Search PubMed⌕ Search

Biomedical subjects

K A Jones

Publications and source records attributed to K A Jones.

At least 127 records · Page 7Linked to original sources
PubMed1991

Home monitoring of transcutaneous oxygen tension in the early detection of hypoxaemia in infants and young children.

Twenty three patients (age range 0.5-40 months) with recurrent cyanotic episodes underwent physiological recordings, including transcutaneous oxygen tension (TcPO2) from a monitor modified for use at home (Kontron 821S). Of 69 episodes in which the arterial oxygen saturation (SaO2, Nellcor N200) was less than or equal to 80% for greater than or equal to 20 seconds and/or central cyanosis was present, the TcPO2 monitor alarmed (less than or equal to 20 mmHg or 2.67 kPa) in every episode. The pulse oximeter identified hypoxaemia in 62 out of 69 episodes, failing in seven episodes due to signal loss from movement artefact. In only seven of 69 episodes was there an accompanying apnoeic pause (greater than or equal to 20 seconds), and heart rate fell to less than or equal to 80 beats/minute in only five of 28 episodes in which an electrocardiogram was recorded. In 32 episodes in which SaO2 fell to less than or equal to 60%, the TcPO2 monitor alarmed after a median time interval of 16 seconds (maximum time interval 30 seconds). The TcPO2 monitor was then used in an uncontrolled trial at home in 350 patients at increased risk of sudden death and/or hypoxaemia. Indications for monitoring included apparent life threatening events or cyanotic episodes (n = 163), prematurity and prematurity related disorders (n = 86), and sudden unexpected death in one or more siblings (n = 122). The TcPO2 monitor detected cyanotic episodes at home in 81 patients, 52 of whom received vigorous stimulation and/or mouth to mouth resuscitation. Twenty one of these 52 patients had further hypoxaemic episodes documented in hospital with pulse oximetry. In 30 patients, the TcPo2 monitor also identified the gradual development of hypoxaemia, as confirmed by pulse oximetry. Twenty of these needed additional inspired oxygen and six subsequently needed ventilatory support in hospital. This TcPo2 monitor is a reliable detector of both sudden and gradual onset hypoxaemia and is able to be used by parents in the home.

Child, Preschool↗
PubMed1990

Purification of TCF-1 alpha, a T-cell-specific transcription factor that activates the T-cell receptor C alpha gene enhancer in a context-dependent manner.

The differentiation of T cells into functionally diverse subpopulations is controlled in part, by transcriptional activation and silencing; however, little is known in detail about the proteins that influence this developmental process. We have purified a new T-cell-specific factor, TCF-1 alpha, that is implicated in the activation of genes encoding a major component of the human T-cell receptor (TCR). TCF-1 alpha, originally identified and purified through its binding sites on the HIV-1 promoter, was found to bind to the TCR alpha enhancer and to promoters for several genes expressed at significantly earlier stages of T-cell development than the TCR alpha gene (e.g., p56lck and CD3 delta). Sequences related to the TCF-1 alpha binding motif (5'-GGCACCCTTTGA-3') are also found in the human TCR delta (and possibly TCR beta) enhancers. Southwestern and gel renaturation experiments with the use of purified protein fractions revealed that TCF-1 alpha activity is derived from a family of 57- to 53-kD proteins that are abundantly expressed in mature and immature T-cell lines (Jurkat, CCRF-CEM) and not in mature B cells (JY, Namalwa) or nonlymphoid (HeLa) cell lines. A small 95-bp fragment of the TCR alpha control region that contains the TCF-1 alpha binding site juxtaposed between a cAMP-response element (the CRE or T alpha 1 motif) and the binding site for a distinct lymphoid-specific protein (TCF-2 alpha) behaved as a potent T-cell-specific enhancer in vivo. Tandem copies of this enhancer functioned synergistically in mature (Jurkat) T-cell lines as well as resting and activated immature (CCRF-CEM) T-cell lines. Mutation of the TCF-1 alpha binding site diminished enhancer activity and disrupted the synergism observed in vivo between tandem enhancer repeats. The TCF-1 alpha binding site was also required for TCR alpha enhancer activity in transcriptionally active extracts from Jurkat but not HeLa cells, confirming that TCF-1 alpha is a T-cell-specific transcription factor. Curiously, the TCF-1 alpha binding element was inactive in vivo when removed from its neighboring elements on the TCR alpha enhancer and positioned in one or more copies upstream of a heterologous promoter. Thus, the transcriptional activity of TCF-1 alpha appears to depend on the TCF-2 alpha and T alpha 1 (CREB) transcription factors and the context of its binding site within the TCR alpha enhancer.

Base Sequence↗
PubMed1990

The Tecumseh Blood Pressure Study. Normative data on blood pressure self-determination.

In Tecumseh, Mich, we obtained blood pressure (BP) self-determination data in 608 healthy adults (327 men, 281 women; average age, 32.6 +/- 3.5 years) representing a wide range of educational backgrounds. The average (+/- SD) home BP (average 12.7 readings over 1 week) was 120.7/74.8 +/- 10.4/8.6 mm Hg for men and 110.9/69.9 +/- 10.1/7.7 for women. One hundred thirty-three subjects remeasured their home BP 1 year later and a strong correlation between the two readings was obtained (r = .70). Large-scale BP self-determination is feasible. Based on the BP distribution in Tecumseh, the upper limit of normalcy for home BP (2 SDs above the mean) is 142/92 mm Hg for men and 131/85 mm Hg for women.

Adult↗
PubMed1989

In vitro formation of short RNA polymerase II transcripts that terminate within the HIV-1 and HIV-2 promoter-proximal downstream regions.

Trans-activation of HIV-1 transcription by the viral regulatory protein Tat has been proposed recently to overcome a block to RNA polymerase II elongation in vivo imposed by 5'-untranslated leader sequences. Interestingly, however, only full-length transcripts, rather than prematurely terminated HIV RNAs, are synthesized in most cell-free transcription extracts. Here, we describe an in vitro system in which induction of a highly efficient RNA polymerase II termination or cotranscriptional RNA processing event creates short HIV RNAs with 3' ends that map to a region immediately downstream of the HIV-1 or HIV-2 promoters. Termination in vitro is sequence dependent, generating short HIV-1 RNAs of 58-61 nucleotides that resemble in vivo transcripts observed in the absence of Tat, and a distinct, longer transcript of approximately 125-130 nucleotides from the HIV-2 promoter. Deletion of promoter-proximal HIV-2 downstream sequences results in the loss of a discrete RNA but also fails to restore wild-type transcription, indicating that termination actually is specified at the promoter and occurs at a site positioned by one or more elements located immediately upstream of the 3' end of the short RNAs. Experiments with recombinant HIV-2 promoters and nucleoside analogs indicate that this event involves a concerted interaction between the promoter and orientation-dependent leader sequences and that RNA secondary structure formation may also be required. These data provide direct evidence for abbreviated HIV transcripts and an in vitro approach to understanding the roles of cellular and viral regulatory proteins that mediate this process at the HIV promoters.

Adenoviridae↗
PubMed1989

HIV trans-activation and transcription control mechanisms.

Promoter-specific transcription factors, whose function was once thought to be limited to initiation, are now known to have more diverse roles in RNA metabolism, including the cellular localization of transcripts and the integration of RNA initiation with attenuation and RNA 3' end formation. The human immunodeficiency viruses (HIV-1 and HIV-2) provide a useful system to study such proteins, since distinct DNA and RNA elements downstream of the site of transcription initiation act in conjunction with the promoter to regulate the induction and attenuation of RNA synthesis. Sequences corresponding to the 5' untranslated leader of HIV-1 and HIV-2 harbor at least three distinct elements: (i) a DNA domain that binds LBP-1, a cellular activator of initiation; (ii) a structured RNA element critical for the function of the HIV-1 trans-activating protein, Tat; and (iii) an RNA element required for the production of attenuated RNAs from the basal (uninduced) promoter. These attenuated leader RNAs seem to be created in vitro by stalled RNA polymerase II complexes that may be uniquely capable of rapidly processing RNA. Tat-mediated increases in steady-state levels of viral transcripts appear from nuclear run-on experiments to involve a control mechanism at both initiation and early post-initiation steps. Studies that implicate a role for Tat in post-transcriptional control suggest the existence of a mechanism for the coordination of eukaryotic transcription and translation, possibly through the assembly of nuclear regulatory factors at the 5' end of the RNA.

Base Sequence↗
PubMed1988

Structural arrangements of transcription control domains within the 5'-untranslated leader regions of the HIV-1 and HIV-2 promoters.

Promoter-proximal downstream regions of the human immunodeficiency viruses (HIV-1 and HIV-2) mediate the action of the viral transcription activator protein, Tat. We demonstrate here that the downstream domain of each virus interacts with two RNA polymerase II transcription factors. One of these, CTF/NF I, is a multifunctional protein associated previously with activation of transcription and DNA replication. The other cellular protein, designated LBP-1 (leader-binding protein-1), recognizes repeated elements within an extended region of DNA corresponding to part of the 5'-untranslated leader. Analysis of clustered point mutants in the HIV-1 leader for DNA-binding and transcription activity in vitro and in vivo suggests a role for LBP-1 as part of the basal promoter. A complex overlapping arrangement is observed between sequences required for the interaction of LBP-1 and CTF/NF I proteins and those defined previously for regulation by the HIV-1 Tat protein.

Base Sequence↗
PubMed1988

NMDA- and non-NMDA-receptor components of excitatory synaptic potentials recorded from cells in layer V of rat visual cortex.

The pharmacological properties of excitatory synapses on pyramidal cells in layer V of rat visual cortex were investigated by recording EPSPs intracellularly in tissue slices. The EPSPs were evoked by electrically stimulating cells in layer II/III or axons in white matter. All of the layer V neurons were pyramidal in nature as determined by injections of Lucifer yellow or by electrophysiological criteria. Application of the broadly acting antagonists kynurenic acid and gamma-D-glutamylglycine reversibly antagonized the EPSPs from both presynaptic sources in a dose-dependent manner: 1 and 5 mM kynurenic acid produced 63 and 79% reductions, respectively, of control responses. The specific NMDA antagonist APV (50 microM) caused a small reduction in peak amplitude and a more significant reduction in the duration of the falling phase of EPSPs. When slices were bathed in Mg2+-free medium, the amplitude of the EPSP increased substantially. Under these conditions APV reduced the size of the EPSP to that observed with APV in the presence of 1 mM Mg2+. The voltage sensitivities of the APV-sensitive and APV-insensitive components of the layer II/III-evoked EPSPs were examined. The APV-insensitive component was not voltage dependent and had an extrapolated reversal potential of -10 mV. In contrast, the APV-sensitive component showed an NMDA-like voltage dependency; it was greatest at the most positive potentials tested (-45 mV) and nearly absent at membrane potentials below rest. At potentials near threshold, the APV-sensitive component contributed approximately half of the total response. Although the time to peak and decay were longer for the APV-sensitive component, the latency was the same as that of the APV-insensitive component. These results provide evidence that the layer II/III to V pathway, which comprises a major interlaminar circuit in cortex, is mediated directly through NMDA as well as non-NMDA receptors located on the layer V cells. This finding has implications for the role of this circuit in cortical visual plasticity.

2-Amino-5-phosphonovalerate↗
PubMed1987

In vitro activation of the HIV-1 enhancer in extracts from cells treated with a phorbol ester tumor promoter.

The transition from persistent to lytic infection by the human immunodeficiency virus, HIV, is marked by a burst of viral replication and gene expression that occurs when infected cells are stimulated by physiological inducers or tumor promoters like 12-O-tetradecanoyl phorbol acetate (TPA). We report here that the HIV enhancer is activated specifically by TPA in several non-lymphoid cell types, and that this transcriptional regulation can be reproduced in a cell-free system. In vitro transcription experiments revealed a 6-fold activation of the HIV promoter in nuclear extracts prepared from TPA-induced HeLa tk- cells, whereas a control (human alpha-globin) promoter was transcribed with equal efficiency in either induced or uninduced cell extracts. A corresponding increase in the activity of a cellular DNA-binding protein that interacts with the HIV enhancer was detected in TPA-treated cells with DNase I footprint experiments. This increase occurred in the absence of de novo protein synthesis, suggesting a post-transcriptional activation mechanism. Analysis of HIV deletion mutants suggests that the enhancer is the target for the TPA effect both in vitro and in vivo. The cell-free system described here should facilitate studies on the mechanism of phorbol ester induction of gene-specific transcription factors.

Cell Line↗
PubMed1987

31P NMR saturation-transfer measurements in Saccharomyces cerevisiae: characterization of phosphate exchange reactions by iodoacetate and antimycin A inhibition.

31P nuclear magnetic resonance (NMR) saturation-transfer (ST) techniques have been used to measure steady-state flows through phosphate-adenosine 5'-triphosphate (ATP) exchange reactions in glucose-grown derepressed yeast. Our results have revealed that the reactions catalyzed by glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase (GAPDH/PGK) and by the mitochondrial ATPase contribute to the observed ST. Contributions from these reactions were evaluated by performing ST studies under various metabolic conditions in the presence and absence of either iodoacetate, a specific inhibitor of GAPDH, or the respiratory chain inhibitor antimycin A. Intracellular phosphate (Pi) longitudinal relaxation times were determined by performing inversion recovery experiments during steady-state ATP gamma saturation and were used in combination with ST data to determine Pi consumption rates. 13C NMR and O2 electrode measurements were also conducted to monitor changes in rates of glucose consumption and O2 consumption, respectively, under the various metabolic conditions examined. Our results suggest that GAPDH/PGK-catalyzed Pi-ATP exchange is responsible for antimycin-resistant saturation transfer observed in anaerobic and aerobic glucose-fed yeast. Kinetics through GAPDH/PGK were found to depend on metabolic conditions. The coupled system appears to operate in a unidirectional manner during anaerobic glucose metabolism and bidirectionally when the cells are respiring on exogenously supplied ethanol. Additionally, mitochondrial ATPase activity appears to be responsible for the transfer observed in iodoacetate-treated aerobic cells supplied with either glucose or ethanol, with synthesis of ATP occurring unidirectionally.

Adenosine Triphosphate↗
PubMed1987

A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication.

Transcription factor CTF, which is responsible for selective recognition of eukaryotic promoters that contain the sequence CCAAT, was purified to apparent homogeneity by sequence-specific DNA affinity chromatography. Binding sites for CTF in the human Ha-ras and alpha-globin promoters were highly homologous to sequences recognized by nuclear factor I (NF-I), a cellular DNA-binding protein that is required for the initiation of adenovirus DNA replication in vitro. To determine the relationship between CTF and NF-I, we compared the biochemical properties of these two proteins. CTF and NF-I were found to be indistinguishable in polypeptide composition, DNA-binding properties, immunological cross-reactivity, and in vitro stimulation of DNA replication and transcription initiation. We conclude that CTF/NF-I can serve both as a transcription selectivity factor for RNA polymerase II and as an initiation factor for adenovirus DNA replication.

Adenoviruses, Human↗
PubMed1986

Induction of heat shock proteins by canavanine in Tetrahymena. No change in ATP levels measured in vivo by NMR.

During induction of the heat shock response by temperature jump in the protozoan Tetrahymena, a decrease in cellular ATP levels occurs within minutes and cells become thermotolerant. Treatment of Tetrahymena with the amino acid analog canavanine also induces synthesis of heat shock proteins, but more slowly than by temperature jump. No changes in cellular ATP levels were observed during the course of canavanine induction of heat shock protein synthesis measured in vivo by the technique of 31P NMR spectroscopy. Tetrahymena do not become thermotolerant following induction of heat shock protein synthesis with canavanine. However, Tetrahymena will develop thermotolerance in the presence of canavanine if they are first subjected to a nonlethal temperature jump before exposure to a normally lethal temperature.

Acclimatization↗
PubMed1986

Activation of the AIDS retrovirus promoter by the cellular transcription factor, Sp1.

The nature and position of transcriptional control elements responsible for the expression of genes encoded by the retrovirus associated with acquired immune deficiency syndrome (AIDS) have not been precisely defined. In this study it is shown that the mammalian Sp1 transcription factor binds to promoter sequences within the AIDS retrovirus long terminal repeat (LTR) and activates RNA synthesis five- to eightfold in reconstituted reactions in vitro. Experiments in which regions of DNA were protected from added reagents by specifically bound proteins (footprinting) indicated that the upstream promoter region of the AIDS virus LTR lies between -45 and -77 (relative to the RNA start site, +1) and contains three tandem, closely spaced SP1 binding sites of variable affinity. Base-substitution mutations targeted to one or all three Sp1 binding sites were found both to eliminate the binding of Sp1 and to cause up to a tenfold reduction in transcriptional efficiency in vitro. These findings suggest that one important component of the AIDS virus transcriptional control region interacts with a cellular transcription factor, Sp1, and that this factor must function in conjunction with transcriptional elements located downstream of the RNA cap site to mediate the response of the LTR to viral trans-activation.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Postural interneurons in the abdominal nervous system of lobster. I. Organization, morphologies and motor programs for flexion, extension and inhibition.

Using intracellular recording and dye-filling techniques, a survey of postural interneurons was undertaken by impaling their somata in the 2nd abdominal ganglion of lobster. During the course of study approximately fourty different intersegmental interneurons in this ganglion were sampled. Of these, 8 evoked unique, patterned responses in the postural (superficial) motoneurons; each could be identified morphologically. Five of the 8 interneurons had caudally directed axons; 4 of these projected beyond the 4th abdominal ganglion. The remainder projected rostrally, beyond the 1st abdominal ganglion. The postural interneurons were classified according to the motor program they elicited. Five were flexion producing interneurons (FPIs), one was extension producing (EPI), and two generated only inhibitory motor outputs. All motor responses were bilateral and occurred in several segments, including A2. Two neurons, FPIs 201 and 301, produced the full motor reciprocity that typically is observed when flexion command fibers are stimulated. However, three of the FPIs and the single EPI did not express complete reciprocity in synergistic and antagonistic motoneurons. The results indicate that some interneurons displaying all of the properties of command neurons are located entirely within the abdominal nervous system. The overall organization of posture-evoking interneurons appears to be similar to that found in crayfish, suggesting an even more fundamental homology in the neuronal connectivities of these two species than has been established previously.

Abdomen↗
PubMed1986

Postural interneurons in the abdominal nervous system of lobster. II. Evidence for neurons having both command and driver roles.

The nature of the synaptic relationship between 7 identified postural interneurons and 5 pairs of superficial motoneurons was examined by obtaining dual intracellular recordings from interneuron-motoneuron pairs in the lobster 2nd abdominal ganglion. For six different interneuron-motoneuron pairs EPSPs recorded from motoneurons occurred with a short (1 to 3 ms) fixed latency following each presynaptic spike recorded from the interneuron. This suggests that there is a monosynaptic relationship between these interneurons and motoneurons. Monosynaptic pathways accounted for 27% of all excitatory connections. Preliminary evidence indicates that the monosynaptic potentials are mediated by an excitatory chemical synapse since: all IPSPs occurred with latencies greater than 5 ms, there was no evidence for electrical coupling, and one of the interneurons produced facilitating PSPs. A majority of all monosynaptic connections were made by two of the flexion producing interneurons (FPIs), 201 and 301. The synaptic outputs of these FPIs were similar in that both made monosynaptic connections with a different bilaterally homologous pair of motoneurons. Both also produced larger EPSPs and more vigorous spiking in contralateral members of the bilateral motoneuron pairs. A previous study demonstrated that interneurons 201 and 301 are the only postural interneurons yet identified that express motor programs indistinguishable from command neurons. Taken together, these results suggest that certain intersegmental interneurons share properties with command neurons and driver neurons, and that there may not be a sharp morphological or functional distinction between these two cell types.

Abdomen↗
PubMed1986

Postural interneurons in the abdominal nervous system of lobster. III. Pathways mediating intersegmental spread of excitation.

The multisegmented abdomen of crayfish and lobster assumes a variety of postures as components of different behavioral acts. Experimentally these postures can be maintained by activating any of a number of premotor positioning interneurons. The pathways by which the motor output in two or more segments is coordinated were here investigated for a small group of identified postural interneurons whose somata lie in the 2nd abdominal ganglion (A2). Stimulation of all postural interneurons examined evokes a motor output in other abdominal ganglia through which the axon of the neuron passes as well as in the ganglion of origin (ganglion containing the neuron's cell body). The spread of motor excitation away from the originating ganglion occurs via two general pathways. In the first pathway connections to postural motoneurons are made directly by processes of the postural interneuron which pass into ganglia distal to the originating ganglion. Examples of this are shown for two flexion producing interneurons (FPIs) 201 and 301. Each of these FPIs makes monosynaptic connections with motoneurons in A2 and with a homologous set of motoneurons in A3. All postural interneurons fired a set of corollary discharge interneurons (CDIs) whose activities were recorded from the abdominal connectives. Two FPIs, 202 and 301, and a third interneuron, 503, produced motor outputs in ganglia to which they did not project. The motor specificity established in A2 by stimulation of FPIs 202 and 301 (whose axons pass caudally) was preserved in more rostral ganglia, such as A1. Therefore, different sets of CDIs can be specifically recruited to spread the same motor program that is initiated in the originating ganglion to ganglia that do not receive projections from the stimulated postural interneuron. CDIs, in addition, have the capacity to elicit motor programs in distal ganglia that are markedly different from that expressed in the ganglion of origin. For example, although 503 produced an inhibitory output in the abdominal ganglia that it innervated (A1 and A2), a flexion response was generated by it in more caudal ganglia. The caudal flexion response was mediated in part through a monosynaptic activation of FPI 201 and through other unidentified CDIs. Thus, the interneuronal circuitry for postural control is composed of numerous components, some of which have regional control over different portions of the abdominal nerve cord. Depending upon the required movement, select components are coactivated, either serially or in parallel, to effect a variety of spatially distinct positions.

Abdomen↗
PubMed1986

Chronic organic manganese administration in the rat does not damage dopaminergic nigrostriatal neurons.

In an attempt to produce an animal model of Parkinson's disease, we injected rats repeatedly with high doses of methylcyclopentadienyl manganese tricarbonyl (MMT), a compound which has been reported to lower striatal dopamine content in mice. Chronic MMT administration for up to 5 months, even though it produced a substantial elevation in brain manganese content during the period of exposure, did not destroy dopaminergic nigrostriatal neurons. This was assessed by measurements of tyrosine hydroxylase activity and contents of dopamine and its metabolites in the striatum, and by histological examination of the substantia nigra. Our results differ from those of others who administered manganese chloride in drinking water to rats. This discrepancy is unlikely to be a consequence of differences in duration of exposure or route of administration. It could be due to our having used an organic rather than an inorganic manganese compound, or to a species difference in vulnerability to organic manganese between rats and mice.

Animals↗
PubMed1985

In vivo 31P nuclear magnetic resonance saturation transfer measurements of phosphate exchange reactions in the yeast Saccharomyces cerevisiae.

31P saturation transfer techniques have been used to measure phosphate kinetics in the yeast Saccharomyces cerevisiae. The phosphate consumption rate observed in acetate grown mid-log cells was combined with measurements of O2 consumption to yield P/O ratios of 2.2 and 2.9, for cells respiring on glucose and ethanol, respectively. However, no phosphate consumption activity was observed in saturation transfer experiments on anaerobic glucose fed cells. The phosphate consumption rates measured by saturation transfer in cells respiring on glucose and ethanol was attributed to the unidirectional rates of mitochondrial ATP synthesis.

Adenosine Triphosphate↗