Studies in the biochemistry of micro-organisms: The metabolic products of the Penicillium brevi-compactum series.
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Biomedical subjects
Publications and source records attributed to G Smith.
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In a previous preoperative study of patients with gliomas, we made the original observation that patients with high grade as opposed to those with low-grade gliomas have a psychological profile marked by extreme emotional reactivity. In this postoperative study of the psychological profiles of patients with breast cancer, the main funding was unexpectedly analogous with the findings in the brain tumour study. The patients with poorly differentiated ductal carcinomas showed a specific and, compared to the patients with well differentiated carcinomas, outstanding psychological profile marked by extreme emotional reactivity as well as by genuine creativity. Some of the present patients with well differentiated carcinomas showed personality profiles marked by compulsive inhibition, also described earlier in the literature of patients with breast cancer. The psychobiological relations between emotional reactivity and aggressiveness of tumour growth are discussed.
Double-blind administration of a single intramuscular dose of 1.5, 2.0, 2.5, or 3.0 mg levonantradol or placebo to 56 patients with moderate to severe postoperative or trauma pain showed significant analgesic effects of each dose of levonantradol as compared to placebo (P less than 0.05). However, no significant dose response was observed. Compared to 2/16 patients on placebo, 23/40 patients (57 per cent) on levonantradol reported one or more side effect. Drowsiness was most frequent. Dry mouth, dizziness, "weird dreams," mild hallucinations, nervousness, apprehension and confusion occurred less frequently. Changes in resting heart rate and blood pressure were minor and general acceptability was good.
The two functional domains of a cloned human fibroblast NADPH-cytochrome P450 reductase have been expressed in Escherichia coli and purified on the milligram scale for crystallization studies. One domain contains the cofactor FMN-binding site and the other contains the binding sites for cofactor FAD and substrate NADPH. Crystals of both domains have been obtained by the microbatch method. The crystals of the FMN domain belong to the monoclinic space group P21, with unit cell dimensions of a = 39.3 A, b = 51.5 A, c = 47.8 A, and beta = 105.7 degrees and have one molecule in the asymmetric unit. Diffraction data up to 2.3 A were collected with a merging residual on intensity of 9.3%. The crystals of the FAD/NADPH domain belong to the ortho-rhombic space group P212121 with unit cell dimensions of a = 55.9 A, b = 58.6 A, c = 131.1 A and have one molecule in the asymmetric unit. Diffraction data up to 2.6 A were collected with a merging residual on intensity of 8.0%.
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The role of platelet-activating factor (PAF) in human endotoxaemia was investigated by incubating human monocytes from 27 subjects with S. minnesota endotoxin in vitro. Monocytes synthesized 1.01 +/- 0.4 x 10(-10) M to 5.3 +/- 1.51 x 10(-9) M PAF after 60 min of incubation with endotoxin at concentrations of 1 x 10(-8) M and 4.5 x 10(-6) M respectively. The endotoxin-stimulated release of PAF was not significantly increased in monocytes cultured on a human endothelial cell monolayer. This rapid release of PAF in response to endotoxin is consistent with a role for monocyte-derived PAF as a toxic mediator of the acute systemic changes observed in patients with endotoxin-related septic shock.
Several animal models of AD have been developed, based upon the consistent finding of a presynaptic cholinergic deficit in AD. Significant cell loss in the NBM, the primary cortical cholinergic afferent, has been reported in AD. Lesions of the corresponding nuclei in the rodent and primate produce a persistent cholinergic deficit, but no consistent change in other neurotransmitter systems. Significant mnestic and cerebral metabolic deficits are observed acutely after lesion, which are responsive to pharmacological reversal and recover over time. Administration of AF64A produces similar mnestic and cholinergic deficits as NBM lesion, but these effects may be less responsive to pharmacological reversal. Administration of scopolamine, a muscarinic receptor antagonist, produces transient receptor blockade, mnestic deficits and deficits in cerebral metabolism, which can be reversed with a variety of pharmacological agents. The primary dissociations between these models and the deficits in AD are the lack of pharmacological response and recovery of function in AD patients and the presence of non-cholinergic neurochemical and cytoskeletal abnormalities. Future research should focus upon the systematic production and analysis of non-cholinergic neurotransmitter and cytoskeletal abnormalities to determine the contribution of these factors to the pathology seen in AD and the production of deficit in aged animals, which may more closely approximate the deficits in AD. The analysis of factors involved in recovery of function and pharmacological response in animal models may provide insight into potential treatment approaches to AD.
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From January 1994 through May 1995, Prudential HealthCare-North Texas prospectively studied 299 member patients diagnosed with hypercholesterolemia for whom pharmacotherapy with one of four 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, also known as statins, was prescribed. The purpose of this study was to measure the relative cost-effectiveness (CE) of these drugs in a real-world setting. This study provides information to assist decision makers in managed-care organizations (MCO) in making formulary selections. The study used a prospective, randomized, balanced cohort design, examining patients who had been prescribed initial therapy with a statin drug as monotherapy. Costs (direct medical and indirect costs) and effectiveness (percent reduction in low-density lipoprotein cholesterol levels) were based on approximately the first 6 months of initial therapy. Both the MCO and patient perspectives were considered. In the base case, mean CE ratios were significantly lower for fluvastatin compared with lovastatin, pravastatin, and simvastatin from both the managed-care perspective and the patient perspective. Sensitivity analysis did not alter the CE conclusions, even under conditions of varying cost structures. Although differences were found in the effectiveness of lovastatin, pravastatin, and simvastatin measured in this study versus efficacy measured for these drugs in controlled clinical trials, sensitivity analysis suggests that these differences alone do not determine the superior CE of fluvastatin. Finally, this study supports the idea that well-designed formularies should consider drug CE (based on safety, effectiveness, and cost) and that integration of the pharmacy benefit management with other medical management is essential. These results provide evidence that fluvastatin may represent a more cost-effective formulary choice among statin products used for initial monotherapy of hypercholesterolemia.
Every day there are 6000-7000 papers published in science. Since the C-L psychiatrist may be asked to consult on a patient with any medical illness, and who may be on any medical drug, methods need to be developed to review the recent literature and have an awareness of current findings. At the same time, teachers need to develop a current listing of seminal papers for trainees and practitioners of this subspecialty of psychiatry. Experts chosen because of their writings and acknowledged contributions to their subspecialty interests have sifted through thousands of articles to select the ones they regard as the most important for trainees in C-L psychiatry. In addition, certain countries--Spain, Portugal, Germany, Mexico, Australia and Brazil are developing national databases of C-L literature not only for their own use, but also to bring them to the attention of other parts of the world. This fifth iteration of the C-L literature database has especially targeted the period of 1996-1999--the millennium issue--in order to have easier access to contemporary essential studies on common problems. Part II of this issue describes the seminal cardiac drug-psychotropic drug interactions that the C-L psychiatrist may encounter in the most common medical disease in the United States--coronary heart disease--with advise to the practitioner as to their management. The use of the Internet and institutional Intranets is described.
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A new variant of blood group A, termed Apae, was found as an inherited characteristic in three unrelated white families. Apae was distinguished from other A variants by its agglutination and absorption-elution reactions with only certain human anti-A and -A,B serums, by the red cells that reacted with anti-A from Helix pomatia without the need for enzyme treatment, by enhancement of the latter reaction with bromelinization, and by the presence in the serum of an anti-A of normal avidity and titer. Apae also reacted strongly with a recently discovered anti-A agglutinin derived from the seaweed Codium fragile, subspecies atlanticum, but not with a series of other anti-A lectins. It was concluded that Apae cells express only part of the normal A antigen and that the anti-A present in the serum does not have an anti-Apae component.
David P. Phillips has reported evidence that famous people are often able to postpone their deaths until after a birthday. A reexamination of Phillips' data shows some aspects of his analysis to be questionable, including the lumping together of deaths that occur during the birthmonth, which does not distinguish deaths that occurred before the birthday from those that occurred afterward. A reanalysis of his data shows that there were actually a relatively large number of deaths in the month preceding and the months following the birthday. One explanation is that the anxiety associated with this milestone and the excesses associated with its celebration are sometimes fatal. Another explanation is that Phillips' results were a fluke created by a selective use of data.
Earlier studies reported a decline in September mortality in New York City and Budapest during years when Yom Kippur was in the interval September 28 through October 3, and fewer deaths among Californians with Jewish surnames during the week preceding Passover than during the week after Passover. These studies suggest that some Jews are able to postpone their deaths until after the celebration of an important religious event. We reexamine these findings using new data and find no statistically persuasive evidence that Jewish deaths decline before religious holidays. We do find an increase in deaths in the weeks shortly before and after birthdays.
Expressed sequence tags (ESTs) provide a rapid and reliable method for gene discovery as well as a resource for the large-scale analysis of gene expression of known and unknown genes. Here we describe a normalized cDNA library developed from a 10-day-old White Leghorn chicken whole embryo. The utility of the library was evaluated by partial sequencing of 99 randomly selected insert-containing clones and the analysis of EST-targeted genomic regions for single nucleotide polymorphisms (SNPs) in the East Lansing chicken reference DNA mapping panel. Using stringent match criteria of percent identity of 80 or higher across a length of 50 or more bases, 46 ESTs matched database sequences including previously reported Gallus gallus genes. Thirty-seven of the 50 primer pairs developed from 50 unique ESTs amplified a single fragment. The size of the 37 amplicons ranged from 276 to 693 bp for a total of 17,508 and an average of 473. About 70% of the SNPs detected were either G-->A or C-->T transition. The number of SNPs detected within the amplicons from EST-targeted genomic regions ranged from 0 to 4 for a total of 65 and a frequency of about 1 every 470 bases. About 35% of the amplicons contained only 1 SNP, while 19% had 4 SNPs. Using the SNPs that were informative in the East Lansing reference panel, 17 ESTs were mapped on the East Lansing chicken genetic map. The ESTs described, as well as the nucleotide variants identified within the EST-targeted genomic regions, represent significant resources for genome analysis in the chicken.
Deficiency of the adult corpus callosum in BALB/c mice shows incomplete penetrance and is clearly polygenic, whereas the defect in fetuses shows complete penetrance and a much less complex mode of inheritance. Retardation of the growth of the corpus callosum and the hippocampal commissure in the fetal mouse forebrain was expressed by a standard score (z) derived from body weight, such that a fetus with a score less than -2.0 was held to have commissures abnormally small for the body size. By this index, almost all C57BL/6 fetuses were normal, whereas BALB/c fetuses in the body weight range 0.5 to 1.0 g were often 5 standard deviations below the expected value of 0.0. In classical crosses between C57BL/6J and BALB/cWah, inheritance of the index of abnormality (z) was recessive, and about half of the fetuses in backcrosses to BALB/c were below -2.0. However, the distribution of scores was not bimodal. The results were consistent with a two-locus but not a single-locus difference between parent strains. Among the seven recombinant inbred strains derived from the By strains of C57BL/6 and BALB/c, there were three or possibly four distinct clusters of strains, which also suggested two-locus inheritance and excluded a single-locus difference. Although substantial retardation of commissure growth was evident in fetuses, deficiency or absence of the corpus callosum in weanling and adult By recombinant inbred mice was extremely rare in all strains except BALB/cByJ. These data confirm anatomical results showing that, in all but the most extremely retarded cases, the corpus callosum recovers from an obvious prenatal defect.
Nurses in home healthcare and hospice are embracing the advances in computer science and technology to provide an edge in administration and clinical practice. Of concern to nurse managers is the extent to which personal computers and the Internet have been used in home healthcare and hospice, and what information, opportunities, and needs related to education are on the horizon. This article discusses the results of a national survey conducted exclusively on the World Wide Web to answer these questions.