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PubMed2004

A seven-membered aluminum sulfur allenyl heterocycle arising from the conversion of an aluminacyclopropene with CS2.

The reaction of an aluminacyclopropene LAl[eta2-C2(SiMe3)2] (1, L = HC(CMeNAr)2, Ar = 2,6-iPr2C6H3) with CS2 in the temperature range from -78 degrees C to room temperature affords the first seven-membered aluminum sulfur-containing heterocyclic compound [LAl]2(mu-S)[eta2-SC(SiMe3)=C=C(SiMe3)] (2) bearing an allenyl group. The structural characterization of 2 and the analogous compound LAl[OC(O)C2(SiMe3)2] (3) of the proposed intermediate A and the variable-temperature 1H NMR kinetic study of this reaction may give a better understanding on this unusual conversion.

Aluminum↗
PubMed1996

Lewis Acid-Promoted, Stereocontrolled, Gram Scale, Diels-Alder Cycloadditions of Electronically Matched 2-Pyrones and Vinyl Ethers: The Critical Importance of Molecular Sieves and the Temperature of Titanium Coordination with the Pyrone.

(R)-(+)-Binol-titanium coordinates with commercial methyl 2-pyrone-3-carboxylate and promotes mild, highly enantiocontrolled Diels-Alder cycloadditions with electron-rich vinyl ether CH(2)=CHOCH(2)-1-naphthyl and vinyl silyl ether CH(2)=CHOSiMe(2)Bu-t leading to valuable 1alpha,25-dihydroxyvitamin D(3) (calcitriol) intermediate (-)-2. Unexpectedly, two subtle variables were found to be critical for obtaining reproducibly over 90% enantioselectivities in gram scale cycloadditions: (1) the moisture content (15-17% is best) of the molecular sieves used to prepare the binol-titanium complex according to the Mikami protocol and (2) the temperature (50 degrees C is best) at which the pyrone ester is mixed with the binol-titanium complex. Unsubstituted 2-pyrone undergoes ytterbium-promoted, high-pressure, regioselective, and stereoselective Diels-Alder cycloaddition with benzyl vinyl ether to form versatile bicyclic lactone (+/-)-4 on gram scale.

Journal Article↗
PubMed2000

Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: an outcome-oriented decision analysis.

Two treatments are accepted for patients with solitary hepatocellular carcinoma </=5 cm in size and with preserved hepatic function: (1) liver resection, which can be performed without delay but has a high recurrence rate, and (2) liver transplantation, which has a better long-term survival, but is not easily available because grafts are scarce. A third possibility is to offer liver resection first and liver transplantation for tumor recurrence or deteriorating liver function ("salvage" transplantation). We investigated the implications of such a strategy with a Markov-based decision analytic model. In a scenario assuming intermediate values for 4 main variables (12-month waiting list; tumor progression outside transplantation criteria: 4% per month; recurrence after resection: 20% per year; recurrences eligible for transplantation: 60%), the life expectancy was 8.8 years for primary transplantation versus 7.8 years for primary resection and salvage transplantation, with a calculated use of grafts at 5 years of 52% for primary transplantation versus 23% for salvage transplantation. This study estimates of the survival and graft-saving of a strategy of primary resection and salvage transplantation according to variables that are to some extent predictable. This strategy may be a rational way to cope with lengthening waiting lists, especially for patients with tumors close to the limit for transplantation criteria, if the results of liver resection are good, if patients with the lowest risks of recurrence can be selected, and if a strict follow-up can detect recurrences when the patients are still transplantable.

Carcinoma, Hepatocellular↗
PubMed1985

Human prolactin heterogeneity in pituitary effluent blood.

We have used column chromatography to study prolactin (PRL) heterogeneity in plasma obtained from the inferior petrosal vein, a sampling site very close to the anterior pituitary gland. Blood specimens were obtained from four hyperprolactinemic subjects over varying time intervals during inferior petrosal vein venography. All patients demonstrated an increase in PRL secretion during the sampling period which was presumably secondary to the mild stress of the procedure. In each study subject there was an increase in the percent and amount of PRL secreted as small PRL (peak III) as the PRL concentration in the inferior petrosal vein increased to a maximum. The percent secreted as intermediate PRL (peak II) fell while the amount either remained constant or increased slightly. The percent and amount eluting as large PRL (peak I) was small and unchanging in patients 1, 2 and 3, despite the increase in total PRL concentration. Patient 4 had an unusual elution pattern in which the 0 minute specimen contained predominantly large PRL. As the total PRL concentration increased the percent and amount eluting as small PRL dramatically increased while the percent eluting as large PRL fell in proportion to the increase of small PRL. Intermediate PRL was virtually absent in this patient. Thus, this study indicates that the increase in PRL concentration during a secretory pulse is primarily from small PRL while the contributions of large and intermediate PRL are modest and variable.

Adult↗
PubMed2000

Feasibility and accuracy of left ventricular volumes and ejection fraction determination by fundamental, tissue harmonic, and intravenous contrast imaging in difficult-to-image patients.

The need to enhance the echocardiographic determination of left ventricular ejection fraction is greatest in patients with suboptimal images. Intravenous contrast (CON) and tissue harmonic imaging (THI) are 2 important methods for enhancing endocardial border definition. However, the comparative feasibility and accuracy of THI and contrast-enhanced power harmonic imaging in difficult-to-image patients have not been examined. We assessed the comparative accuracy of THI and CON in determining EF and ventricular volumes in patients with suboptimal fundamental images. We demonstrated that CON is feasible and exhibits a greater correlation with ejection fraction and ventricular volumes determined by radionuclide angiography (standard of comparison) than THI in this difficult-to-image population, with no reported side effects. For both ejection fraction and ventricular volumes, the observer variability was least for CON, intermediate with THI, and greatest for fundamental imaging.

Adult↗
PubMed1974

Quasilinkage equilibrium and the evolution of two-locus systems.

In terms of intrinsic variables of the system, short, intermediate, transitional, and long (or asymptotic) times are defined for the evolution of a two-locus model with linkage and epistasis. It is argued that, during the first two and last periods, all quantities of genetic interest, such as the gametic frequencies, the mean fitness, the linkage disequilibrium, and the linkage disequilibrium ratio, Z, change with time in essentially the same manner, characteristic of the particular epoch concerned and determined in this paper, and therefore, when quasilinkage equilibrium occurs, it is a transitional phenomenon. Both continuous random births and deaths and discrete, nonoverlapping generations are considered.

Diploidy↗
PubMed1986

A DNA insertion/deletion necessitates an aberrant RNA splice accounting for a mu heavy chain disease protein.

The human heavy chain disease protein BW is an immunoglobulin mu-chain variant whose amino terminus is initiated at the fifth amino acid of the first constant region domain. We cloned and analyzed both rearranged heavy chain alleles from BW leukemic cells to determine the molecular basis for this deleted protein. The phenotypically excluded heavy-chain allele possessed two intermediate recombinations of separate variable-diversity (V-D) and diversity-joining (D-J) junctions, neither of which were expressed. The productive allele, responsible for the mu chain, had a complete V-D-J4 recombination but as a result of a single-base deletion possessed stop codons within the variable region. More important, a small DNA insertion/deletion eliminated the J4 donor splice site. This necessitated an aberrant RNA splice between the leader region and the first constant region domain creating a shortened 2.35-kilobase muRNA. A recognition sequence for signal peptidase predicted a cleavage at the fifth amino acid of the first constant region domain. These molecular events are responsible for the truncated mu chain that lacks a variable region and fails to assemble light chains.

Alleles↗
PubMed1997

Inheritance and mapping of Compact (Cmpt), a new mutation causing hypermuscularity in mice.

During selection for protein content in mice at the Technical University of Berlin, individuals showing high protein content and a compact exterior were noted. Animals showing this "Compact" phenotype were separated to form a new line. The present investigations were carried out on a Hungarian subpopulation of this line, selected for maximum expression of the Compact phenotype, and apparently at fixation for the relevant genes. Fertility and viability of the Compact subpopulation was normal. As compared to normal mice, carcass percentage values for male and female Compact mice were 9.4 and 6.8% greater, respectively; and the muscle:bone weight ratio in males was 1.61-fold greater. The Compact phenotype showed variable expressivity and was of intermediate dominance in males, but almost fully recessive in females. The hypothesis that a single gene is solely responsible for the Compact phenotype was rejected by maximum likelihood analysis. Linkage mapping using selective DNA pooling located a single locus (denoted Cmpt) strongly associated with the Compact phenotype on mouse chromosome 1. Fine mapping, using individual selective genotyping and haplotype analysis, located Cmpt to the region between D1Mit375 and D1Mit21, approximately one third of the way to D1Mit21.

Animals↗
PubMed1994

Melanocytic nevi in children. I. Anatomic sites and demographic and host factors.

A survey of benign melanocytic nevi was conducted among schoolchildren in Perth, Western Australia, in 1985, with the aim of describing the prevalence and causes of nevi. Children were recruited from Perth public schools that were chosen to be representative of the socioeconomic and geographic distribution of the population. Of 4,898 eligible children, 2,595 (53%) had all of their nevi counted by one member of a team of five nurses. Analysis was restricted to 2,552 children aged 5-14 years. Children of European origin (i.e., white children), who comprised the majority of the sample (2,376 children), had many more nevi than did children of other ethnic origins. Among white children, the prevalence of nevi increased progressively with age, although the number of nevi per unit of skin area reached a plateau at about 9 years of age. Boys had more nevi at all ages than did girls. The number of nevi per unit of area was highest on the lateral surfaces of the upper limbs and the face and neck, and was lowest on the lower limbs. Children whose parents had been born in Southern Europe were likely to have few nevi. Children with red hair had relatively few nevi, but children with light skin generally had more nevi than children with darker skin. Ability to tan and propensity to burn were also associated with number of nevi, although not in a simple fashion; numbers of nevi were highest in intermediate categories of these two variables. The relation with freckling was also complex; the mean number of nevi increased with increasing freckling until the freckling became moderate to heavy, after which it fell.

Adolescent↗
PubMed1998

Confidence in life-support decisions in the intensive care unit: a survey of healthcare workers. Canadian Critical Care Trials Group.

OBJECTIVE: To examine the relationship between intensive care unit (ICU) healthcare workers' confidence and their decision to withdraw life support. DESIGN: Cross-sectional survey of Canadian intensivists, ICU housestaff, and bedside nurses. Respondents chose the level of care (from comfort measures only to full aggressive care) for 12 patients described in clinical scenarios, and rated their confidence in their decisions. SETTING: Thirty-seven Canadian university-affiliated hospitals. PATIENTS: None. INTERVENTIONS: We used discrete data analysis models to examine the association between the chosen level of care, confidence in the decisions, the clinical scenario, and healthcare worker group. MEASUREMENTS AND MAIN RESULTS: The response rate was 1,361 (76%)/1,795; for this analysis, we used data from 1,306 respondents with completed questionnaires. Responses for each scenario varied widely among respondents. The level of care chosen was dependent on the scenario, the healthcare worker group, and the confidence with which the decisions were made (p < .001 for each). Intensivists were less aggressive than the ICU nurses, who were less aggressive than the housestaff, but the magnitude of effect was small. Overall, respondents were very confident about their decisions 34% of the time. After adjustment for clinical scenario and chosen level of care, intensivists were more confident than nurses, who were more confident than housestaff (40% of intensivists, 29% of nurses, and 23% of housestaff were very confident). In general, healthcare workers tended to be more confident when they chose extreme levels of care than when they chose intermediate levels of care. Considerable variability in responses to scenarios remained even when we considered only those responses made with the highest level of confidence. CONCLUSIONS: While confidence in decisions about withdrawal of life support increases with seniority and authority, consistency of decisions may not. When given standard information, healthcare workers can make contradictory decisions yet still be very confident about the level of care they would administer.

Aged↗
PubMed2004

Locomotion in bonobos (Pan paniscus): differences and similarities between bipedal and quadrupedal terrestrial walking, and a comparison with other locomotor modes.

One of the great ongoing debates in palaeo-anthropology is when, and how, hominids acquired habitual bipedal locomotion. The newly adopted bipedal gait and the ancestral quadrupedal gait are most often considered as very distinct, with each habitual locomotor mode showing corresponding anatomical adaptations. Bonobos (Pan paniscus), along with common chimpanzees (P. troglodytes), are the closest living relatives to humans and their locomotion is valuable for comparison with other primates, and to gain an insight in the acquisition of human bipedalism. Bonobos are habitual quadrupeds, but they also engage in bipedal locomotion, both on terrestrial and in arboreal substrates. In terms of kinematics and dynamics, the contrast between bipedal and quadrupedal walking seems to be more subtle than one might expect. Apart from the trunk being approximately 37 degrees more erect during bipedal locomotion, the leg movements are rather similar. Apart from the heel, plantar pressure distributions show subtle differences between bipedal and quadrupedal locomotion. Regardless, variability is high, and various intermediate forms of locomotion (e.g. tripedal walking) exist both in captivity and in the wild. Moreover, there is overlap between the characteristics of walking and other locomotor modes, as we show with new data of walking on an inclined pole and of vertical squat jumps. We suggest that there is great overlap between the many locomotor modes in bonobos, and that the required polyvalence is reflected in their anatomy. This may hamper the development of one highly specialized gait (i.e. bipedalism), which would constrain performance of the other types of locomotion.

Animals↗
PubMed1996

c-erbB-2/neu protein expression, DNA ploidy and S phase in breast cancer.

DNA content and c-erbB2/neu protein (p185) expression were evaluated by flow-cytometry and ELISA, respectively, in 166 specimens of primary breast cancer. A non-diploid DNA content was found in 88 tumours (53%), with the DNA index ranging from 0.7-2.7. S phase fraction (SPF) evaluation, performed in 130 cases, showed significantly higher values in aneuploid than in diploid tumours (median values, 17.3% and 5.8%, respectively). Thirty-six tumours (21.6%) showed p185 overexpression, while 45 (27.1%) and 85 (51.3%) showed intermediate and low expression, respectively. A good correlation (P = 0.0023) was found between DNA content and p185 positivity. Tumours with high p185 values were mainly aneuploid, while tumours with intermediate or low expression had variable degrees of DNA content. Furthermore, p185 concentration was significantly higher in aneuploid than in diploid tumours (P = 0.009). The highest rate of p185 (+) cases and the highest p185 concentrations occurred in triploid (1.3 < D.I. < or = 1.7), compared to the other tumours. SPF values and p185 positivity rates were not significantly correlated in diploid and in aneuploid tumours.

Adult↗
PubMed1991

An in vitro model showing different rates of substrate cycle for phosphofructokinases of Escherichia coli with different kinetic properties.

An in vitro assay model is introduced for the coupled assay of phosphofructokinase (PFK) and fructose-bisphosphatase. The model is applied to the study of three PFK of Escherichia coli: two isoenzymes, phosphofructokinase-1 (PFK-1) and phosphofructokinase-2 (PFK-2), and a mutant form of phosphofructokinase-2 (PFK-2*). Results show that for a variety of conditions the PFK-1/fructose-bisphosphatase pair gives the lowest and the PFK-2*/fructose-bisphosphatase pair the highest rates of substrate cycle, with the PFK-2/fructose-bisphosphatase pair in an intermediate position. The effects of variables such as maximum activity ratios and MgATP concentration were explored. The possible role of MgATP in decreasing the futile cycle of the PFK-2/fructose-bisphosphatase pair is described. The results are discussed in terms of possible metabolic consequences of PFK-2* and of predictions of the model to be tested in vivo.

Adenosine Triphosphate↗
PubMed1984

Effects of maternal cigarette smoking on fetal trunk movements, fetal breathing movements and the fetal heart rate.

The acute effect of maternal cigarette smoking was studied in 10 patients between 37 and 40 weeks gestation. There was a significant reduction in the percentage of time the fetus spent moving during the first 16 min of smoking (P less than 0.02). No significant changes were seen in the proportion of time the fetus spent breathing or the number of times the fetus changed from high or intermediate to low heart period variability. There were significant reductions in the number of accelerations (P less than 0.01), beat-to-beat variation (P less than 0.01) and root-mean-square of the deviation around the mean (P less than 0.02).

Adult↗
PubMed2006

Candidate gene studies in the 21st century: meta-analysis, mediation, moderation.

The results of a large body of candidate gene studies of behavioural and psychiatric phenotypes have been largely inconclusive, with most findings failing to replicate reliably. A variety of approaches that augment the 'traditional' candidate gene approach are discussed, including the use of meta-analysis to combine findings from existing published reports, the investigation of mediating variables (including the use of intermediate phenotypes or endophenotypes) and the awareness of possible moderating influences (such as sex or ethnicity) and gene-environment interactions on genetic associations, possibly via epigenetic mechanisms. Advances in genotyping technology will also allow the routine use of haplotype analysis and linkage disequilibrium mapping. Examples of how these approaches may improve our understanding of how genetic associations with behavioural and psychiatric phenotypes obtain are given.

Behavior↗
PubMedDate not supplied

Scratch cytologic findings on surgically resected solitary fibrous tumors of the pleura.

OBJECTIVE: To ascertain the cytologic characteristics of solitary fibrous tumors of the pleura (SFTPs) on smear preparations. STUDY DESIGN: Fine needle aspiration cytology (FNAC) was initially attempted preoperatively in five cases, but the specimens were inappropriate for interpretation because only a few tumor cells were obtained. Therefore, scratch smears made at the time of operation were used. Papanicolaou and immunocytochemical staining was performed in all 10 cases, 2 of which were malignant. RESULTS: As expected, cellular tumors yielded more cells. The cytologic appearance was variable, showing spindle/bipolar, dendritic/stellate and intermediate cells. Atypical cells reminiscent of sarcoma were also present in cellular, benign tumors. Highly atypical epithelioid cells were obtained in two malignant cases. Immunocytochemically, the tumor cells were positive for CD34 and vimentin and negative for cytokeratin, regardless of histologic differences and cell shape. CONCLUSION: It seems difficult to diagnose SFTPs with certainty by FNAC, partly because the cell morphology of SFTPs resembles a wide variety of heterogeneous groups of spindle cell tumors and partly because only a few tumor cells were available in the FNAC specimens in the present study. However, a cytologic diagnosis of SFTP is possible if cytologic preparations yield CD34-positive cells with spindle/bipolar or dendritic/stellate morphology.

Adult↗
PubMedDate not supplied

Phenotypic effects of apolipoprotein structural variation on lipid profiles. III. Contribution of apolipoprotein E phenotype to prediction of total cholesterol, apolipoprotein B, and low density lipoprotein cholesterol in the healthy women study.

The apolipoprotein (apo) E structural locus has been shown to influence concentrations of total cholesterol, apo B, and low density lipoprotein (LDL) cholesterol in population studies. Apo E has six phenotypes resulting from three common alleles at this locus. In the present study, we have typed 473 healthy white women for apo E. At baseline in 1984, all women were premenopausal. To date, 109 of these women have become postmenopausal and are not on hormone therapy. Statistical analyses were done on both pre- and postmenopausal groups to assess the influence of menopausal status in combination with the apo E locus on lipid profile. Nine lipoprotein lipids and apolipoproteins were categorized by three apo E phenotypes: apo E3-2, apo E3-3, and apo E4-3. These were compared in analysis of variance. At baseline, the apo E3-2 phenotype showed the lowest average concentrations of total cholesterol (170 mg/dl), apo B (80 mg/dl), and LDL cholesterol (91 mg/dl), while the apo E4-3 phenotype demonstrated the highest average concentrations of total cholesterol (192 mg/dl), apo B (104 mg/dl), and LDL cholesterol (116 mg/dl) (p less than or equal to 0.0004). Apo E3-3 homozygotes were intermediate on all three quantitative variables. The postmenopausal subset showed the same trends by phenotype, with overall increases in total cholesterol, apo B, LDL cholesterol, and triglycerides, regardless of phenotype. Women who remained premenopausal generally showed smaller increases in these same measures. Our results suggest that, on average, the lower lipoprotein values for the apo E3-2 phenotype are maintained through early menopause despite a worsening of lipid profiles for all women as they age.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed2006

Influence of overweight on surgical complications for gastric cancer: results from a randomized control trial comparing D2 and extended para-aortic D3 lymphadenectomy (JCOG9501).

BACKGROUND: The impact of overweight on the outcome of gastrectomy with lymphadenectomy is controversial, and data from a well-controlled, randomized study are needed to identify a possible relationship. METHODS: We used data from 523 patients registered for a prospective randomized trial comparing D2 and extended para-aortic D3 lymphadenectomy to compare the effects of body mass index (BMI) and the extent of lymphadenectomy for the development of general or major surgical complications (anastomotic leakage, abdominal abscess, and pancreatic fistula). RESULTS: Seventy-seven patients were classified as overweight with BMI >or= 25, and 38 and 39 of these patients underwent a D2 or D3 lymphadenectomy, respectively. Among the 446 patients classified as nonoverweight with BMI < 25, 225 received D2 and 221 received D3 lymphadenectomy. Surgical complications, operation time, and blood loss were statistically significantly associated with BMI, and logistic regression analysis revealed that overweight directly affected the occurrence of surgical complications even after considering operation time and blood loss as intermediate factors instead of outcome variables. Among patients undergoing D2 lymphadenectomy, being overweight increased the risk for surgical complications and blood loss, whereas overweight was associated with only blood loss and operation time among patients receiving D3 lymphadenectomy. CONCLUSIONS: Overweight increased the risk of surgical complications in patients undergoing gastrectomy both directly and indirectly through operation time and blood loss. The impact of overweight on surgical complications was more evident in patients undergoing a D2 dissection.

Aged↗