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Biomedical subjects

D M Shah

Publications and source records attributed to D M Shah.

At least 217 records · Page 12Linked to original sources
PubMed1983

Genes encoding actin in higher plants: intron positions are highly conserved but the coding sequences are not.

We have isolated actin genes from genomic libraries of two highly diverged plants, maize and soybean. The complete nucleotide sequences of a maize actin gene, MAc1, and a soybean actin gene, SAc1, were determined. The nucleotide sequences of these two actin genes and of a previously sequenced soybean actin gene were compared with the actin gene sequences from a wide spectrum of evolutionarily diverged eukaryotes. Some striking features pertinent to the evolution and function of the plant actin gene families have emerged. The deduced amino acid sequence of the plant actins resembles both cytoplasmic- and muscle-specific actins. DNA sequence analysis as well as genomic blotting experiments using cloned actin sequences as probes show that large sequence heterogeneity exists among members of the plant actin multigene families and between genes from two highly diverged plant species. The sequences of the first nine amino acids at the amino terminal end of the plant actins are far more conserved between distant plant actins than the corresponding sequences in distantly related animal actin genes, suggesting a unique and conserved function for the NH2 terminal sequence in higher plants. The soybean and maize actin genes examined each contain three introns in precisely the same positions, quite contrary to the divergent placement of introns observed in animal, protozoan, and fungal actins. The position of the first intron in soybean and maize actin genes corresponds precisely to the position of an intron found in a nematode actin gene. The position of the second intron coincides with one found in rat and chicken skeletal actin genes. These data suggest that the numerous introns found in all actins are of ancient origin. The degree of silent substitution and replacement substitution was compared among plant actin genes and to those of animal, protozoan, and yeast actin genes. It is clear that the silent substitution sites are saturated among all the genes compared, whereas the replacement sites have diverged in only 5-17% of their possible positions. By these criteria the most distant animal actins are only 6% diverged. The three plant actin genes examined are 8-10% diverged in replacement sites from each other and approximately 14% diverged in replacement sites from any of the animal actins examined. The data in this manuscript suggest that the families of soybean and maize actin genes may have diverged from a single common ancestral actin gene long before the divergence of monocots and dicots.

Actins↗
PubMed1982

Complete nucleotide sequence of a soybean actin gene.

Soybean contains a small multigene family of actin-related sequences. We have determined the complete nucleotide sequence of a soybean actin gene carried on the recombinant plasmid pSAc3. As deduced from the nucleotide sequence, this soybean actin is composed of 376 amino acids. Compared to other eukaryotic actins, pSAc3 actin has a deletion of one amino acid between residues 118 and 122. The initiator methionine is followed by alanine, which is not found at this position in other eukaryotic actins. pSAc3 actin differs, in primary sequence, more from fungal and animal actins than any of the known nonplant actins differ from each other. pSAc3 actin appears to be related to both cytoplasmic and muscle specific actins in the location of specific NH(2)-terminal amino acids. The coding sequence is interrupted by three small introns, each less than 90 base pairs long. The splice junctions are similar to those found in other eukaryotic genes, suggesting the presence of a similar splicing apparatus in higher plants. Introns 1 and 3 interrupt the reading frame after codons 20 and 355, respectively. Intron 2 splits a glycine codon at position 151. None of these intron positions is conserved relative to the positions of introns in other actin genes examined.

Journal Article↗
PubMed1982

Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2 in injured patients.

Post-trauma patients have an oxygen consumption which is proportional to oxygen delivery, suggesting that tissue oxygen consumption is limited by diffusion. Transfusion of packed red blood cells (RBC), which increases the oxygen-carrying capacity of blood, would be expected to increase mixed venous PO2, thereby improving tissue oxygenation. However, the low P50 of stored blood may increase the affinity of hemoglobin for oxygen and reduce oxygen consumption. To evaluate the net effect of these mechanisms, we studied hemodynamic and oxygen transport parameters before and after RBC transfusion in eight critically ill patients. Mixed venous O2 content was measured directly by fuel cell O2 analyzer, and standard P50 was calculated. Following transfusion of one unit of packed RBC which increased mean hemoglobin from 9.2 +/- 0.3 gm/dl to 10.1 +/- 0.3 gm/dl (p less than 0.01), there were no changes in oxygen delivery (490 +/- 80 ml/min/m2), oxygen consumption (210 +/- 30 ml/min/m2), or mixed venous PO/ (37 +/- 2 Torr). Cardiac index (4.1 +/- 0.71 L/min) decreased by 0.4 L/min/m2 (p less than 0.05). Standard P50 decreased by 4.2 +/- 2.4 Torr following transfusion of two units of RBC (p less than 0.05). Red blood cell transfusion thus failed to increase oxygen consumption in these patients, despite an increase in oxygen content. Thus, RBC transfusion may not improve tissue oxygenation.

Adult↗
PubMed1982

Delayed pulmonary dysfunction in head-injured patients.

Intracranial pressure (ICP), cardiopulmonary function, and the degree of neurological dysfunction were measured in 13 patients with serious head injury to determine the relationship of these indices to the development of delayed pulmonary dysfunction. All patients had serious isolated head injury with Glasgow Coma Scale scores of 7 or less 6 hours after injury and elevated ICP at the time of admission to the protocol. Three patients developed arterial pO2 of less than or equal to 80 torr despite the initiation of elevated inspired oxygen fraction (FIO2 greater than or equal to 0.5) and positive end expiratory pressure (greater than or equal to 5 cm H2O. One of these three patients had a decline in neurological function, quantified by the Albany Head-Injury Watch Sheet, associated with hypoxemia. The only patients who developed intrapulmonary shunt fractions of more than 15% were five patients who had increased pulmonary vascular resistance (PVR) and elevated or increasing cardiac index, suggesting persistent perfusion to areas of the lung which normally are hypoperfused due to hypoxic pulmonary vasoconstriction. This mismatching of the distribution of ventilation and perfusion was confirmed using the multiple inert gas elimination technique in two patients with an increased shunt fraction. Unperfused gas exchange units were also found to be present, as confirmed by an abnormal multiple inert gas elimination techniques, high PVR and dead space/tidal volume ratio (VD/VT), and low extravascular lung water. Abnormalities of ICP and cerebral perfusion pressure could not be correlated with changes in any of the cardiopulmonary functions studied.

Adolescent↗
PubMed1982

The nucleotide sequence, expression, and evolution of one member of a multigene family encoding the small subunit of ribulose-1,5-bisphosphate carboxylase in soybean.

We have examined the nuclear genes encoding the small subunit of ribulose-1,5-bisphosphate (RuBP) carboxylase from soybean. One member of this gene family, designated SRS1, has been isolated from a soybean DNA library constructed in the lambda vector Charon 4A. The complete nucleotide sequence and structure of this gene including its two introns and portions of the 5' and 3' flanking sequences were determined. The first exon encodes the entire transit peptide (55 amino acids) and the first 2 amino acids of the mature sequence. Based on analysis of the nucleotide sequence, we concluded that the precursor of the soybean small subunit consists of 178 amino acids. A gene-specific probe for SRS1 was used to show that this gene is transcribed and that steady-state levels of its transcript are strongly light regulated. S1 nuclease mapping was used to locate the potential start of transcription in the sequence and showed that the small subunit gene contains a cap site, TATA box, and -80 sequence, which match the consensus animal sequences. The mature SRS1 small subunit polypeptide of 123 amino acids contains 30 and 34 amino acid replacements relative to the previously determined amino acid sequences from pea and spinach, respectively. Southern blotting of restriction digests of soybean nuclear DNA and data on the complete structure of SRS1 suggest that a multigene family of at least 10 members encodes the RuBP carboxylase small subunit in soybean. Quantitative evolutionary comparison of the soybean small subunit sequence for SRS1 and the pea small subunit sequence suggests that these two genes diverged long before the divergence of pea and soybean.

Amino Acid Sequence↗
PubMed1981

Modified technique to produce valvular incompetence in in situ saphenous vein arterial bypass.

Methods for producing valvular incompetence in the in situ vein arterial bypass have been either traumatic or tedious. We modified the technique of atraumatically incising the venous valves, rendering them incompetent. Using a specially designed long scissors, the valves are excised by introducing the scissors into the proximal end of the vein or, if necessary, one major branch. This requires minimal manipulation and exposure of the vein, almost no disturbance of the venous bed, and makes the operation less tedious.

Femoral Artery↗
PubMed1981

Hypertonic mannitol: its use in the prevention of revascularization syndrome after acute arterial ischemia.

Revascularization of acutely ischemic lower limbs is associated with high mortality and high rates of rethrombosis, limb loss, massive edema, and compartment syndrome. These complications may be due to revascularization syndrome. The effects of hypertonic mannitol used during revascularization of acutely ischemic lower extremities were studied. In an isolated canine hind limb model, revascularization of the limb via a Dacron graft after 90 minutes of ischemia resulted in tissue edema and decreased flow. The low flow state (50% of control) for two hours after reperfusion was associated with thrombosis at the anastomosis. Use of hypertonic mannitol reversed the reperfusion syndrome and prevented graft thrombosis. Therefore, 15 consecutive patients with acute lower extremity ischemia and threatened limb loss were treated with hypertonic mannitol during emergency thromboembolectomy. Fourteen patients survived and had excellent results without any rethrombosis. Compartment syndrome was absent. Results of this clinical trial suggests that hypertonic mannitol may be useful in the management of acute arterial ischemia.

Acute Disease↗
PubMed1981

Defects in peripheral oxygen utilization following trauma and shock.

Following shock and trauma, there may be capillary block or stasis that sets up a neurohumoral response, causing further capillary constriction and ischemia. This ischemia may not result in tissue hypoxia, as functioning capillaries may still exist near the damaged areas. Following resuscitation, however, a reperfusion syndrome causing massive tissue edema, endothelial swelling, and further capillary blocking may lead to tissue hypoxia. We used isolated canine hind limb as a model of the peripheral circulation in a series of experiments that showed that interstitial edema alone did not reproduce the defect in peripheral oxygen utilization. On the other hand, both reperfusion syndrome and microembolization were able to reproduce this response. Hypertonic mannitol and imidazole reversed this defect following either reperfusion syndrome or microembolization, respectively. These data suggest that resuscitated posttrauma patients suffering from defects in peripheral oxygen utilization probably owing to microembolization, reperfusion and tissue edema, which may be treated by specific therapy.

Animals↗
PubMed1981

Use of isovolemic hemodilution in the management of arterial ischemia in patients with polycythemia.

The management of patients with both polycythemia and limb-threatening ischemia presents many difficulties because in this population, vascular surgical procedures carry a particularly high incidence of hemorrhagic and thromboembolic complications. We evaluated the use of acute isovolemic hemodilution in 12 polycythemic patients who required urgent surgery due to severe ischemia and threatened limb loss. Within 48 hours, blood was withdrawn in units of 500 ml and simultaneously replaced with 1,500 ml of lactated Ringer's solution until a hematocrit of 35 to 40 percent was achieved. After hemodilution, two patients had such a marked improvement that no further therapeutic measures were required immediately. Four patients showed definite improvement in pulmonary vascular resistance tracings and segmental Doppler pressures, but ischemia was not fully ameliorated. These patients together with the remaining six patients underwent vascular surgery within 1 to 14 days after hemodilution. A hematocrit of 32 to 40 percent was maintained during the perioperative period. All arterial reconstructions were successfully completed and there were no perioperative failures. No pulmonary emboli, myocardial infarctions, or deaths occurred in this period. These results indicate that in polycythemic patients, urgent vascular surgery can be performed more safely with the concomitant use of acute isovolemic hemodilution.

Aged↗
PubMed1981

Further experience with the saphenous vein used in situ for arterial bypass.

Ongoing experience with use of the saphenous vein in situ as in infrainguinal arterial bypass is presented. One hundred eighty-three bypasses were performed for limb-threatening ischemia, 92 of which were to the popliteal artery, either isolated or in continuity with one or more tibial vessels, and 91 bypasses were carried to single tibial vessels below the termination of the popliteal artery. The results were analyzed by the life table method and show an overall patency rate of 89.8 percent at 3 to 4 years. Separate life table analysis of the tibial bypass group showed a patency rate of 83 percent at 3 to 4 years. Special emphasis is placed on the ability to use veins less than 4 mm in diameter, which comprise 40 percent of those used in these procedures. The superior results provided by the in situ method are explained in part by experimental observations which show that endothelial stability is completely preserved by this method but is severely disturbed during the process of vein removal and reversal.

Aged↗
PubMed1981

Multigene family of actin-related sequences isolated from a soybean genomic library.

We have investigated the actin-related sequences in soybean using heterologous actin DNA probes from Dictyostelium, Drosophila, and yeast. Southern blot analysis of restriction digests of soybean DNA indicates that actin is encoded in a small multigene family. In order to isolate individual members of this gene family, we have constructed a soybean genomic library in the lambda vehicle Charon 4A. A partial characterization of this library shows it to be nearly complete. We have isolated from this library a number of recombinant clones that hybridize to actin-coding sequences from all three heterologous probes. We have identified the fragments containing the actin-related sequences on the physical maps of two of these clones lambda SAc1 and lambda SAc3. These fragments were subcloned in the plasmid vehicle pBR322. Using electron microscope heteroduplex mapping we show that the subclones, pSAc1 and pSAc3, share homology with the entire actin-coding sequence (1.1 kb) of Drosophila and Dictyostelium. Furthermore, pSAc1 and pSAc3 have additional homology of approximately 0.22 kb at the 5' ends of their coding sequences. No homology is detected in the 3' flanking regions of these clones. The actin sequence in pSAc1 contains an interruption of approximately 0.30 kb located 0.39 kb from the 5' end of the actin polypeptide coding region.

Actins↗
PubMed1981

Effect of external pressure on axillofemoral bypass grafts.

External compression of axillofemoral grafts has been suggested many times as a cause for graft thrombosis. Thrombosis during sleep is the most common presentation of axillofemoral graft failure. Therefore, external compression of the graft by the body weight has been implicated in graft thrombosis. Six consecutive patients with axillofemoral bypass grafts for aortoiliac disease were studied on routine clinic visits. Pulsatile flow characteristics were studied by pulse volume recordings (PVR) and segmental Doppler pressure measurements in calf and ankle, prior to and during attempted graft compression, by having the patient lay on the graft. External compression by body weight did not alter the PVR and segmental Doppler pressure (P = NS) in the distal circulation. Therefore, these data suggest that external compression by the body weight may not be the primary cause of graft failure.

Axillary Artery↗
PubMed1981

A system to measure functional residual capacity in critically ill patients.

The use of continuous positive airway pressure (CPAP) and intermittent mandatory ventilation (IMV) in spontaneously breathing, intubated patients has prompted the development of new procedures for measuring functional residual capacity (FRC). The authors have developed a system for measuring FRC by the multiple breath nitrogen washout technique, which is suitable for use on intubated patients breathing with CPAP, IMV, or intermittent positive pressure ventilation (CONTROL) and on nonintubated patients. This system uses a pair of synchronized volume ventilators to permit a step change in inspired N2 fraction while providing therapeutic ventilatory support. A rapid-response nitrogen analyzer and a modified bellows spirometer are used for continuous measurement of airway nitrogen concentration and expired gas flow rate. FRC is calculated on-line by a digital computer. The system accuracy was tested on a mechanical lung simulator in the CPAP and CONTROL modes. The measured volume was found to agree within 58 +/- 52 ml of the actual volume in the CONTROL mode and within 104 +/- 22 ml in the CPAP mode. The system was also tested for repeatability by making duplicate FRC determinations in patients with respiratory insufficiency. In the 18 patients studied, the correlation coefficient of these duplicate measurements was r = 0.987 and the mean difference between measurements was 49 +/- 24 ml. This noninvasive system also provides data used to calculate anatomical deadspace by Fowler's method (VSDS) and uniformity of ventilation (V/V) for multicompartment lung models.

Functional Residual Capacity↗
PubMed1981

Nitroprusside and nitroglycerine in patients with posttraumatic pulmonary failure.

Pulmonary artery pressure is frequently elevated in patients with post-traumatic pulmonary dysfunction. To ascertain whether or not this increase is reversible and what effects such reversal would have on gas exchange, the vasodilators nitroprusside and nitroglycerine were administered to 11 such patients. Pulmonary hemodynamics an gas exchange were observed. Mean pulmonary artery pressure and pulmonary vascular resistance decreased and pulmonary shunt increased. Cardiac output did not change. These results imply that much of the increase in pulmonary artery pressure is due to a reversible restriction of blood flow past unventilated alveoli. Hypoxic vasoconstriction is postulated to be a major cause of the increase in pulmonary artery pressure.

Blood Pressure↗