groups could only be differentiated by the SKT-FPP test system, the factor 1 (organic impairment) of the SCAG and the factor 4 (social maladaption) of the GRS. Following a separation of clinically ameliorated, worsened or unchanged patients at the end of the study significant differences could only be found in the values of the FP-standard points and the factors organic impairment, depression and social maladaption in the observer rating scales. The impression, that prognosis of patients with a statistically unstabile course (descriptively assessed by means of the sum of variances) would be different from patients with stabile courses could not be proven. Investigation by correlation statistics of the whole patient groups at the test points showed that the FP-standard points correlated only with the factors social maladaption and organic impairment. It is concluded that according to this data best assessment of the course of illness is by psychometric methods, i.e. the SKT-FPB test system in this study. Observer rating scales, frequently mentioned in the literature seem to be more inconsistent and problematic for the valuation of the course of illness of dementias. They also seem to be in sufficient to evaluate effects of therapy, a fact being of major importance when concerning their frequent use in psychopharmacological trials in demented patients. The study could also show, that the variation in course of illness of patients suffering from senile dementia of the Alzheimer type is so big, that grouping these patients leads to the loss of statistical differences of their illness.

Aged↗
PubMed2006

Fragment-based drug design: how big is too big?

Much has been discussed about the proper physicochemical properties (e.g., molecular weight, hydrophobicity, etc.) that should be considered when utilizing fragment leads in drug design. However, little has been reported as to what emphasis, if any, should be placed on the potency of the resulting fragment leads. In this report, a retrospective analysis of 18 highly optimized inhibitors is described in which the compounds were systematically deconstructed until the minimal binding elements could be identified. An analysis of the potency changes that were observed as the leads were reduced in size indicate that a nearly linear relationship exists between molecular weight and binding affinity over the entire range of sizes and potencies represented in the dataset. On the basis of these observations, prediction maps can be constructed that enable critical and quantitative assessments of the process of lead identification and optimization. These data place well-defined limits on the ideal size and potency of fragment leads that are being considered for use in fragment-based drug design.

Drug Design↗
PubMed1994

AIDS: the unwelcome visitor.

AIDS beds are still hard to find outside of a few big cities, because operators are concerned that the stigma of the disease will cause them to lose staff members and geriatric residents. But as the epidemic worsens, more facilities will be expected to admit persons with AIDS. Caregivers who have begun to address the unique social and medical needs of this patient group have experienced satisfaction in helping those truly in need.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[The polymorphic BsuRI restriction site of the swine growth hormone gene].

Restriction fragment length polymorphism of the gene of the growth hormone was investigated in Big White and Mirgorod pigs. A polymorphous BsuRI restriction site was found within an amplified gene-region near 5-end. It was localized within the first intron, 1.6 b.p. higher than exon 2 was. Homozygous as well as heterozygous animals according to variants of the gene were found.

Alleles↗
PubMed2004

Spontaneous multiple mutations show both proximal spacing consistent with chronocoordinate events and alterations with p53-deficiency.

Analysis of spontaneous multiple mutations in normal and tumor cells may constrain hypotheses about the mechanisms responsible for multiple mutations and provide insight into the mutator phenotype. In a previous study, spontaneous doublets in Big Blue mice were dramatically more frequent than expected by chance and exhibited a mutation pattern similar to that observed for single mutations [Mutat. Res. 452 (2000) 219]. The spacing between mutations in doublets was generally closer than expected by chance and the distribution of mutation spacing fit an exponential, albeit with substantial scatter. We now analyze 2658 additional mutants and confirm that doublets are enhanced dramatically relative to chance expectation. The spacing, frequency and pattern of spontaneous doublets and multiplets (domuplets) are examined as a function of age, tissue type, p53-deficiency and neoplasia in the new and combined data. The new and combined data confirm that the distribution of the spacing between mutations in doublets is non-random with the mutations more closely spaced than expected by chance (P < 0.0005; combined data), consistent with temporally coordinate (chronocoordinate) events. An exponential provides an excellent fit to the distribution (R2 = 0.98) and estimates that half of doublets have mutations separated by 120 nucleotides or less (the "half-life of mutation spacing"). We make several novel observations: (i) singlets and doublets show similar overall increases in frequency with age (ii) doublet frequency may be lower in the male germline, consistent with the generally reduced mutation frequency in the male germline (iii) doublet frequencies are elevated in somatic tissues of p53-deficient mice (Li-Fraumini cancer syndrome model; P = 0.005) and (iv) doublets and singlets in tumors from p53-deficient mice have a different mutation pattern (P = 0.007). The observations are consistent with chronocoordinate occurrence of spontaneous doublets and multiplets due to a transient error-prone condition and do not suggest a major role for the recently discovered Y family of error-prone polymerases. The enhancement of doublets in p53-deficient mice may contribute to cancer risk.

Animals↗