pFJ269, a new plasmid isolated from a beta-lactam antibiotic producing streptomycete.
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Biomedical subjects
Publications and source records attributed to M D Jones.
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Fractures of the first rib may be detected by indirect signs, including apical extrapleural fluid collection, pneumothorax, and supraclavicular soft tissue mass. Thoracic outlet syndrome represents a complex series of abnormalities that may be clarified utilizing digital subtraction angiography. Major distortions of alignment can produce bony adaptive changes at the cervicothoracic junction simulating intra-spinal canal tumors.
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The genome of Epstein-Barr virus is composed of unique DNA interspersed with repetitive sequences. This organization suggests that Epstein-Barr virus provides a useful model for studying the function(s) of repetitive sequences in eukaryotic chromosomes. The primary structure of two of the repeat sequences, the 3072 bp large internal repeat, or BamHI-W repeat, and a smaller 125 bp, G, C-rich NotI repeat, are presented here. Their structures and possible functions are discussed.
Hypertension has only recently been reported in neonatal hyperthyroidism. We describe three children with hypertension as a prominent part of the syndrome. Antihypertensive therapy alone was ineffective in controlling elevated BP. All patients showed gradual resolution of hypertension once a euthyroid state was achieved.
Preliminary data from a study of the effects of anemia on organ blood flow showed large discrepancies between cardiac output measured with the microsphere technique and simultaneous values calculated by the Fick principle. The most likely explanation was that the reference sample drawn according to our standard procedure underestimated the microsphere concentration in arterial blood, resulting in erroneously high blood flow values. In the present experiments we compared our usual reference sample, from a small catheter advanced from a peripheral artery into the brachiocephalic artery (withdrawal rate 1.3 ml/min), with a simultaneous sample from a larger catheter withdrawn at the much higher rate (7.89 ml/min). At hematocrits above 32%, microsphere concentrations from the two catheters were similar, but below 32% the concentration of microspheres in blood from the larger catheter was 30-50% more than from the smaller. The discrepancy was not altered by changing the injection site from left ventricle to left atrium and thus was probably not the result of poor mixing within the heart. It may have been the result of nonhomogeneous distribution of microspheres within larger vessels, perhaps as a consequence of laminar flow and axial streaming of both red blood cells and microspheres during anemia. Whatever the cause, it was possible to eliminate the difference by withdrawing from the smaller catheter at a more rapid rate (2.46 ml/min).
Our previous studies showed that, in contrast to hypoxic and anemic hypoxia, CO hypoxia increased cerebral O2 delivery and decreased cerebral fractional O2 extraction. These changes were correlated with the accompanying decrease in P50 (PO2 at 50% saturation of non-CO bound sites on hemoglobin). To assess directly the role of P50 in the cerebrovascular response to CO, we first performed isovolemic exchange transfusions on unanesthetized newborn lambs, replacing their high-O2-affinity hemoglobin with low-affinity adult sheep donor blood. Exchange transfusion resulted in an average increase in P50 of 10 Torr and in a uniform decrease of regional cerebral blood flow and cerebral O2 delivery of 14%. Thus shifts in P50 can produce cerebrovascular changes during normoxia, implying that the mechanism regulating cerebral blood flow does not have a discrete threshold to an hypoxic stimulus. Induction of CO hypoxia (20-40% carboxyhemoglobin) after the exchange transfusion returned P50 to the control level, and with it restored both cerebral O2 delivery and fractional O2 extraction to the pretransfusion values. We conclude that the fall in P50, rather than a direct tissue effect of CO, is responsible for the relative cerebral overperfusion during CO hypoxia. The importance of the position of oxyhemoglobin dissociation curve as a determinant of cerebral blood flow supports the presence of a highly sensitive, tissue O2-dependent mechanism regulating the cerebral circulation.
We studied the relationship between cerebral oxygen consumption and cerebral oxygen delivery (cerebral blood flow x arterial oxygen content) in fetal, newborn, and adult sheep, Relative to the amount of oxygen consumed, cerebral oxygen delivery in the fetus exceeds that in the lamb and adult by 70 percent. This may represent a protective advantage for the fetus or simply a necessary adaptation to the low arterial oxygen pressure in the intrauterine environment.
An unusual non-defective mutant of polyoma virus with an anomalously large genome, designated din-21, has been isolated. The viral chromosome lacks 49 base pairs of the putative control region between the origin of replication and the initiation codon for the early proteins, the T-antigens. In their stead , 95 base pairs, with limited homology to the deleted sequence and apparently of mouse origin, have been inserted. The primary sequence of the insert DNA has been determined and some of the biological properties of the mutant examined. It transforms rat-1 cells slightly better than wild-type virus and grows slightly less well in lytically infected mouse cells. It does not interfere with the growth of wild-type polyoma virus. The properties of this mutant suggest that it is a natural isolate of mouse cells. The mutant was presumably generated by reciprocal recombination between polyoma DNA and mouse host DNA. This could be associated with the integration of a viral DNA sequence into the host chromosome during the viral replicative cycle.
Developmental effects on the response of cerebral blood flow (Qc) and cerebral O2 consumption (CMRO2) to changes in CO2 tension were assessed in unanesthetized fetal, newborn, and adult sheep. Blood flow was measured using the radioactive microsphere technique. CMRO2 was calculated as the product of Qc and the difference in O2 content between arterial and sagittal sinus blood (CaO2 -- CVO2). The response of Qc to changes in arterial CO2 tension increased from fetus [3.53 +/- 0.56 ml.100 g-1.min-1.mmHg PaCO2(-1) (SE)] to newborn (5.16 +/- 0.59) to adult (6.20 +/- 0.63). Only the fetal-adult difference was significant (P less than 0.05). It has been suggested that developmental differences in CO2 responsiveness of cerebral blood flow are the result of differences in CMRO2. We corrected for differences in CMRO2 by looking at the response to CO2 of the variable 1/(CaO2--CVO2). According to the Fick principle 1/(CaO2--CVO2) = Qc/CMRO2, i.e., blood flow per unit O2 consumption. The fetal response was not significantly different from the newborn, but the adult was significantly different from both (P less than 0.05). Thus the difference in CO2 response of cerebral blood flow between fetus and adult cannot be explained by differences in CMRO2.
In 14 unanesthetized newborn lambs the relationship between cerebral blood flow (measured by radiolabeled microspheres) and arterial O2 saturation (SaO2) was compared during two types of hypoxia: hypoxic hypoxia and carbon monoxide (CO) hypoxia. Cerebral venous samples were obtained from the sagittal sinus. The Increase in blood flow was 47% greater during CO than during hypoxic hypoxia. Cerebral O2 consumption and O2 delivery were constant during hypoxic hypoxia. Thus fractional O2 extraction, which equals O2 consumption/O2 delivery, remained constant with hypoxic hypoxia. During CO hypoxia, although O2 consumption remained constant, O2 delivery increased and fractional O2 extraction decreased. This decline in fractional O2 extraction was correlated with the leftward shift of the oxyhemoglobin dissociation curve that accompanied CO hypoxia. We suggest that cerebral blood flow depends on both SaO2 and the position of the oxyhemoglobin dissociation curve in the newborn lamb. However, this correlation does not exclude other potential histotoxic effects contributing to the relative overperfusion with CO hypoxia.
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The effect of variations in arterial O2 content (CaO2) on the cerebrovascular bed of seven unanesthetized newborn lambs was studied as the hematocrit and arterial PO2 (PaO2) were varied. Each subject was studied at a high hematocrit [44 +/- 3% (SD)] and a low hematocrit [24 +/- 3%]. At each hematocrit level the PaO2 was changed over a range of 30-150 mmHg. The relationship between cerebral blood flow and PO2 depended on hematocrit and vice versa. To the contrary, the relationship of blood flow to CaO2 was independent of hematocrit and/or PO/. As CaO2 fell, regardless of whether this was due to a fall in PO2 hematocrit or both, there was a reciprocal increase in cerebral blood flow such that cerebral O2 delivery (cerebral blood flow x CaO2) was constant. These data show that CaO2 is a variable of fundamental importance to the regulation of cerebral blood flow. Changes in CaO2 are accompanied by reciprocal changes in cerebral blood flow to maintain constant cerebral O2 delivery. Data among species with differing cerebral O2 consumption show that cerebral O2 delivery, in turn, is regulated according to cerebral O2 consumption.
The ontogeny of insulin binding in the sheep was studied using the erythrocytes (RBCs) of 31 fetuses, 10 lambs, and 5 adult animals. Six fetuses were studied on three occasions over a 2-week period from 120--135 days of gestation to provide longitudinal data on changes in insulin binding. Maximal percent binding of [125I]iodoinsulin and receptor concentration decreased significantly as the age of the animal increased (r = 0.76, P less than 0.001 and r = --0.49, P less than 0.001, respectively). Total loss of insulin binding to RBCs was estimated to occur in the second postnatal month, and the RBCs from the adult sheep showed no specific insulin binding. The osmotic fragility of RBCs in each developmental group of animals was also studied to assess possible differences in RBC membrane properties. RBC osmotic fragility was significantly lower in fetuses than in adult sheep (osmotic fragility 50 = 0.55% phosphate-buffered saline vs. 0.76% phosphate-buffered saline, respectively; P less than 0.001). The data suggest that fetal RBCs of lower osmotic fragility and high insulin binding capacity are progressively replaced during late prenatal and early postnatal life by adult-type RBCs of increased osmotic fragility and lacking binding capacity for insulin. The timing of the disappearance of insulin binding to RBCs coincides with the final transition in the animals from a monogastric to a ruminant metabolic state, and may reflect a change in the need for insulin with age.
Sustained and vigorous fetal breathing activity was produced in a chronic fetal lamb preparation by infusion into the fetus of either NH4Cl or HCl. Over a 2 to 3 hour period, 20 to 25 mEq/kg were infused. All of the fetuses tolerated blood pH values of 6.7 to 6.8 and survived. The breathing activity began after the completion of the infusion, and consisted of regular 30 to 50 torr inspirations at a rate of 60 to 120 breaths/min. This activity was continuous for as much as 8 hours, and persisted with pauses and decreased amplitude for 24 to 36 hours. During fetal breathing, blood flow to the diaphragm and intercostal muscles increased approximately 12- and sixfold, respectively.
The amino acid sequence of elongation factor Tu (EF-Tu) from Escherichia coli has been determined. EF-Tu is a single-chain polypeptide composed of 393 amino acids (Mr 43,225 for the species bearing COOH-terminal serine). The NH2-terminal serine is acetylated, and lysine-56 is partially methylated. The sites of facile tryptic cleavage are at arginines 44 and 58 and at lysine-263. The cysteinyl residues associated with aminoacyl-tRNA and guanosine nucleotide binding activities are residues 81 and 137, respectively. The COOH-terminal amino acid is heterogenous in that analyses of the COOH-terminal peptides isolated from different EF-Tu preparations gave position 393 as glycine and serine in ratios (Gly/Ser) ranging from about 0.7 to 3.
Shared-schedule residency training has received more consideration recently as more people have become aware of the need and desirability of such programs. The details of one program, in the Department of Pediatrics of the University of Texas Medical Branch at Galveston, are reviewed. Some of the problems encountered in the execution of this type of program are presented, along with some suggestions for their alleviation. The benefits of a shared-schedule residency are also discussed. The authors suggest guidelines to use in planning a shared-schedule residency program.
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