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Biomedical subjects

T Moore

Publications and source records attributed to T Moore.

At least 127 records · Page 7Linked to original sources

Correlation of perinatal transmission of human immunodeficiency virus type 1 with maternal viremia and lymphocyte phenotypes.

OBJECTIVE: To determine whether maternal transmission of human immunodeficiency virus (HIV) is correlated with increased quantities of HIV, decreased frequencies of CD4+ T cells, or increased levels of CD8+ T cells in the transmitting mother. METHODS: Peripheral blood obtained from HIV-infected women at different times during pregnancy was used to measure quantitative cell-associated HIV-1 and CD3+CD4+ and CD3+CD8+ proportions; the plasma was used to perform measurements of quantitative viremia by culture and subsequently to measure quantitative HIV-1 ribonucleic acid levels. These measurements were analyzed with respect to their association with HIV transmission to the baby, which occurred in one fourth of the cases. The children were also studied to determine whether HIV-1 was detected near birth or not until 1 to 8 weeks of life. RESULTS: Increased clonal frequencies of HIV-1-infected peripheral blood mononuclear cells were found in mothers of infected children; fivefold fewer cells were required for a positive culture result (median cell numbers of 10(4.5) vs 10(5.2); p = 0.008). Higher frequencies of infected cells were seen in mothers of babies with evidence of infection at birth than in mothers of infected babies without evidence of infection at birth (p < 0.05). Plasma viremia was measured in 10% of cultures without regard to whether the mothers transmitted virus to their babies. Increased levels of ribonucleic acid as detected by the branched-chain DNA method were measurable more often (45% vs 17%) in the mothers of infected children than in mothers of uninfected children. Proportions of CD4+ and CD8+ T cells were indistinguishable in these two groups of women. CONCLUSIONS: Increased viremia was present in mothers who transmitted HIV to their offspring. This variable could be used to select women at highest risk of transmitting HIV to their offspring for treatment to decrease the HIV burden five-fold.

CD4-CD8 Ratio↗

Effects of antiviral therapy on the production of anti-human immunodeficiency virus-specific immunoglobulin in infants and children.

The effect of zidovudine therapy on human immunodeficiency virus (HIV)-specific antibody production was studied in 64 HIV-1-infected infants and children > 6 months old. HIV-specific in vitro antibody production (IVAP) was measured in cultures of peripheral blood mononuclear cells (PBMC). IVAP decreased in 85% of children after zidovudine was initiated (mean decline, 1 log within 2 months). Effects were seen as early as 1 week after starting zidovudine. No change in IVAP was seen in children not treated. In comparison, plasma core (p24) antigen levels declined and CD4+ lymphocytes increased in only 42% and 52%, respectively, of treated subjects. Thus, the production of antibody to HIV-1 decreases rapidly after the initiation of antiretroviral therapy. This response to therapy may provide a simple and sensitive method of monitoring antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

Sensing of aromatic compounds by the DmpR transcriptional activator of phenol-catabolizing Pseudomonas sp. strain CF600.

The dmp operon of the pVI150 catabolic plasmid of Pseudomonas sp. strain CF600 encodes the enzymes involved in the catabolism of phenol and methylphenols. The regulator of this dmp pathway, DmpR, is a member of the NtrC family of transcriptional activators and controls transcription of the dmp operon in response to aromatic effector compounds (V. Shingler, M. Bartilson, and T. Moore, J. Bacteriol. 175:1596-1604, 1993). Using a lux gene fusion reporter system, in which the DmpR-regulated operon promoter controls the expression of luciferase activity, we have shown in the study reported here that DmpR is activated by, but responds differentially to, the presence of a wide range of aromatic compounds. In many microbial regulatory systems, including some members of the NtrC family, the response to environmental fluctuations involves information transfer from surface sensory proteins to transcriptional regulators. However, DmpR-mediated activation of phenol metabolism in response to aromatic compounds occurs in the absence of a specific sensory protein. We used hybrids between DmpR and XylR, a structurally related regulator of toluene and xylene metabolism, to demonstrate that it is the amino-terminal domains of these regulators that determine the specificity of transcriptional activation. The results suggest that it is the direct interaction of aromatic compounds with the DmpR and XylR proteins that regulates their transcriptional promoting activity.

Amino Acid Sequence↗

FUNCTION OF THE TENSOR MUSCLE IN THE CICADA TIBICEN LINNEI

The calling song and the disturbance squawk of the cicada Tibicen linnei (Insecta: Homoptera) are described in terms of their physical parameters. The calling song is composed of quiet parts, which are very similar to the disturbance squawk, and loud parts, which are amplitude- and rate-modulated. The role of the tensor muscle acting on the tymbal frame in modulating the sound pulse amplitude was investigated. We demonstrate by tensor nerve recordings, by mechanical mimicking of the tensor muscle action and by electrical stimulation of the tensor nerve, that the contraction of the tensor muscle is responsible for (a) initiating sound production and (b) modulating the sound pulse amplitude. These results allow us to construct a model which suggests that the tensor shifts the tymbal into a mechanical working range that enables sound production and modulation of the sound pulse amplitude.

Journal Article↗

AUDITORY THRESHOLD CHANGE IN SINGING CICADAS

The hearing sensitivity in singing cicadas is reduced during sound production by a folding of the tympanal membranes. Using electrophysiological recording and nerve stimulation techniques, we have shown an effect of the folded tympanum on the auditory threshold of two species of cicadas, Tibicen linnei and Okanagana rimosa. Auditory thresholds of both species increased by about 20 dB when the tympana folded during singing. In T. linnei the increase in threshold affected the whole frequency range, from 1 to 16 kHz, in a similar way. Electrical stimulation of one or both auditory nerves resulted in a folding of both tympanal membranes in a way very similar to that seen in singing animals. We have demonstrated that a cicada male is able to adjust its auditory threshold within a range of about 20 dB by the tympanal folding mechanism.

Journal Article↗

Effects of gamma irradiation on the human immunodeficiency virus. A study in frozen human bone-patellar ligament-bone grafts obtained from infected cadavera.

We studied the effects of several different doses of gamma radiation, ranging from 20,000 to 40,000 gray (2.0 to 4.0 megarad), with respect to the inactivation of the human immunodeficiency virus in fresh-frozen, whole bone-patellar ligament-bone grafts. Although the International Atomic Energy Agency has recommended the use of 25,000 gray of gamma radiation for the sterilization of medical products, the dose required for the inactivation of the human immunodeficiency virus in frozen allografts has not been established. Using one of the most sensitive and specific tests for the detection of the human immunodeficiency virus, the polymerase-chain-reaction test, we found that doses of 20,000 or 25,000 gray of gamma radiation did not destroy the genes of the human immunodeficiency virus effectively; DNA of the virus was detectable in the DNA of bone-marrow tissue obtained from grafts treated with these doses. However, DNA of the human immunodeficiency virus was not detectable in the grafts treated with 30,000 or 40,000 gray of gamma radiation. We conclude that a dose of 30,000 gray of gamma radiation or more is necessary for the sterilization of a fresh-frozen bone-patellar ligament-bone allograft, so that it can be used for reconstructive procedures without the risk of transmission of the virus to the recipient.

Bone Transplantation↗

Alteration in the proportion of CD4 T lymphocytes in a subgroup of human immunodeficiency virus-exposed-uninfected children.

OBJECTIVE: The age-related changes in the proportion of CD4 and CD8 lymphocytes in human immunodeficiency virus (HIV)-seronegative children born to HIV-infected mothers (seroreverters) were compared with the changes in these lymphocyte subsets in children born to seronegative women to assess a possible effect of exposure to HIV without infection. DESIGN: There were 146 seroreverter and 72 seronegative children. The median CD4 and CD8 percentages for each of these two groups of children were compared retrospectively at 3-month intervals from birth through 27 months and at a tenth interval for the time beyond 27 months. The weighted average of the within-subject rate of change of CD4 and CD8 percentages were also compared between the two groups. Finally, for each subject, the proportion of the subject's CD4 percentage assays which were <10th percentile of the entire study population (30%) was calculated, and the distributions of the subject-specific proportions were then compared between the seronegative and seroreverter groups using the Wilcoxon rank sum test. The proportion of CD8 assays <10th percentile (12%) or > 90th percentile (26%) were also computed for each subject, and the distributions of the proportions were compared similarly. . RESULTS: The median CD4 percentage of seroreverter children was lower than that for the seronegative children at every interval from birth through 27 months and for the last interval for values obtained at greater than 27 months, although the comparison was statistically significant only at the 4- to 6-month period. The weighted average of the within-subject rate of change of CD4 percentage was -0.09 and -3.0 per year (P = .04), and of CD8 percentage was 1.3 and 1.0 (P = .67), for the seroreverter and seronegative children, respectively. There were significantly more children in the seroreverter group than in the seronegative group who had repeated assays in which the CD4 percentage was < 10th percentile for age (P < .00005). In addition, there was a subset of 10 seroreverter children (6.8%) who had CD4 percentages < 30% on > 50% of their assays, as compared with only one (1.4%) seronegative child. The proportion of CD8 assays < 10th percentile or > 90th percentile were not significantly different between the two groups of children. CONCLUSIONS: The CD4 proportions were persistently lower in the seroreverter than in the seronegative population, although only reaching statistical significance in 1 of 10 3-month intervals. This finding may be due to a subgroup of seroreverter children who have persistently low CD4 lymphocyte percentages.

CD4-CD8 Ratio↗

Understanding variation in rates of referral among general practitioners: are inappropriate referrals important and would guidelines help to reduce rates?

OBJECTIVES: To determine the extent to which variation in rates of referral among general practitioners may be explained by inappropriate referrals and to estimate the effect of implementing referral guidelines. SETTING: Practices within Cambridge Health Authority and Addenbrooke's Hospital, Cambridge. MAIN OUTCOME MEASURES: Data on practice referral rates from hospital computers, inappropriate referrals as judged by hospital consultants, and inappropriate referrals as judged against referral guidelines which had been developed locally between general practitioners and specialists. Effect of referral guidelines on referral patterns as judged by general practitioners using the guidelines in clinical practice. RESULTS: There was 2.5-fold variation in referral rates among general practices. According to the specialists, 9.6% (95% confidence interval 6.4% to 12.9%) of referrals by general practitioners and 8.9% (2.6% to 15.2%) of referrals from other specialists were judged possibly or definitely inappropriate. Against locally determined referral guidelines 15.9% of referrals by general practitioners were judged possibly inappropriate (11.8% to 20.0%). Elimination of all possibly inappropriate referrals could reduce variation in practice referral rates only from 2.5-fold to 2.1-fold. An estimate of the effect of using referral guidelines for 60 common conditions in routine general practice suggested that application of guidelines would have been unlikely to reduce rates of referral in hospital (95% confidence interval -4.5% to 8.6% of consultations resulting in referral). CONCLUSION: The variation in referral rates among general practitioners in Cambridge could not be explained by inappropriate referrals. Application of referral guidelines would be unlikely to reduce the number of patients referred to hospital.

Decision Making↗

Characterization of a cDNA clone encoding a chloroplast-targeted Clp homologue.

Efforts to identify cDNA clones encoding chloroplastic envelope membrane proteins of Pisum sativum L. led to the isolation of a clone encoding a 92 kDa protein found in both the inner envelope membrane and the soluble fraction of chloroplasts. Sequential transcription and translation from the insert of this clone yielded a 102 kDa protein that could be imported into chloroplasts and processed to a 92 kDa form. Although the protein was identified because it reacted with antibodies to chloroplastic envelope proteins, the imported 92 kDa protein was recovered primarily in the soluble fraction of chloroplasts. The deduced amino acid sequence of this protein has strong similarity to the Clp proteins, a recently described family of highly conserved proteins present in all organisms examined to date. The physiological significance of the presence of this protein in chloroplasts is discussed.

Amino Acid Sequence↗

Conditioned defeat in the Syrian golden hamster (Mesocricetus auratus).

When singly housed under laboratory conditions, male Syrian golden hamsters routinely attack novel conspecific intruders introduced into their home cages. As we report here, after being repeatedly defeated by a larger, more aggressive intruder, such normal territorial aggression on the part of the resident hamsters is replaced by defensive behavior and flight. We have found that such conditioned defeat (CD) can be reliably induced by a series of 5-min trials with an aggressive intruder whether these trials are spread over 4 days or are all given on the same day. A useful behavioral criterion for the appearance of CD during acquisition is the first occurrence of anticipatory flight (AF), i.e., the first time the resident flees from the next aggressive intruder before being attacked. CD shows generalization: Animals trained to the AF criterion (AF Group) subsequently show defensive behavior toward, and even flee from, intruders which show absolutely no sign of aggressiveness. Animals in the AF Group persisted in such defense behavior for two test sessions; animals given three additional defeat trials beyond the appearance of AF (AF + 3 Group) showed a greater magnitude and persistence of defense and flight. A comparison of CD-trained animals which met a non-aggressive intruder (NAI) every day for 5 days to similarly trained animals which met the intruder only on the fifth day after acquisition suggests that CD diminishes passively as a function of time and not as the consequence of repeated encounters with a nonaggressive stimulus animal. We also found that near ideal NAIs could be prepared by treating nonaggressive hamsters with high doses of diazepam: animals so treated locomote more or less continuously around the cage virtually ignoring the subject. An unexpected observation was that subjects in the AF Group tended to closely follow these diazepam-treated, rapidly locomoting NAIs around the cage. Following may be an example of the "risk assessment" activities directed toward a potential threat. The development of a rapid and reliable technique for inducing CD in hamsters sets the stage for further physiological and pharmacological work on this interesting phenomenon.

Aggression↗

Cloning and nucleotide sequence of the gene encoding the positive regulator (DmpR) of the phenol catabolic pathway encoded by pVI150 and identification of DmpR as a member of the NtrC family of transcriptional activators.

The catabolic plasmid pVI150 of Pseudomonas sp. strain CF600 encodes all the genetic information required for the regulated metabolism of phenol and some of its methyl-substituted derivatives. The structural dmp genes of the pathway are clustered in a single operon that lies just downstream of a -24 TGGC, -12 TTGC nif/ntr-like promoter sequence. Promoters of this class are recognized by a minor form of RNA polymerase utilizing sigma 54 (NtrA, RpoN). Primer extension analysis demonstrated that the dmp operon transcript initiates downstream of the -24, -12 promoter. Transposon insertion mutants, specifically defective in the regulation of the dmp operon, were isolated, and complementation of a phenol-utilization regulatory mutant was used to identify the regulatory locus, dmpR. The 67-kDa dmpR gene product alone was shown to be sufficient for activation of transcription from the dmp operon promoter. Nucleotide sequence determination revealed that DmpR belongs to the NtrC family of transcriptional activators that regulate transcription from -24, -12 promoters. The deduced amino acid sequence of DmpR has high homology (40 to 67% identity) with the central and carboxy-terminal regions of these activators, which are believed to be involved in the interaction with the sigma 54 RNA polymerase and in DNA binding, respectively. The amino-terminal region of DmpR was found to share 64% identity with the amino-terminal region of XylR, which is also a member of this family of activators. This region has been implicated in effector recognition of aromatic compounds that is required for the regulatory activity of XylR.

Amino Acid Sequence↗

Hypertonic saline resuscitation detrimentally affects renal function and survival in dehydrated rats.

The purpose of our studies was to determine whether hypertonic (7.5%) saline (HTS) resuscitation is effective in the setting of dehydration. We compared the effects of HTS (5 cc/kg) to those of Ringer's lactate (RL; 45 cc/kg) on renal function, following resuscitation from hypovolemia in hydrated (free access to food/water) vs. dehydrated (food/water restricted) rats (300-350 g). Renal failure was produced by hemorrhage (15 cc/kg) plus renal artery occlusion (25 min) followed by fluid resuscitation. Dehydration was confirmed by hemoconcentration and weight loss (8-10%). Renal function was assessed at 24 hr using 14C-inulin clearance (Cin) measurements. In hydrated animals, the Cin of RL-treated rats (625 +/- 54 microliters/min/100 g; n = 12) was no different from the Cin in HTS-treated rats (517 +/- 48 microliters/min/100 g; n = 13). Among dehydrated rats, Cin in HTS-treated rats (n = 6) was significantly lower (P < or = 0.05) than in RL-treated rats (n = 5) (117 +/- 33 microliters/min/100 g vs. 542 +/- 84 microliters/min/100 g, respectively). Cin in dehydrated RL-treated rats was not significantly different from that in hydrated RL-treated rats. Furthermore, in dehydrated animals, nine of nine resuscitated with RL survived, compared to six of 13 resuscitated with HTS. All hydrated animals survived. In summary, renal failure was ameliorated by RL and worsened by HTS resuscitation in dehydrated rats. Furthermore, mortality was increased in dehydrated animals resuscitated with HTS compared to RL.

Animals↗

Differential accumulation of transcripts for four tomato 1-aminocyclopropane-1-carboxylate synthase homologs under various conditions.

Degenerate oligonucleotide primers corresponding to conserved regions flanking the active-site domain of 1-aminocyclopropane-1-carboxylate (ACC) synthase (EC 4.4.1.14) were used for the polymerase chain reaction (PCR) to amplify DNA fragments from mRNA isolated from tomato fruit and tomato suspension cell culture. Antibodies raised against two conserved peptide sequences (TNPSNPLGTT and SLSKDLGLPGFRVG) were used to screen for positive colonies, after the PCR products were cloned into a Bluescript plasmid and expressed in Escherichia coli. Four distinct cDNA fragments encoding ACC synthase homologs were isolated. While pBTAS1 and pBTAS4 were obtained from fruit mRNA, cell culture mRNA yielded three sequences, pBTAS1, pBTAS2, and pBTAS3. Sequencing of these gene fragments revealed that pBTAS1 and pBTAS4 were identical to those full-length sequences previously reported by Van Der Straeten et al. [Van Der Straeten, D., Van Wiemeersch, L., Goodman, H. & Van Montague, M. (1990) Proc. Natl. Acad. Sci. USA 87, 4859-4863] and Olson et al. [Olson, D. C., White, J. A., Edelman, J., Harkin, R. N. & Kende, H. (1991) Proc. Natl. Acad. Sci. USA 88, 5340-5344] from tomato fruit, whereas pBTAS2 and pBTAS3 represent new sequences. Ribonuclease protection assays were used to examine the expression of these transcripts under three different conditions of enhanced ethylene production--namely, during fruit ripening, in response to mechanical wounding in fruit tissue, and auxin stimulation in vegetative tissue. Transcripts of pBTAS1 accumulated massively during ripening and wounding but only slightly in response to auxin treatment. Although pBTAS4 was associated with fruit ripening, it was unresponsive to auxin treatment in vegetative tissue. In contrast, the expression of pBTAS2 and pBTAS3 was greatly promoted in auxin-treated vegetative tissue but was absent from fruit tissue. While the expression of pBTAS2 was moderately dependent on wounding, pBTAS3 was unresponsive to wounding. These data support the view that ACC synthase is encoded by a multigene family and that the members are differentially expressed in response to developmental, environmental, and hormonal factors.

Amino Acid Sequence↗