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Biomedical subjects

M D Jones

Publications and source records attributed to M D Jones.

At least 109 records · Page 6Linked to original sources
PubMed1989

Hypercapnia and response of cerebral blood flow to hypoxia in newborn lambs.

Individual effects of hypoxic hypoxia and hypercapnia on the cerebral circulation are well described, but data on their combined effects are conflicting. We measured the effect of hypoxic hypoxia on cerebral blood flow (CBF) and cerebral O2 consumption during normocapnia (arterial PCO2 = 33 +/- 2 Torr) and during hypercapnia (60 +/- 2 Torr) in seven pentobarbital-anesthetized lambs. Analysis of variance showed that neither the magnitude of the hypoxic CBF response nor cerebral O2 consumption was significantly related to the level of arterial PCO2. To determine whether hypoxic cerebral vasodilation during hypercapnia was restricted by reflex sympathetic stimulation we studied an additional six hypercapnic anesthetized lambs before and after bilateral removal of the superior cervical ganglion. Sympathectomy had no effect on base-line CBF during hypercapnia or on the CBF response to hypoxic hypoxia. We conclude that the effects of hypoxic hypoxia on CBF and cerebral O2 consumption are not significantly altered by moderate hypercapnia in the anesthetized lamb. Furthermore, we found no evidence that hypercapnia results in a reflex increase in sympathetic tone that interferes with the ability of cerebral vessels to dilate during hypoxic hypoxia.

Animals↗
PubMed1989

Cerebral and peripheral circulatory responses to intracranial hypertension in fetal sheep.

Fetal head compression during normal labor can increase intracranial pressure (ICP). We studied the cerebral and peripheral blood flow responses to ICP elevation in utero in chronically catheterized fetal sheep using the radiolabeled microsphere technique. ICP was elevated, stepwise, in increments of 6 +/- 1 mm Hg by infusion of artificial cerebrospinal fluid into a lateral ventricle. When ICP was raised to within 28 mm Hg of baseline mean arterial blood pressure (i.e., ICP above 22 mm Hg), arterial pressure began to increase. Above this ICP level, up to 41 mm Hg, mean cerebral perfusion pressure was maintained by equivalent increases in arterial pressure. Cerebral blood flow and O2 uptake at the highest ICP levels were not different from baseline values. Changes in peripheral organ blood flow were graded according to the level of ICP. At the highest level (ICP = 41 mm Hg), renal, gastrointestinal, and skin blood flow decreased by 68%, 69%, and 65%, respectively. Myocardial and adrenal blood flow doubled, whereas heart rate and cardiac output were unchanged. Placental blood flow increased in proportion to arterial pressure. Arterial plasma epinephrine, norepinephrine and arginine vasopressin increased by nearly two orders of magnitude. Therefore, as ICP approaches baseline mean arterial pressure, fetal lambs are capable of sustaining cerebral perfusion by initiating profound visceral vasoconstriction without curtailing placental blood flow. Since cerebral O2 uptake was maintained, there is no evidence that stimulation of the peripheral response requires pronounced cerebral ischemia. This highly developed Cushing response may be important for ensuring cerebral viability when the fetal head is compressed during parturition.

Animals↗
PubMed1989

Assessing the need for transfusion of premature infants and role of hematocrit, clinical signs, and erythropoietin level.

There are no clear criteria for administration of blood to premature infants. In the past, indications for transfusion have included tachypnea, tachycardia, poor weight gain, apnea, bradycardia, pallor, lethargy, decreased activity, or poor feeding. Some have suggested that erythropoietin levels may also be useful in determining the need for transfusion. Data were studied from 11 premature infants with birth weights less than 1500 g collected throughout 469 hospital days. During that period the infants received a total of 37 blood transfusions. No overall relationship was found between hematocrit of 19% to 64% and heart rate, respiratory rate, or the occurrence of bradycardia; ie, these variables proved to be clinically unreliable as indicators of hematocrit. Furthermore, no predictable effect of transfusion could be identified on heart rate, respiratory rate, or on the incidence of apnea or bradycardia. It was anticipated that frequent episodes of apnea or bradycardia might increase serum erythropoietin concentration. To the contrary, more frequent bradycardia was associated with the low erythropoietin levels because those infants tended to receive transfusions for "symptomatic" anemia. The data are consistent with the concept that "anemia of prematurity" is not predictably associated with symptoms classically attributed to anemia. Possible reasons for this are that the premature infant has a different inherent response to anemia; that it is inappropriate to extrapolate symptoms of severe acute anemia to persons with mild or moderate chronic anemia; or, most likely, that other determinants of heart rate, respiratory rate, and apnea/bradycardia are of more importance than mild or moderate anemia.

Anemia↗
PubMed1988

Determination of clebopride in plasma by capillary gas chromatography-negative-ion chemical ionization mass spectrometry.

A procedure for the analysis of clebopride in plasma using capillary gas chromatography-negative-ion chemical ionization mass spectrometry has been developed. Employing an ethoxy analogue as internal standard, the two compounds were extracted from basified plasma using dichloromethane. Subsequent reaction with heptafluorobutyryl imidazole produced volatile monoheptafluorobutyryl derivatives whose ammonia negative-ion mass spectra proved ideal for selected-ion monitoring. The recovery of clebopride from plasma at 0.536 nmol/l was found to be 85.5 +/- 0.9% (n = 3) whilst measurement down to 0.268 nmol/l was possible with a coefficient of variation of 7.9%. Plasma levels of the compound are reported in two volunteers following ingestion of 1 mg of clebopride as the malate salt.

Antiemetics↗
PubMed1988

Isolation and molecular characterization of a highly polymorphic centromeric tandem repeat in the family Falconidae.

An abundant tandem repeat has been cloned from genomic DNA of the merlin (Falco columbarius). The cloned sequence is 174 bp in length, and maps by in situ hybridization to the centromeric regions of several of the large chromosomes within the merlin karyotype. Complementary sequences have been identified within a variety of falcon species; these sequences are either absent or in very low copy number in the family Accipitridae. The cloned merlin repeat reveals highly polymorphic restriction patterns in the peregrine falcon (Falco peregrinus). These polymorphisms, which have been shown to be stably inherited within a family of captive peregrines, can be used to differentiate the Greenland and Argentina populations of this endangered raptor species.

Animals↗
PubMed1988

A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.

A highly conserved repetitive DNA sequence, (TTAGGG)n, has been isolated from a human recombinant repetitive DNA library. Quantitative hybridization to chromosomes sorted by flow cytometry indicates that comparable amounts of this sequence are present on each human chromosome. Both fluorescent in situ hybridization and BAL-31 nuclease digestion experiments reveal major clusters of this sequence at the telomeres of all human chromosomes. The evolutionary conservation of this DNA sequence, its terminal chromosomal location in a variety of higher eukaryotes (regardless of chromosome number or chromosome length), and its similarity to functional telomeres isolated from lower eukaryotes suggest that this sequence is a functional human telomere.

Base Sequence↗
PubMed1988

Base-line O2 extraction influences cerebral blood flow response to hematocrit.

We have shown that the fall in cerebral blood flow (CBF) as hematocrit (Hct) rises is due to the independent effects of increasing red blood cell (RBC) concentration and arterial O2 content (CaO2). In the present study, we tested the hypothesis that the magnitude of the effect of RBC concentration depends on the base-line cerebral fractional oxygen extraction (E). E is the ratio of O2 demand (cerebral O2 consumption, CMRO2) to supply (cerebral O2 transport: OT = CBF x CaO2) and is assumed to be inversely related to tissue O2 availability. Pentobarbital-anesthetized 1- to 7-day-old sheep were first exchange transfused with plasma to lower Hct to 20%. Base-line E was set to either high or low levels by induction of hypocarbia [arterial CO2 partial pressure (PaCO2) = 15.3 +/- 0.7 mmHg, means +/- SE; n = 7] or hypercarbia (PaCO2 = 62.7 +/- 1.1 mmHg; n = 5), respectively. A second isovolemic exchange transfusion with pure methemoglobin-containing adult sheep red cells then raised Hct (to 38.5 +/- 0.5%) with no significant increase in CaO2. PaCO2 was maintained and other variables (oxyhemoglobin affinity, pH, mean arterial blood pressure) with potential effect on CBF did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗
PubMed1988

Fetal cerebral responses to ventilation and oxygenation in utero.

Previous studies have shown that cerebral oxygen consumption (CMRO2) increases by nearly 50% at birth. The perinatal factors responsible for this increase are unknown; however, one possibility is that fetal CMRO2 is constrained by the normal intrauterine arterial PO2 (PaO2) of approximately 20 mmHg. We investigated this possibility in seven near-term chronically instrumented fetal sheep (131-138 days gestation) in which we inserted vascular catheters and an endotracheal tube. After 1-3 days recovery, we measured cerebral blood flow (CBF) with radiolabeled microspheres and calculated CMRO2. Measurements were made in utero under three conditions for each fetus: 1) nonventilated control; 2) ventilation with 3% O2-5% CO2-92% N2; and 3) ventilation with an inspired oxygen concentration sufficient to raise fetal PaO2 to normal newborn levels (mean 73 mmHg). A calf lung surfactant extract (CLSE) was instilled into the endotracheal tube of the fetus before ventilation to ensure adequate levels of alveolar surfactant and to maintain stable pH and arterial PCO2. The results showed that increasing fetal arterial PO2 to postnatal levels did not consistently increase CMRO2. CBF decreased as arterial O2 content (CaO2) rose, with an inverse hyperbolic response similar to that previously found to relate CBF to CaO2 during fetal hypoxic hypoxia. This indicates that the normally low intrauterine PaO2 does not intrinsically limit CMRO2 and implies that the rapid increase in CMRO2 at birth reflects the activation of specific cellular and physiological processes at (or near) this unique developmental event.

Animals↗
PubMed1988

Bony overgrowths and abnormal calcifications about the spine.

The common phenomenon of osteophyte formation about the vertebral margins and on the vertebral bodies in certain instances connotes underlying disk degeneration. The classification and mechanism of formation of these bony excrescences are not totally clear in all instances, but there is frequent association with degenerative disk change. Distorted alignment of the spinal column as in scoliosis, and functional demands on the spine, play major roles in these abnormalities. The true degree of anatomic abnormality is greater than can be appreciated on the radiographs. Syndesmophytes are vertically orientated outgrowths of trabecular bone forming in the outer margins of the annulus fibrosus and related to repeated episodes of inflammation and repair. They are classically seen in ankylosing spondylitis and colonic spondyloarthropathy. Bulky paravertebral excrescences are more likely to be found in psoriatic arthritis and Reiter's syndrome. Other bony excrescences in the spine were also discussed. OPLL is a progressive disease that can result in severe radicular and myelopathic symptoms. Although OPLL appears to have an unexplained predilection for Asians, it affects all races. Classically diagnosed on lateral radiographs of the cervical spine, it is best imaged with CT. Proper evaluation of the extent of the entire ossified mass and its effect on the spinal cord is crucial in the planning of adequate therapy.

Exostoses↗
PubMed1987

Lack of efficacy of adenosine-5'-monophosphate against HSV-1 ocular shedding in rabbits.

Adenosine-5'-monophosphate (AMP) was evaluated for efficacy in the prevention of spontaneous and induced herpes simplex virus type 1 (HSV-1) ocular shedding in latently infected rabbits with strain McKrae. Intraperitoneal injections (IP) of AMP (100 mg/kg) or NaCl (10 mg/kg) were given on postinoculation (PI) days 16-39. Spontaneous viral shedding was monitored by ocular tear film swabs on PI days 20-39. In the induced rabbits, one group received AMP (IP) and a second group received NaCl (IP) on PI days 66-77. In a third group, AMP (100 mg/kg) was given twice a day IP on PI days 66-77, and AMP was applied by iontophoresis to these eyes on PI days 68-74. In these three groups, ocular viral shedding was induced by ocular iontophoresis of 6-hydroxydopamine on PI day 70 followed by topical application of epinephrine for 5 days (PI days 70-74). HSV-1 ocular shedding was monitored on PI days 66-78. There were no significant differences in spontaneous or induced shedding patterns between the AMP (systemic or systemic plus ocular iontophoresis) and the NaCl groups. These results suggest that this dose of systemically administered AMP plus iontophoresis of AMP does not reduce ocular HSV-1 shedding in rabbits.

Adenosine Monophosphate↗
PubMed1987

Cerebral blood flow autoregulation during intracranial hypertension in hypoxic lambs.

We tested the hypothesis that hypoxic hypoxia interferes with cerebral blood flow (CBF) autoregulation when intracranial pressure (ICP) is elevated in pentobarbital-anesthetized lambs (3 to 9 days old). Cerebral perfusion pressure (CPP) was lowered stepwise from 73 to 23 mmHg in eight normoxic lambs and from 65 to 31 mmHg in eight other hypoxic lambs by ventricular infusion of artificial cerebrospinal fluid. In normoxic lambs, CBF measured by microspheres was not significantly changed over this range of CPP. In animals made hypoxic [arterial O2 tension (PaO2) of 28 Torr; 47% arterial O2 saturation], base-line CBF was twice that of normoxic lambs. CBF was unchanged as CPP was reduced to 31 mmHg. Lower levels of CPP were not attained because a pressor response occurred with further elevations of ICP. No regional decrements in blood flow to cortical arterial watershed areas or to more caudal regions, such as cerebellum, brain stem, or thalamus, were detected with elevated ICP. Cerebral O2 uptake was similar in both groups and did not decrease when CPP was reduced. These results demonstrate that normoxic lambs have a considerable capacity for effective autoregulation of CBF when ICP is elevated. Moreover, cerebral vasodilation in response to a level of hypoxia approximating that normally seen prenatally does not abolish CBF autoregulation when ICP is elevated during the first postnatal week.

Animals↗
PubMed1987

Effect of hematocrit on cerebral blood flow with induced polycythemia.

Cerebral blood flow (CBF) is lowered during polycythemia. Whether this fall is due to an increase in red blood cell concentration (Hct) or to an increase in arterial O2 content (Cao2) is controversial. We examined the independent effects of Hct and Cao2 on CBF as Hct was raised from 30 to 55% in anesthetized 1- to 7-day-old sheep. CBF was measured by the radiolabeled microsphere technique before and after isovolemic exchange transfusion with either oxyhemoglobin-containing erythrocytes (in 5 control animals) or with methemoglobin-containing erythrocytes (in 9 experimental animals). Following exchange transfusion in the control animals, Hct rose (30 +/- 1 vs. 55 +/- 1%, mean +/- SE), Cao2 increased (15.1 +/- 0.8 vs. 26.7 +/- 0.9 vol%), and CBF fell (66 +/- 9 vs. 35 +/- 5 ml X min-1 X 100 g-1). Because the fall in CBF was proportionate to the rise in Cao2, cerebral O2 transport (CBF X Cao2) was unchanged. Following exchange transfusion in the experimental animals, Hct rose (32 +/- 1 vs. 55 +/- 1%) but Cao2 did not change. Nevertheless, CBF still fell (73 +/- 4 vs. 48 +/- 2 ml X min-1 X 100 g-1) and, as a result, cerebral O2 transport also fell. The latter cannot be attributed to a fall in cerebral O2 uptake, as cerebral O2 uptake was unaffected during each of these conditions. Comparison of the two groups of animals showed that approximately 60% of the fall in CBF may be attributed to the increase in red cell concentration alone. It is probable that this effect is due largely to changes in blood viscosity.

Animals↗
PubMed1986

Natural variation of tyrosyl-tRNA synthetase and comparison with engineered mutants.

We report the cloning and sequence analysis of the gene for the tyrosyl-tRNA synthetase from Bacillus caldotenax and properties of the gene product. The amino acid sequence of the tyrosyl-tRNA synthetase was found to be 99% homologous with the corresponding enzyme from B. stearothermophilus, with only four amino acid differences. Two of these natural variations were found to involve active site residues of the enzyme and correspond to mutations that have been engineered previously in vitro. One, Thr-51----Ala-51, produced a more active enzyme, possessing a higher value of kcat/KM for ATP. Position 51 is a "hot spot" in the tyrosyl-tRNA synthetase, differing in enzymes derived from Escherichia coli, B. stearothermophilus, and B. caldotenax. The other, His-48----Asn-48, is found to be a neutral mutation but is in one of the rare regions that are conserved with other aminoacyl-tRNA synthetases. The equivalence of histidine and asparagine at position 48 extends the homology in this region to more enzymes. These residues, His-Ile-Gly-His, and now His-Ile-Gly-Asn, form part of the binding site for ATP in the transition state of the reaction. Although B. caldotenax is an obligate thermophile with an optimal growth temperature of 80 degrees C, as much as 20 degrees C above the growth optima of strains of Bacillus stearothermophilus, its tyrosyl-tRNA synthetase has an identical thermal stability in vitro to that from B. stearothermophilus.

Amino Acid Sequence↗
PubMed1986

Site-specific mutagenesis in vivo by single methylated or deaminated purine bases.

The technique of site-directed mutagenesis has been used to investigate the mutagenicity of O6-methylguanine (O6-MeG) or hypoxanthine introduced as a single lesion at a specific locus in an M13mp9 RF molecule constructed in vitro. Following transformation of O6-MeG-containing RF molecules into E. coli JM101, mutant progeny phage were produced at a frequency not significantly different from that observed with wild-type M13mp9 RF. The mutant yield was greatly enhanced by exhausting cellular O6-MeG DNA-methyltransferase before transformation. In contrast, hypoxanthine exhibited miscoding mutagenesis in the absence of interference with cellular repair mechanisms. This indicates that cellular hypoxanthine-DNA glycosylase acts inefficiently in the removal of hypoxanthine from DNA in vivo. The precise mutational changes induced by hypoxanthine were determined by DNA sequence analysis.

Base Sequence↗