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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
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1992

Management of catastrophic neonatal midgut volvulus with a silo and second-look laparotomy.

The case of a neonate with midgut volvulus and severe intestinal ischemia extending from the ligament of Treitz to the midtransverse colon is presented. Management consisted of abdominal silo application at the initial exploration to obviate the adverse physiological consequences of increased intraabdominal pressure from reperfusion edema of the intestine. The majority of the intestine was salvaged, and a short segment of ileum was resected. This method of treatment resulted in optimal ventilatory status, renal function, and cardiac performance. The advantages of temporary prosthetic wound coverage in selected cases of midgut volvulus include greater physiologic stability through the avoidance of "intraabdominal hypertension" and the ability to monitor the status of the intestine at the bedside.

Duodenal Obstruction↗
PubMed1992

Evolution of phenotypic memory T cells in HIV-1 infected infants and children.

Infants are reported to be devoid of memory T cells at birth but acquired them with time. A cross-sectional study of peripheral blood mononuclear cells from HIV-infected and uninfected infants and children that bear the CD4R0 antigen was undertaken to describe the development of memory T cells. Linear regression lines derived from the data revealed increasing percentages of memory CD4 and CD8 cells in the uninfected children. Memory CD4 cells in the infected children were detected at a frequency equal to or greater than that seen in uninfected children until 6 months of age but subsequently declined with age. In contrast, memory CD8 cells were found to be significantly increased in HIV-infected children early in life with a rate of increase similar to that seen in the uninfected population. This increase in memory CD8 cells may facilitate the early diagnosis of HIV infection.

CD4-Positive T-Lymphocytes↗
PubMed1992

Cell-mediated and humoral immune responses in children infected with human immunodeficiency virus during the first four years of life.

OBJECTIVES: To determine whether cell-mediated and humoral immune responses to recall antigens develop in children infected with the human immunodeficiency virus (HIV) and, if so, whether these responses are retained. METHODS: Children infected with HIV and uninfected children born to mothers infected with HIV were compared with respect to lymphoproliferative responses to recall antigens and protective levels of antibody to bacterial toxoids during the first 4 years of life. RESULTS: Children infected with HIV who were enrolled in a prospective study of the natural history of the infection were relatively normal (1) in their lymphoproliferative responses to diphtheria toxoid, tetanus toxoid, and Candida, and (2) in their ability to make protective diphtheria and tetanus antitoxins during the first 2 years of life. During the next 2 years, attrition was noted in both lymphoproliferative and humoral responses. Attrition in response was not necessarily correlated with declining numbers of helper T cells. CONCLUSIONS: These results suggest that both cellular and humoral immune responses develop early in life in most children infected with HIV, while they remain relatively well both clinically and immunologically. Previously reported severe immune deficits in these children were probably attributable to advanced clinical disease when they were first studied.

Age Factors↗
PubMed1992

Lack of predictive value of maternal human immunodeficiency virus p24 antigen for transmission of infection to their children.

The association of maternal-to-infant transmission of human immunodeficiency virus type 1 (HIV-1) with maternal p24 antigenemia was assessed in 86 HIV-1-infected mothers. We retrospectively examined serum or plasma samples collected in the peripartum period (delivery +/- 11 days; sd 16.89 days; range, delivery +/- 2 months). Immune complexes of p24 antigen and anti-p24 antibody were dissociated using acid hydrolysis (Method A, glycine-HCl buffer; Method B, HCl) in an attempt to increase the sensitivity of the test. The detection of HIV-1 p24 antigenemia in serum was increased from 23 of 86 (26.7%) to 37 of 82 (45.1%) following acid hydrolysis with Method A (chi square = 5.4, P = 0.02) and to 36 of 78 (46.1%) with Method B (chi square = 5.874, P = 0.015). Mothers of HIV-1-infected children were no more likely to have p24 antigenemia than mothers of seroreverted infants when untreated samples were assayed (7 of 23 vs. 10 of 48; chi square = 0.348, P = 0.55). Although acid hydrolysis increased the ability to detect p24 antigen, it did not enhance any association between p24 antigenemia and maternal-to-infant transmission of HIV infection: Method A, 9 of 23 in mothers of infected children vs. 21 of 45 in mothers of seroreverted children (chi square = 0.112, P = 0.738); and Method B, 9 of 22 in mothers of infected children vs. 18 of 42 in mothers of seroreverted children (chi square = 0.014; P = 0.907), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Limb salvage surgery for bone and soft tissue sarcoma. A phase II pathologic study of preoperative intraarterial cisplatin.

Preoperative therapy has been tested as part of limb salvage therapy for localized bone and soft tissue sarcoma of the extremities. The activity of cisplatin (CDDP) by intraarterial (IA) infusion was evaluated in 40 cases of which 36 were evaluable for response. All patients had high-grade sarcomas. All but 3 patients received 3 or 4 courses (24 patients received 4 courses) of CDDP at a dosage of 120 to 150 mg/m2 given over 6 hours every 2 weeks by IA infusion. Patients younger than 18 years of age received the higher dose of CDDP. Treatment was well tolerated with combination antiemetics. One patient experienced severe hearing loss with the first cycle of the higher CDDP dose. Pathologic evaluation of resected osteosarcoma showed a favorable response (90% or greater necrosis) in 8 of 20 evaluable cases and in 3 of 4 patients with malignant fibrous histiocytoma (MFH) of bone (without osteoid). In soft tissue sarcomas, minimal (50% to 89%) necrosis was seen in two of nine cases and none had 90% or greater necrosis. Patients received postoperative chemotherapy based on pathologic response, but the value of this postoperative adjuvant therapy requires further follow-up and is uncertain in this small study. IA CDDP can often cause significant tumor necrosis in patients with bone sarcomas, whereas soft tissue sarcomas are less sensitive to this therapy.

Adolescent↗
PubMed1991

myo-inositol pentakisphosphates. Structure, biological occurrence and phosphorylation to myo-inositol hexakisphosphate.

1. Standard and high-performance anion-exchange-chromatographic techniques have been used to purify myo-[3H]inositol pentakisphosphates from various myo-[3H]inositol-prelabelled cells. Slime mould (Dictyostelium discoideum) contained 8 microM-myo-[3H]inositol 1,3,4,5,6-pentakisphosphate, 16 microM-myo-[3H]inositol 1,2,3,4,6-pentakisphosphate and 36 microM-D-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate [calculated intracellular concentrations; Stephens & Irvine (1990) Nature (London) 346, 580-583]; germinating mung-bean (Phaseolus aureus) seedlings contained both D- and L-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate (which was characterized by 31P and two-dimensional proton n.m.r.) and D- and/or L-myo-[3H]inositol 1,2,3,4,5-pentakisphosphate; HL60 cells contained myo-[3H]inositol 1,3,4,5,6-pentakisphosphate (in a 500-fold excess over the other species), myo-[3H]inositol 1,2,3,4,6-pentakisphosphate and D- and/or L-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate; and NG-115-401L-C3 cells contained myo-[3H]inositol 1,3,4,5,6-pentakisphosphate (in a 100-fold excess over the other species), D- and/or L-myo-[3H]inositol 1,2,4,5,6-pentakisphosphate, myo-[3H]inositol 1,2,3,4,6-pentakisphosphate and D- and/or L-myo-[3H]inositol 1,2,3,4,5-pentakisphosphate. 2. Multiple soluble ATP-dependent myo-inositol pentakisphosphate kinase activities have been detected in slime mould, rat brain and germinating mung-bean seedling homogenates. In slime-mould cytosolic fractions, the three myo-inositol pentakisphosphates that were present in intact slime moulds could be phosphorylated to myo-[3H]inositol hexakisphosphate: the relative first-order rate constants for these reactions were, in the order listed above, 1:8:31 respectively (with first-order rate constants in the intact cell of 0.1, 0.8 and 3.1 s-1, assuming a cytosolic protein concentration of 50 mg/ml), and the Km values of the activities for their respective inositol phosphate substrates (in the presence of 5 mM-ATP) were 1.6 microM, 3.8 microM and 1.4 microM. At least two forms of myo-inositol pentakisphosphate kinase activity could be resolved from a slime-mould cytosolic fraction by both pharmacological and chromatographic criteria. Rat brain cytosol and a soluble fraction derived from germinating mung-bean seedlings could phosphorylate myo-inositol D/L-1,2,4,5,6-, D/L-1,2,3,4,5-, 1,2,3,4,6- and 1,3,4,5,6-pentakisphosphates to myo-inositol hexakisphosphate: the relative first-order rate constants were 57:27:77:1 respectively for brain cytosol (with first-order rate constants in the intact cell of 0.0041, 0.0019, 0.0056 and 0.000073 s-1 respectively, assuming a cytosolic protein concentration of 50 mg/ml) and 1:11:12:33 respectively for mung-bean cytosol (with first-order rate constants in a supernatant fraction with a protein concentration of 10 mg/ml of 0.0002, 0.0022, 0.0024 and 0.0066 s-1 respectively).

Animals↗
PubMed1991

Genomic imprinting in mammalian development: a parental tug-of-war.

Genomic imprinting in mammals is increasingly being implicated in developmental and pathological processes, but without a clear understanding of its function in normal development. We believe that imprinting has evolved in mammals because of the conflicting interests of maternal and paternal genes in relation to the transfer of nutrients from the mother to her offspring. We present an hypothesis that accounts for many of the observed effects of imprinting in mammals and relates them to similar observations in plants. This hypothesis has implications for studies of X-chromosome inactivation and a range of human diseases.

Animals↗
PubMed1991

Targeting of proteins to the outer envelope membrane uses a different pathway than transport into chloroplasts.

The chloroplastic envelope is composed of two membranes, inner and outer, each with a distinct set of polypeptides. Like proteins in other chloroplastic compartments, most envelope proteins are synthesized in the cytosol and post-translationally imported into chloroplasts. Considerable knowledge has been obtained concerning protein import proteins. We isolated a cDNA clone from pea that encodes a 14-kilodalton outer envelope membrane protein. The precursor form of this protein does not possess a cleavable transit peptide and its import into isolated chloroplasts does not require either ATP or a thermolysin-sensitive component on the chloroplastic surface. These findings, together with similar observations made with a spinach chloroplastic outer membrane protein, led us to propose that proteins destined for the outer membrane of the chloroplastic envelope follow an import pathway distinct from that followed by proteins destined for other chloroplastic compartments.

Adenosine Triphosphate↗