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Biomedical subjects

R Moore

Publications and source records attributed to R Moore.

At least 55 records · Page 3Linked to original sources
PubMed1995

Maternal plasma human immunodeficiency virus type 1 RNA level: a determinant and projected threshold for mother-to-child transmission.

To prevent mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission, it is important to identify its determinants. Because HIV-1 RNA levels can be reduced by antiviral therapy, we examined the role of maternal plasma HIV-1 RNA level in mother-to-child transmission. We used quantitative competitive PCR to measure HIV-RNA in 30 infected pregnant women and then followed their infants prospectively; 27% of the women transmitted HIV-1 to their infants and maternal plasma HIV-1 RNA level correlated strikingly with transmission. Eight of the 10 women with the highest HIV-1 RNA levels at delivery (190,400-1,664,100 copies per ml of plasma) transmitted, while none of the 20 women with lower levels (500-155,800 copies per ml) did (P = 0.0002). Statistical analysis of the distribution of HIV-1 RNA loads in these 30 women projected a threshold for mother-to-child transmission in a larger population; the probability of a woman with a viral RNA level of < or = 100,000 copies per ml not transmitting is predicted to be 97%. Examination of serial HIV-1 RNA levels during pregnancy showed that viral load was stable in women who did not initiate or change antiviral therapy. These data identify maternal plasma HIV-1-RNA level as a major determinant of mother-to-child transmission and suggest that quantitation of HIV-1 RNA may predict the risk of transmission.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Prolonged action of a chimeric interleukin-2 receptor (CD25) monoclonal antibody used in cadaveric renal transplantation.

A high affinity chimeric CD25 mAb (chRFT5: SDZ CHI 621) blocking interleukin-2 binding to the interleukin-2 receptor alpha-chain was evaluated in a phase I/II study in human renal cadaveric transplantation. The chRFT5 was well tolerated with no immediate adverse effects during 6 spaced infusions (from before transplantation to day 24) in 24 patients escalating from 2.5- to 25-mg dosages. The chRFT5 had a long terminal half-life with a mean of 13.1 days. There was good correlation between the detection of chRFT5 in the serum by radioimmunoassay, the coating and suppression of CD25 on T cells, and antibody activity in patient serum samples. The chRFT5 activity persisted in vivo for up to 120 days. No antibody response to the chRFT5 was detected in any of the patients, even though two patients who required treatment with antithymocyte globulin or OKT3 developed xenogeneic antiglobulin responses while chRFT5 was still present in vivo. There was a 33% incidence of rejection and the first rejection episode always occurred during chRFT5 therapy. Patients who did not reject during therapy did not reject during the first year following transplantation. Equal numbers of patients received dual and triple immunosuppressive therapy together with chRFT5. Posttransplant lymphoproliferative disorder developed in 2 patients, both on triple therapy, at 9 months after transplantation. The disorder did not develop in any patient receiving dual therapy, and no further cases have been observed to a minimum of 2 years' follow-up. No other viral, fungal, or bacterial infectious complications were prevalent in patients treated with chRFT5.

Adult↗
PubMed1995

Toward vital status sweeps: a case history in sequential monitoring.

We use data from the Cardiac Arrhythmia Suppression Trial (CAST) to demonstrate the sensitivity of sequential monitoring to the timeliness of survival data. In CAST vital status sweeps were not routinely performed prior to the times of sequential analysis. Examination of the delay between death and reporting of death shows that the change in the time of sequential analysis by even as few as several months can have dramatic impact on the results of the sequential analysis.

Anti-Arrhythmia Agents↗
PubMed1995

Molecular engineering of microsomal P450 2a-4 to a stable, water-soluble enzyme.

Peptitergented P450 2a-4 (Pepti-P450), a water-soluble form of the mouse microsomal P450 2a-4, was genetically engineered and expressed in Escherichia coli. The NH2-terminal hydrophobic sequence (positions 2 to 19) of Pepti-P450 was replaced by a peptitergent PD1, amphipathic peptide consisting of 24 residues (C. E. Schafmeister, L. J. Miercke, and R. M. Stroud (1993) Science 262, 734-738). The expression level of Pepti-P450 (90,000 molecules/cell) was at least four times greater than that of wild-type P450 2a-4. Since Pepti-P450 was quite stable and was expressed as a peripheral membrane protein, it can be easily purified from the membrane fraction treated with Na2CO3 without using any detergents during the chromatographic steps. The purified Pepti-P450 retained the spectral and catalytic properties of the unmodified enzyme with a similar Km value for steroid 15 alpha-hydroxylase activity (19.7 microM in comparison to 14.2 microM of the wild-type). Gel permeation chromatography showed that the purified Pepti-P450 in the detergent-free buffer was an oligomer with an approximate molecular mass of 450 kDa. The replacement of the hydrophobic anchor domain with an amphipathic helix such as peptitergent, therefore, may provide a general method for engineering membrane-bound P450s to soluble enzymes.

Amino Acid Sequence↗
PubMed1995

[Fear of dental treatment. Prevalence and characteristics among adult Danes].

A random sample of residents of the municipality of Aarhus were telephone interviewed about fear of dental treatment and characteristics of any pre-existing dental anxiety. Results showed that 4.2% of 539 residents surveyed had extreme anxiety and 6% were moderately afraid. Results of dental anxiety, especially in the odontophobic group, were years of avoidance of treatment and associated poor subjective perceptions of oral health. Logistic analyses revealed that although dental drilling was the identifying feature of dental anxiety characteristics, the drill could be symbolic for the many persons who perceived dentists as treating them with putdowns, angry comments and hardhandedness. Other persons suffered from multiple fears, which may have an accumulative effect on dental treatment anxiety. A conceptual model is presented as derived from present results and existing clinical and epidemiologic literature.

Adolescent↗
PubMed1995

Sexually dimorphic DNA demethylation in the promoter of the Slp (sex-limited protein) gene in mouse liver.

Mouse Slp, a duplicate of the fourth complement component (C4) gene, exhibits EDTA-independent complement activity with a hepatic expression that is male specific. To provide an underlying mechanism for the male-specific expression, we have analyzed the promoter activity of the various 5'-flanking sequences and CpG demethylation of the Slp gene. Transient transfections using HepG2 cells indicate that the element TTCCGGGC (nt -124 to -117) regulates the promoter activity. Moreover, CpG at position -121 of this regulatory element is demethylated to a much higher degree in males than in females. This sexually dimorphic DNA demethylation is consistent with the male-specific expression of the Slp gene in DBA/2 males. The regulatory element binds to the different TTCCGGGC-specific nuclear proteins depending on the methylation of the CpG site. In contrast, the corresponding CpG at position -119 of the C4 gene, which is expressed in both males and females, is demethylated at equal and high levels in both sexes. We therefore propose that the DNA demethylation and methylation-sensitive transcription factors may be a part of the regulatory mechanism for the male-specific expression of the Slp gene.

Animals↗
PubMed1995

Public knowledge, attitudes, and beliefs about homeless people: evidence for compassion fatigue.

Media reports suggest that the public is becoming impatient with the homeless--that so-called "compassion fatigue" has gripped the nation. This characterization of public sentiment could have important policy consequences-- restrictive measures can be justified by growing public impatience, and progressive housing policies seem feasible within a hostile climate of opinion. But evidence to support the compassion fatigue notion is anecdotal. We examine the issue by tracking the results of public opinion polls and by reporting detailed evidence from a nationwide random-digit dial telephone survey (N = 1,507) concerning knowledge attitudes and beliefs about homeless people. To be sure, the public sees homelessness as an undesirable social problem and wants something done about it. However, although the homeless are clearly stigmatized, there is little evidence to suggest that the public has lost compassion and is unwilling to support policies to help homeless people.

Adolescent↗
PubMed1995

The looming of spiders: the fearful perceptual distortion of movement and menace.

The current study examined the relation between the perception that fear-stimuli are looming and fearful cognitive distortions. As hypothesized, high-fear-of-spider Ss were significantly more likely than low-fear Ss to imagine that a spider in a room would move rapidly and selectively to them in proximity, rather than towards three other individuals in the same physical space. This finding was observed with a measure of perceptual-cognitive distortion as well as with self-reports. High-fear Ss were also more likely to perceive spiders as angry and belligerent, as intending to move towards them, and as singling them out from other people. These results suggest that perceptions of looming danger and fearful cognitive distortions are closely linked phenomena. Finally, the perception that spiders are looming and the other cognitive variables could be used to successfully classify the fear-group memberships of the Ss in 98% of the cases. Perceptions that spiders are looming made the single largest unique contribution to the discriminant classification function.

Adult↗
PubMed1995

Temporal changes in permeability and structure of piglet ileum after site-specific infection by Cryptosporidium parvum.

BACKGROUND/AIMS: Cryptosporidiosis is an important enteric infection associated with diarrhea in humans. The structural and functional basis for diarrhea is poorly understood. The aim of the study was to determine the structural and functional basis of diarrhea in cryptosporidiosis during evolving host cell-parasite interactions in the intestine. METHODS: We used the piglet model for temporal studies of alterations in intestinal epithelial structure and function that occurred 12-48 hours postinoculation. Segments of intestine were directly inoculated in vivo, harvested, and studied in vitro using Ussing chamber techniques. RESULTS: Villus architectural alterations corresponded to the extent of infection. Increased numbers of lamina propria inflammatory cells were evident at 36 hours postinoculation. Solute and macromolecular permeability was not increased. Glucose-responsive short-circuit current was diminished at 48 hours postinoculation. The short-circuit current response to theophylline was the same in control and infected tissues. CONCLUSIONS: We conclude that passive solute and macromolecular permeability in infected tissues is not significantly increased during parasite-host cell interactions 12-48 hours postinoculation. Electrogenic glucose stimulated Na+ absorption, a function principally of villus absorptive cells, is impaired, and electrogenic Cl- secretion, a function of crypt epithelial cells, remains the same. These findings parallel structural observations that include loss of the Na+/glucose-transporting villus epithelium without loss of crypt epithelium.

Animals↗
PubMed1995

Erythrocyte membrane fatty acid composition as a marker of dietary compliance in hyperlipidaemic subjects.

Dietary intervention is the first treatment step in management of hyperlipidaemia, but there are few objective criteria of compliance. Whether intensive dietary intervention would produce a detectable change in erythrocyte membrane fatty acid composition which could be used as a marker of compliance was examined in 31 new hyperlipidaemic patients. Over a 6 month period, body mass index fell from 29.0 to 26.9 kg/m2 (P < 0.001) and total cholesterol by 19% from 8.16 to 6.58 mmol/l (P < 0.001). The energy derived from fat was reduced from 38.5% to 29.6% (P < 0.001), and the ratio of dietary polyunsaturated to saturated (P:S) fatty acids in the diet increased from 0.45 to 0.66 (P < 0.01). Small but significant changes were recorded in several red cell membrane fatty acids, and the P:S ratio increased from 0.91 to 1.13 (P < 0.001). It would appear, therefore, that red cell membrane changes parallel dietary changes and hence are a potential marker for compliance with dietary changes.

Adult↗
PubMed1995

Lifetime and five-year prevalence of homelessness in the United States: new evidence on an old debate.

A 1990 household-based telephone survey of 1,507 people was followed up by surveying a subsample of those interviewed for the initial report. Results showed very high prevalence figures for homelessness, quite close to those found in the earlier survey. Moreover, using explicit and stringent definitions of literal homelessness and doubling up, most periods of homelessness were found to last for more than one month and, particularly with regard to literal homelessness, to involve serious deprivations and violent victimization.

Adult↗
PubMed1995

Changes in endogenous cytokines, adhesion molecules and platelets during cytokine-induced tumour necrosis.

The aim of this study was to investigate mechanisms of anti-tumour activity and necrosis induced by combinations of tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). In a breast cancer xenograft model, locally injected recombinant human TNF-alpha arrested growth of established tumours in the absence of overt necrosis. Macroscopic necrosis occurred when rat IFN-gamma, which had no anti-tumour activity as a single agent, was given systemically. Treatment with TNF-alpha and IFN-gamma caused focal engorgement of tumour capillaries with erythrocytes, intravascular recruitment of polymorphonuclear cells and platelet adherence to the tumour vascular endothelium 4 h after the combined treatment. This was followed by destruction of tumour vascular endothelium and both necrosis and apoptosis of tumour cells. Concomitant with these changes, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the increase of stromal (murine) mRNA levels for TNF-alpha, TNF receptor 55 kDa, TNF receptor 75 kDa, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, P-selectin and interleukin 6 (IL-6). Thus, the effect of the combined TNF-alpha and IFN-gamma therapy involved the selective destruction of the tumour vasculature, death of tumour cells and increased expression of a series of stromal cytokines, cytokine receptors and adhesion molecules, which could be implicated in the observed events.

Adenocarcinoma, Mucinous↗
PubMed1995

Differential diagnosis of odontophobic patients using the DSM-IV.

Categories of extreme anxiety for dental treatment were derived using DSM-IV psychiatric criteria. A sample of 40 men and 40 women patients with extreme dental anxiety were initially evaluated with Dental Anxiety Scale (DAS), Trait Anxiety Inventory (STAI-T) and Geer Fear Scale (GFS). Patients all had DAS scores > or = 15 indicating extreme dental anxiety and were further evaluated with clinical interviews, Dental Fear Survey (DFS), Dental Beliefs Survey (DBS) and Mood Adjective Checklist (MACL). Results showed that 46% of 80 patients complained mainly of powerlessness and embarrassment about dental treatment while also having greater DBS scores than other categories, i.e. social phobia. Another 19% reported conditioned specific phobias (pain, drilling, injection, etc.) most often and lower DBS and GFS scores than other groups; while 35% had broader general anxiety complications, such as multiple phobias and agoraphobia with or without general anxiety symptoms (higher GFS and STAI-T compared to others). Symptoms of general anxiety disorder (GAD) were present in 30 of 80 patients, who had greater STAI-T and GFS and lower MACL scores than non-GAD patients. These results have implications for appropriate treatment strategies.

Adult↗
PubMed1995

A DNA methylation site in the male-specific P450 (Cyp 2d-9) promoter and binding of the heteromeric transcription factor GABP.

The Cyp 2d-9 gene encodes the male-specific steroid 16 alpha-hydroxylase in mouse liver and shares a conserved regulatory element (-100TTCCGGGC-93) with another male-specific Slp promoter. As shown with the Slp promoter (N. Yokomori, R. Moore, and M. Negishi, Proc. Natl. Acad. Sci. USA 92:1302-1306, 1995), the male-preferential demethylation also occurs at CpG/-97 in the Cyp 2d-9 promoter. The transcription factor which specifically binds to the demethylated element has been purified. The peptide sequences reveal that the factor consists of GABP alpha and GABP beta 1 with Ets and Notch motifs, respectively. Both DNase I footprinting and gel shift assays indicate that the bacterially expressed glutathione S-transferase-GABP fusion proteins bind to the regulatory element only when CpG/-97 is demethylated. Moreover, Cyp 2d-9 promoter is trans-activated by coexpression of GABP proteins in HepG2 cells. Given the additional results that CpG/-50 of the female-specific steroid 15 alpha-hydroxylase (Cyp 2a-4) promoter is preferentially demethylated in the females, the sex-specific expressions of the P450 genes correlate very well with DNA demethylation. We also conclude that GABP is a methylation-sensitive transcription factor and is a potential transcription activator of the male-specific Cyp 2d-9 promoter.

Amino Acid Sequence↗
PubMed1995

A nuclear factor (NF2d9) that binds to the male-specific P450 (Cyp 2d-9) gene in mouse liver.

Expression of the Cyp 2d-9 (steroid 16 alpha-hydroxylase) gene in mouse liver is male specific in such Mus musculus domesticus strains as FVB/N, whereas the corresponding P450 genes in the wild mouse species Mus spretus are not sex specific in their expression. These parental differences in the gene expressions were independently inherited in F1 offspring from crosses of FVB/N and M. spretus. A 5' flanking sequence (-110CTC CTCCCTATTCCGGGCC-92) was defined as a regulatory element (named SDI-A1) for the domestic Cyp 2d-9 promoter. The nucleotide which corresponds to T at position -99 within SDI-A1 was found to be substituted with C in the wild mouse P450 genes. The placing of C at position -99 abolished the transcriptional activity of SDI-A1 in HepG2 cells as well as the binding of SDI-A1 to a nuclear factor. This factor (designated NF2d9) was purified from mouse nuclear extracts, and its cDNA cloned. The purified NF2d9 bound to SDI-A1 but not to the mutated SDI-A1 with C at position -99. The deduced amino acid sequence revealed that NF2d9 is 72 and 94% identical to mouse CP2 and human LBP-1a, respectively. NF2d9 thus belongs to the CP2 family and is the mouse homolog of human LBP-1a, which modulates human immunodeficiency virus type 1 transcription. Anti-NF2d9, which was raised against the bacterially expressed protein, supershifted the SDI-A1 complex with the liver nuclear extract. Both the bacterially expressed and in vitro-translated NF2d9 inhibited SDI-A1 complex formation, although they did not bind to SDI-A1 directly. The results, therefore, indicate that the domestic Cyp 2d-9 gene can be regulated through a specific association of NF2d9 with SDI-A1.

Amino Acid Sequence↗