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Biomedical subjects

M D Jones

Publications and source records attributed to M D Jones.

At least 19 recordsLinked to original sources

Randomised controlled trial of day care for hypertension in pregnancy.

Our aim was to assess the effect of the introduction of a day-care unit on the care of women with non-proteinuric hypertension in pregnancy. A randomised controlled trial was carried out on 54 women who presented at 26 weeks of pregnancy or later with non-proteinuric hypertension (systolic blood pressure 150-170 mm Hg and/or diastolic pressure 90-105 mm Hg on two occasions at least 15 min apart). 30 women were allocated to care by the day unit and 24 were managed according to the established practice of their clinicians without access to the day unit (control group). Women in the control group spent on average 4.6 times longer as inpatients (difference in mean stay 4.0 days [95% confidence interval 2.1-5.9 days]) than the day-unit group and were 8.8 times (95% CI 3.0-25.8) more likely to be admitted to hospital. Induction of labour was 4.9 times (95% CI 1.6-13.8) more likely in the control than in the day-unit group and the development of proteinuria 11.4 times (95% CI 1.8-71.4) more likely. The control group had a mean of 1.5 fewer hospital outpatient visits (95% CI 0.36-2.64). The groups did not differ in their use of antihypertensive drugs. Day-unit care for hypertension in pregnancy significantly reduced the need for and the length of antenatal inpatient admissions and the number of medical interventions, at the cost of an increase in outpatient attendances. Our results are further evidence that inpatient care does not improve outcomes or prevent the development of proteinuria in this disorder.

Adult

Alternative splicing determines the carboxy terminus of the Epstein-Barr virus nuclear antigen 5 species expressed in the Burkitt's lymphoma cell line Daudi.

The Daudi strain of Epstein-Barr virus (EBV) possesses a genomic deletion, relative to the B95-8 EBV prototype, that removes the entire Epstein-Barr virus nuclear antigen 2 (EBNA2) open reading frame (ORF) and the sequences encoding the carboxy terminus of EBNA5. Immunoblot analysis carried out in this study indicates that two species of EBNA5 (31K and 37K) are expressed in Daudi cells. Nucleotide sequence analysis of Daudi cDNA clones has confirmed that, as a consequence of the genomic deletion, exons usually appearing further downstream in EBNA messages (exons U or HF) are spliced directly onto the truncated EBNA5 ORF. Furthermore, the use of alternative splicing suggests that the two EBNA5 species expressed in Daudi cells possess different carboxy termini.

Alternative Splicing

Circulatory dynamics during periodic intracranial hypertension in fetal sheep.

The human fetal head is periodically compressed during labor. The resulting increase in intracranial pressure (ICP) may exceed the hydrostatic increase in mean arterial pressure (MAP), thereby decreasing cerebral perfusion pressure (CPP). We determined whether the cardiovascular system of near-term fetal sheep is capable of rapidly increasing MAP during periodic increases in ICP. In 12 chronically instrumented fetuses, we produced sinusoidal oscillations in ICP with a maximum of 52 +/- 1 mmHg (baseline MAP) and a minimum of 4 +/- 1 mmHg at a 3-min periodicity by ventricular fluid infusion and withdrawal. Phasic increases in MAP and decreases in electromagnetically determined renal blood flow tracked behind ICP by 0.3-0.5 min. By the sixth cycle, tonic peripheral vasoconstriction that occurred attenuated by the reduction in CPP during subsequent ICP oscillations. By the 10th cycle, plasma catecholamines and vasopressin increased 20-fold. To more closely simulate the pattern during labor, we produced an ICP triangular pulse train with 5-min periodicity and pulse duration of 1.5 min in six other fetuses. The MAP response was nearly out of phase with this more rapid rise of ICP. Thus the phasic component of the fetal pressor response is inadequate for maintaining CPP when ICP is increased to baseline MAP in less than 0.75 min. However, when the ICP pulse duration and frequency are sufficiently high, a tonic pressor response that may be humorally mediated acts to minimize transient cerebral ischemia.

Animals

Oxygen free radicals and the cerebral arteriolar response to group B streptococci.

We used a cranial window preparation to observe the effects of direct application of group B streptococci to the surface of the brain in the adult rat. Continuous exposure to group B streptococci at concentrations of 10(3) and 10(5) organisms/mL caused progressive dilation of surface (pial) cerebral arterioles that became statistically significant (p less than 0.05) after 2.5 h. These results were reproduced with heat-killed organisms at the same concentration, but not with a bacteria-free filtrate of the growth medium. In separate studies, we found that infusion of alkaline cerebrospinal fluid (pH = 7.8) into the window did not reverse vasodilation, suggesting that it was not due to progressive cerebrospinal fluid acidosis. A solution of nitroblue tetrazolium infused into the window at the end of a 3-h exposure to the organism was promptly reduced, suggesting the presence of oxygen free radicals. Treatment with i.v. polyethylene glycol-superoxide dismutase and polyethylene glycol-catalase in doses of 10,000 and 20,000 U/kg, respectively, was itself without effect on pial arterioles, but treatment with these compounds before exposure to group B streptococci eliminated the vasodilation. These data support a role for oxygen free radicals in the pathogenesis of pial arteriolar dysfunction induced by exposure to group B streptococci.

Animals

The genome of human herpesvirus 6: maps of unit-length and concatemeric genomes for nine restriction endonucleases.

More than 50 fragments resulting from complete digestion of the DNA of human herpesvirus 6 (HHV-6, strain U1102) with BamHI, EcoRI, HindIII, KpnI, NruI, SalI or SmaI have been isolated as clones in M13, plasmid, cosmid and lambda vectors. Using these clones, maps have been constructed for the fragments produced by nine restriction enzymes from unit-length virus genomes and from their concatemeric precursors. The unit-length genome is a linear, double-stranded molecule of 161.5 kbp composed of a central segment of a largely unique sequence of 141 kbp (U) with a sequence of 10 kbp duplicated in the same orientation at both 'left' and 'right' genomic termini (i.e. 'left' and 'right' copies of the direct repeat; DRL and DRR). Adopting as standard an orientation in which the major capsid protein gene is 'left' of the gene for alkaline exonuclease, then the 'right' genome termini and DRL. U junctions occur close to or within repetitive (GGGTTA)n sequences. Repetitions of short sequence motifs are present in at least two other regions of the genome. One of these regions consists of a simple repeat (TC/G) of approximately 1.5 kbp in length and is unstable as clones in bacterial vectors. The second region is stably maintained in such vectors and consists of a tandem array of at least 25 copies of a 110 bp sequence containing a single KpnI site. Comparisons of fragments arising from unit-length DNA with those from virus DNA from the nuclei of infected cells have shown that the concatemeric junctions in intracellular DNA contain head-to-tail dimers of the terminal duplications (i.e. ...U1.DRR1.DRL2.U2...). The gross structure established here for the genome from the U1102 isolate of HHV-6 resembles closely that suggested by Pellett and his colleagues for the Z29 isolate and differs from that of the five previously characterized human herpesviruses. This structure of HHV-6 DNA bears a superficial resemblance to that proposed for DNA from channel catfish virus and equine cytomegalovirus.

Base Sequence

Characterization of the DNA polymerase gene of human herpesvirus 6.

The construction of a recombinant bacteriophage lambda library containing overlapping clones covering 155 kbp of the 161-kbp genome of the Ugandan U1102 isolate of human herpesvirus 6 (HHV-6) is described. The use of degenerate-primer polymerase chain reaction allowed the isolation of a DNA probe for the DNA polymerase gene of HHV-6, which was subsequently used to isolate and position the pol gene on the physical map of the viral genome. A 4.4-kbp EcoRI DNA restriction fragment containing the pol gene was isolated and sequenced. The open reading frames flanking the pol gene code for the HHV-6 glycoprotein B gene and the human cytomegalovirus UL53 homolog. This arrangement is different from that seen in the alpha and gamma herpesvirus families, lending further support to the notion that HHV-6 is a member of the beta herpesvirus group.

Amino Acid Sequence

Redistribution of cardiac output and oxygen delivery in the hypoxemic fetal lamb.

In hypoxia, fetal cardiac output and the product arterial O2 content x blood flow to the fetal heart and central nervous system (CNS) tend to remain constant. As a consequence the percentage of cardiac output directed to the heart and CNS increases hyperbolically in inverse relation to the oxygen content of the fetal ascending aorta, [O2]as. The fetal lamb maintains [O2]as approximately 0.45 mM (0.45 +/- 0.02 SEM) higher than the O2 content in the abdominal aorta, [O2]ab, over a wide range of oxygenation. When [O2]as decreases below the 2 mM level, the [O2]as--[O2]ab difference (delta O2) decreases also. A mathematical model of the fetal circulation shows that delta O2 is a function of the ratio oxygen consumption of fetal upper body/abdominal aorta blood flow (VU/FA). The behavior of delta O2 in hypoxia can be explained by assuming that the VU/FA ratio is maintained in moderate hypoxia and decreases in sever hypoxia.

Animals

Blood flow to fetal organs as a function of arterial oxygen content.

In a sheep preparation the blood flow to fetal organs was studied 3 to 10 days after surgery by means of the microsphere technique over a range of fetal arterial O2 content from 6 to 1 mM. Blood flows to neural tissues (cerebrum, cerebellum, brain stem), heart, and the adrenals increased in inverse relation to arterial O2 content. As a result the arterial supply of O2 to these organs tended to remain constant over the O2 range studied. Blood flow to the fetal lungs decreased progressively with hypoxia. The blood flow to kidneys, digestive tract, pancreas, and carcass had a tendency to remain constant or increase gradually in the transition from high to moderately low levels of arterial O2 content and then to decrease abruptly in more severe hypoxia. Umbilical blood flow did not change systematically in relation to arterial O2 content.

Acid-Base Equilibrium

Lap-sash three point seat belt fractures of the cervical spine.

Cervical spine injuries associated with three-point fixation lap-sash seat belts result from impact against the sash. While such injuries are infrequent and often without serious neurologic sequelae, they may produce serious deficits with grave injuries. Flexion-extension fractures of the lower cervical vertebrae, fractures of the transverse and spinous processes of the lower cervical and uppermost thoracic vertebrae, discal disruptions, and brachial plexus avulsions may occur. Of the 3 patients reported here, 2 escaped serious damage.

Accidents, Traffic

Regulation of cerebral blood flow in the ovine fetus.

The effects on fetal cerebral blood flow (Qc) of changes in the carotid arterial and sagittal sinus venous PO2, PCO2, and oxygen content were studied in the chronically catheterized ovine fetus in utero at 130-140 days of gestation. Forty-seven measurements of Qc were made in 20 fetuses with radioactive microspheres. In 11 of these animals, 84 measurements of cerebral arteriovenous differences of oxygen content were performed, permitting an indirect measurement of cerebral blood flow (Qc*), assuming a constant cerebral metabolic rate. Arterial and, in 11 animals, sagittal sinus blood was withdrawn for analysis of PO2, PCO2, oxygen content, and pH at the time of the flow measurements. Preliminary analysis showed the best predictor of Qc and Qc* to be the reciprocal of the arterial oxygen content (1/CaO2). Multiple linear regression analysis combining the effects of 1/CaO2 with arterial PCO2 (PaCO2) gave the following equations: Qc = 458.8 (1/CaO2) + 2.68 PaCO2 - 107.93 (R2 = 0.68); Qc* = 435.54 (1CaO2) + 2.20 PaCO2 - 75.03 (R2 = 0.86). As a result of the hyperbolic relationship between Qc (and Qc*) and CaO2, changes in CaO2 at the low levels found during intrauterine life exert an important influence on the fetal cerebral circulation.

Animals

Insulin effect on fetal glucose utilization.

Insulin infused into a sheep fetus over a 3-hr period at the rate of approximately 0.24 U.kg-1.h-1 increased fetal glucose uptake (utilization) from 4.4 +/- 0.7 mg.min-1.kg-1 to 6.9 +/- 0.9 mg.min-1.kg-1 as compared to a noninsulin control period. Insulin administration did not alter fetal oxygen consumption (8.6 +/- 0.7 ml.min-1.kg-1 vs. 7.7 +/- 0.7 ml.min-1.kg-1), umbilical blood flow (220 +/- 1 ml.min-1.kg-1 vs. 209 +/- 16 ml.min-1.kg-1), or the placental clearances of antipyrine (114 +/- 7 ml.min-1.kg-1 vs. 109 +/- 8ml.min-1.kg-1) and urea (24.5 +/- 2.2 ml.min-1.kg-1 vs. 25.0 +/- 2.1 ml.min-1.kg-1). Fetal plasma glucose concentration fell significantly (0.22 +/- 0.01 mg.ml-1 to 0.16 +/- 0.01 mg.ml-1) during insulin infusion. The insulin effect on fetal glucose uptake occurred over a range of maternal glucose concentrations (0.32 leads to 0.78 mg.ml-1), which were not altered by the infusion of insulin in the fetal compartment. Insulin has a specific effect on increasing fetal glucose uptake and utilization.

Animals