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Observed Affect

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100181. If Taken 1 Hour before Indinavir (IDV), Didanosine Does Not Affect IDV Exposure, despite Persistent Buffering Effects Full Text available with Trip Pro

If Taken 1 Hour before Indinavir (IDV), Didanosine Does Not Affect IDV Exposure, despite Persistent Buffering Effects Concurrent administration of indinavir and didanosine significantly reduces the level of exposure to indinavir, but it is unclear how soon after didanosine administration indinavir may be given safely. We compared indinavir pharmacokinetics and gastric pH in 12 human immunodeficiency virus-positive patients by use of 800 mg of indinavir alone versus 800 mg of indinavir (...) administered 1 h after didanosine administration. Median gastric pH was significantly higher when indinavir was taken after didanosine administration; however, no significant difference in the maximum concentration in plasma or the area under the concentration-time curve from time zero to 8 h was observed. Indinavir may be taken with a light meal 1 h following the administration of 400 mg of didanosine.

2001 Antimicrobial Agents and Chemotherapy

100182. A Novel Syndrome Affecting Multiple Mitochondrial Functions, Located by Microcell-Mediated Transfer to Chromosome 2p14-2p13 Full Text available with Trip Pro

A Novel Syndrome Affecting Multiple Mitochondrial Functions, Located by Microcell-Mediated Transfer to Chromosome 2p14-2p13 We have studied cultured skin fibroblasts from three siblings and one unrelated individual, all of whom had fatal mitochondrial disease manifesting soon after birth. After incubation with 1 mM glucose, these four cell strains exhibited lactate/pyruvate ratios that were six times greater than those of controls. On further analysis, enzymatic activities of the pyruvate (...) of microcell-mediated chromosome-fusion was performed between the present study's fibroblasts (recipients) and a panel of A9 mouse:human hybrids (donors) developed by Cuthbert et al. (1995). Complementation was observed between the recipient cells from both families and the mouse:human hybrid clone carrying human chromosome 2. These results indicate that the underlying defect in our patients is under the control of a nuclear gene, the locus of which is on chromosome 2. A 5-cM interval has been identified

2001 American Journal of Human Genetics

100183. Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain. Full Text available with Trip Pro

Putative mechanisms of action of antidepressant drugs in affective and anxiety disorders and pain. An enhancement of neurotransmission of serotonin (5-HT), noradrenaline, or both, underlies the antidepressant response associated with most agents presently available to treat major depression. With respect to the 5-HT system, antidepressant drugs exert immediate effects on some neuronal elements controlling overall transmission, but it is the gradual changes in neuronal responses (...) in various brain structures of laboratory animals are fully consistent with the conditions in the clinic necessary to attenuate symptoms in depression and OCD. It is also possible that the relief of chronic pain produced by some antidepressants may be mediated, in part, by the blockade of peripheral 5-HT2A receptors. These observations emphasize the notion that the 5-HT system is endowed with different adaptive properties in various parts of the body, which, in addition to the multiplicity of 5-HT

2001 Journal of Psychiatry and Neuroscience

100184. Does type of health insurance affect health care use and assessments of care among the privately insured? Full Text available with Trip Pro

Does type of health insurance affect health care use and assessments of care among the privately insured? To inform the debate about managed care by examining how different types of private insurance-indemnity insurance, PPOs, open model HMOs, and closed model HMOs-affect the use of health services and consumer assessments of care.The 1996-1997 Community Tracking Study Household Survey, a nationally representative telephone survey of households, and the Community Tracking Study Insurance (...) assessments of care include unmet or delayed care needs, satisfaction with health care, ratings of the last physician visit, and trust in physicians. Estimates are adjusted to control for differences in individual characteristics and location.As one moves from indemnity insurance to PPOs to open model HMOs to closed model HMOs, use of primary care increases modestly but use of specialists is reduced. Few differences are observed in other areas of service use, such as preventive care, hospital use

2000 Health Services Research

100185. Ahl2, a Second Locus Affecting Age-Related Hearing Loss in Mice Full Text available with Trip Pro

Ahl2, a Second Locus Affecting Age-Related Hearing Loss in Mice Inbred mouse strains with age-related hearing loss (AHL) provide valuable models for studying the genetic basis of human presbycusis. Here we report the genetic mapping of a second AHL locus in mice (designated Ahl2) that is a major contributor to the 8- to 10-month difference in hearing loss onset times between NOD/LtJ and C57BL/6J mice. A whole-genome linkage scan of 110 progeny from a (C57BL/6JxNOD/LtJ)xNOD/LtJ backcross (...) 10, showed that the hearing loss attributable to Ahl2 is dependent on a predisposing Ahl genotype. The statistically significant effect of Ahl2 observed in crosses with NOD/LtJ was not seen in crosses involving three other strains with early onset AHL: A/J, BUB/BnJ, and SKH2/J.

2002 Genomics

100186. A genetic interpretation of heightened risk of BSE in offspring of affected dams. Full Text available with Trip Pro

A genetic interpretation of heightened risk of BSE in offspring of affected dams. An analysis is presented of the results of a cohort study designed to test whether or not the aetiological agent of bovine spongiform encephalopathy (BSE) in cattle can be transmitted maternally (vertically) from dam offspring. Various genetic models are fitted to the data under the assumption that the results could be explained entirely by genetic predisposition to disease (as opposed to maternal transmission (...) ) given exposure of offspring of diseased and unaffected dams to contaminated cattle feed. The analyses suggest that the results could be explained by the hypothesis of genetic predisposition, provided a large difference exists in the susceptibility of resistant and susceptible hosts, and explore the range of genotypic parameters and frequencies consistent with the limited currently available data. The results presented are broadly robust, even under the scenario that a portion of the observed

1997 Proceedings of the Royal Society B: Biological Sciences

100187. Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series. Full Text available with Trip Pro

results from a series of 30 new pedigrees (259 individuals) genotyped for 13 polymorphic markers spanning chromosome 18. Subjects were interviewed by a psychiatrist and were diagnosed by highly reliable methods. Genotypes were generated with automated technology and were scored blind to phenotype. Affected sib pairs showed excess allele sharing at the 18q markers D18S541 and D18S38. A parent-of-origin effect was observed, but it was not consistently paternal. No robust evidence of linkage was detected (...) Linkage of bipolar affective disorder to chromosome 18 markers in a new pedigree series. Several groups have reported evidence suggesting linkage of bipolar affective disorder (BPAD) to chromosome 18. We have reported data from 28 pedigrees that showed linkage to marker loci on 18p and to loci 40 cM distant on 18q. Most of the linkage evidence derived from families with affected phenotypes in only the paternal lineage and from marker alleles transmitted on the paternal chromosome. We now report

1997 American Journal of Human Genetics

100188. A CR1 polymorphism associated with constitutive erythrocyte CR1 levels affects binding to C4b but not C3b Full Text available with Trip Pro

A CR1 polymorphism associated with constitutive erythrocyte CR1 levels affects binding to C4b but not C3b The erythrocyte type one complement receptor (E-CR1) mediates erythrocyte binding of complement-opsonized immune complexes (IC), and helps protect against random deposition of circulating IC. Two linked CR1 polymorphisms occur in binding domains, at I643T and Q981H. In Caucasians, the variant alleles (643T, 981H) are associated with low constitutive E-CR1 expression levels. This study (...) was conducted to determine if these polymorphisms affect ligand binding, and if so, represent risk factors for the autoimmune IC disease, systemic lupus erythematosus (SLE). In an ELISA comparing relative ligand binding differences, E-CR1 from individuals homozygous for the variant residues (643TT/981HH) exhibited greater binding to C4b, but not C3b, than homozygous wild-type E-CR1. Analysis of single-binding domain CR1 constructs demonstrated that the 981H residue imparted this enhanced C4b binding

2003 Immunology

100189. Transfer RNA modifications that alter +1 frameshifting in general fail to affect −1 frameshifting Full Text available with Trip Pro

Transfer RNA modifications that alter +1 frameshifting in general fail to affect −1 frameshifting Using mutants (tgt, mnmA(asuE, trmU), mnmE(trmE), miaA, miaB, miaE, truA(hisT), truB) of either Escherichia coli or Salmonella enterica serovar Typhimurium and the trm5 mutant of Saccharomyces cerevisiae, we have analyzed the influence by the modified nucleosides Q34, mnm(5)s(2)U34, ms(2)io(6)A37, Psi39, Psi55, m(1)G37, and yW37 on -1 frameshifts errors at various heptameric sequences, at which (...) at least one codon is decoded by tRNAs having these modified nucleosides. The frequency of -1 frameshifting was the same in congenic strains only differing in the allelic state of the various tRNA modification genes. In fact, in one case (deficiency of mnm(5)s(2)U34), we observed a reduced ability of the undermodified tRNA to make a -1 frameshift error. These results are in sharp contrast to earlier observations that tRNA modification prevents +1 frameshifting suggesting that the mechanisms by which -1

2003 RNA

100190. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. Full Text available with Trip Pro

of a guanine, 6 bp upstream from the initiation site of transcription, in significant association with the disorder. Tests of promoter activity and DNA binding studies with nuclear proteins suggest that this nucleotide substitution affects the basal transcription rate of the gene. These observations provide some biological insight about the possible mechanism of a genetic predisposition to essential hypertension; they may also have important evolutionary implications. (...) A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. In earlier studies, we provided statistical evidence that individual differences in the angiotensinogen gene, the precursor of the vasoactive hormone angiotensin II, constitute inherited predispositions to essential hypertension in humans. We have now identified a common variant in the proximal promoter, the presence of an adenine, instead

1997 Journal of Clinical Investigation

100191. Changes in Phosphoinositide Metabolism with Days in Culture Affect Signal Transduction Pathways in Galdieria sulphuraria Full Text available with Trip Pro

Changes in Phosphoinositide Metabolism with Days in Culture Affect Signal Transduction Pathways in Galdieria sulphuraria The metabolism of phosphatidylinositol-4,5-bisphosphate (PIP2) changed during the culture period of the thermoacidophilic red alga Galdieria sulphuraria. Seven days after inoculation, the amount of PIP2 in the cells was 910 +/- 100 pmol g-1 fresh weight; by 12 d, PIP2 levels increased to 1200 +/- 150 pmol g-1 fresh weight. In vitro assays indicated that phosphatidylinositol (...) monophosphate (PIP) kinase specific activity increased from 75 to 230 pmol min-1 mg-1 protein between d 7 and 12. When G. sulphuraria cells were osmostimulated, transient increases of up to 4-fold could be observed in inositol-1,4,5-trisphosphate (IP3) levels within 90 s, regardless of the age of the cells. In d-12 cells, the increase in IP3 was preceded by a transient increase of up to 5-fold in specific PIP kinase activity, whereas no such increase was detected after osmostimulation of d-7 cells

1999 Plant physiology

100192. Transient interaction of BBP/ScSF1 and Mud2 with the splicing machinery affects the kinetics of spliceosome assembly. Full Text available with Trip Pro

Transient interaction of BBP/ScSF1 and Mud2 with the splicing machinery affects the kinetics of spliceosome assembly. Removal of introns from pre-mRNA is an essential step of gene expression. The splicing reaction is catalyzed in a large complex termed the spliceosome. Introns are recognized during the early steps of spliceosome assembly with the formation of commitment complexes. Intron recognition is mediated by the interaction of splicing factors with conserved sequences present in the pre (...) ), but is not detectable in commitment complex 1 (CC1). Furthermore, genetic and biochemical depletion of BBP demonstrated that it is required for CC2 formation. In addition we observed that BBP and Mud2 are not detectable in pre-spliceosomes. These are the first commitment complex components that are shown to be released during or immediately after pre-spliceosome formation. Interestingly, depletion of BBP or disruption of MUD2 had no significant effect on pre-spliceosome formation and splicing in vitro but led

1999 RNA

100193. Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent Full Text available with Trip Pro

Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent Genetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn's disease in affected parents and offspring.To compare affected parent-child pairs with Crohn's disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect.137 (...) affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied. Age at onset of symptoms and diagnosis were ascertained by interview and disease confirmed from clinical records.Of the 137 affected parent-child pairs, 50 had Crohn's disease only, 51 had ulcerative colitis only, and in 36, one had Crohn's disease and the other ulcerative colitis. The median age of parents at diagnosis was 17.5 years older, 16 years older, and 18 years older in the Crohn's disease, ulcerative

1999 Gut

100194. Laparoscopic resection does not adversely affect early survival curves in patients undergoing surgery for colorectal adenocarcinoma. Full Text available with Trip Pro

Laparoscopic resection does not adversely affect early survival curves in patients undergoing surgery for colorectal adenocarcinoma. To determine the survival curves for laparoscopic resection (LR) of colorectal cancer.Laparoscopic resection for cure of colorectal cancer is controversial, and survival curves have not been determined.A prospective database of 177 consecutive LRs of colorectal cancers performed between November 1991 and 1997 was reviewed. The TNM classification (stage 0, I, II (...) -up was 24 months for patients with stage I, II, and III disease and 9 months for patients with stage IV disease. Observed 2-year survival rates were 100% stage I, 88.7% stage II, 80.6% stage III, and 28.6% stage IV. Survival rates at 4 years were 100% stage I, 79.5% stage II, 53.7% stage III, and 0% stage IV. No trocar site recurrence was observed.Early survival curves for patients with colorectal cancer who underwent LR do not differ negatively from historical controls for conventional surgery

1999 Annals of Surgery

100195. c-Myc Regulates Cyclin D-Cdk4 and -Cdk6 Activity but Affects Cell Cycle Progression at Multiple Independent Points Full Text available with Trip Pro

cycle. To gain a clearer understanding of the role of c-Myc in cellular proliferation, we have performed a comprehensive analysis of the components that regulate cell cycle progression. The largest defect observed in c-myc-/- cells is a 12-fold reduction in the activity of cyclin D1-Cdk4 and -Cdk6 complexes during the G0-to-S transition. Downstream events, such as activation of cyclin E-Cdk2 and cyclin A-Cdk2 complexes, are delayed and reduced in magnitude. However, it is clear that c-Myc affects (...) c-Myc Regulates Cyclin D-Cdk4 and -Cdk6 Activity but Affects Cell Cycle Progression at Multiple Independent Points c-myc is a cellular proto-oncogene associated with a variety of human cancers and is strongly implicated in the control of cellular proliferation, programmed cell death, and differentiation. We have previously reported the first isolation of a c-myc-null cell line. Loss of c-Myc causes a profound growth defect manifested by the lengthening of both the G1 and G2 phases of the cell

1999 Molecular and cellular biology

100196. Increased risk of gastric cancer in males affects the intestinal type of cancer and is independent of age, location of the tumour and atrophic gastritis. Full Text available with Trip Pro

Increased risk of gastric cancer in males affects the intestinal type of cancer and is independent of age, location of the tumour and atrophic gastritis. Male sex, high age and atrophic gastritis (AG) are risk conditions for gastric carcinoma (GCA). We have studied the magnitude of the sex-bound risk of GCA and whether this risk is an independent risk factor for GCA or whether it is related to the risks that are mediated by age and AG. The observed frequencies of males and females in different (...) of the female sex in IGCA were independent of age of the patient and location of the tumour in the stomach. These phenomena were also independent of AG: the overrepresentation of males and the underrepresentation of females were observed in IGCA patients with normal, non-atrophic mucosa as well as in IGCA patients with AG. We conclude that the sex is an independent risk factor for IGCA, and that the phenomena which lead to overrepresentation of males and underrepresentation of females among IGCA patients

1988 British journal of cancer

100197. Factors affecting uniformity in interpretation of planar thallium-201 imaging in a multicenter trial. The Multicenter Study on Silent Myocardial Ischemia (MSSMI) Thallium-201 Investigators. (Abstract)

Factors affecting uniformity in interpretation of planar thallium-201 imaging in a multicenter trial. The Multicenter Study on Silent Myocardial Ischemia (MSSMI) Thallium-201 Investigators. This study was designed to assess factors affecting interobserver agreement in interpretation of planar thallium-201 stress imaging in the Multicenter Study on Silent Myocardial Ischemia (MSSMI).Five hundred fifty-six planar thallium-201 images were interpreted in 24 clinical centers and in a Radionuclide (...) Core Laboratory. The trial's Coordinating and Data Center observed that the participating clinical centers interpreted a significantly greater number of thallium-201 stress studies as abnormal (i.e., myocardial ischemia or scar) than the Core Laboratory, and overall agreement was poor (kappa 0.27).Agreement in image interpretation between clinical centers and the Radionuclide Core Laboratory was analyzed by kappa statistics. The reproducibility of the Core Laboratory results on 41 randomly selected

1993 Journal of the American College of Cardiology

100198. Subarachnoid local anesthetic block does not affect morphine absorption from paired intramuscular and subcutaneous injection sites in the elderly patient. (Abstract)

Subarachnoid local anesthetic block does not affect morphine absorption from paired intramuscular and subcutaneous injection sites in the elderly patient. Morphine absorption from subcutaneous and intramuscular injection sites is dependent on local skin and muscle blood flow. Normally, drug absorption from intramuscular and subcutaneous injections at the same anatomical site is comparable, but spinal anesthesia alters muscle and skin blood flow in the blocked area. This study measured morphine (...) absorption from pairs of intramuscular and subcutaneous injection sites at vastus lateralis and deltoid following a single dose of morphine sulfate in the presence of spinal anesthesia. Differences between the maximum concentration achieved after injection (Cmax) and the time at which this occurred (Tmax) were not significant when absorption for each "same-site" pair of injections was compared, but Tmax after intramuscular injection at vastus lateralis was significantly longer than that observed

1993 Anesthesia and analgesia Controlled trial quality: uncertain

100199. The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders. (Abstract)

The comparative efficacy of carbamazepine low and high serum level and lithium carbonate in the prophylaxis of affective disorders. The prophylactic efficacy of carbamazepine slow release (CBZ) at ke different blood levels and lithium carbonate slow release (LI) was compared in a retrospective/prospective, randomized, 2-year open trial. 84 patients with a DSM-III-R diagnosis of recurrent affective disorder who had no prophylactic medication in the 2 years preceding the trial (no LI (...) nonresponders), were randomly allocated to three treatment groups: CBZ low (15-25 mumol/l), CBZ high (28-40 mumol/l) and LI (0.6-0.8 mumol/l). Fifty-eight patients completed the full observation period of 2 years, 26 patients dropped out. There were no statistically significant differences in the efficacy of the prophylactic treatment for bipolar patients. For the unipolar patients, the group with a low CBZ serum level showed no reduction in the duration of episodes. The two other treatment groups seem

1993 Journal of Affective Disorders Controlled trial quality: uncertain

100200. Lovastatin does not affect oral glucose tolerance in hypercholesterolemic patients. (Abstract)

Lovastatin does not affect oral glucose tolerance in hypercholesterolemic patients. In 15 non-diabetic Type II hypercholesterolemic patients, the effect of 80 mg lovastatin daily on oral glucose tolerance was investigated. Using a randomized, double-blind, two-panel, parallel design, patients on a low cholesterol diet received lovastatin (n = 7) or placebo (n = 8) for 6 weeks. After 6 weeks of treatment, patients receiving lovastatin had a significant reduction in total cholesterol (30%), LDL (...) -cholesterol (36%), and triglycerides (26%). Time courses of plasma glucose and serum insulin changes from baseline after the oral glucose tolerance test were evaluated by AUC. No statistically significant differences were observed in the AUC of changes from baseline between treatment groups or within either treatment group at prestudy, 6 weeks, and poststudy. No patient had a clinically important laboratory or clinical drug-related adverse effect during the study. This study demonstrated that short-term

1993 Journal of clinical pharmacology Controlled trial quality: uncertain

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