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Biomedical subjects

R E Ward

Publications and source records attributed to R E Ward.

At least 55 records · Page 3Linked to original sources
PubMed1990

Mutational alteration of the breakage/resealing subunit of bacteriophage T4 DNA topoisomerase confers resistance to antitumor agent m-AMSA.

Bacteriophage T4 provides a simple model system in which to examine the mechanism of action of antitumor agents that have been proposed to attack type II DNA topoisomerases. Prior results demonstrated that T4 type II DNA topoisomerase is the target of antitumor agent 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) in phage-infected Escherichia coli: a point mutation in topoisomerase structural gene 39 was shown to confer both m-AMSA-resistant phage growth and m-AMSA-insensitive topoisomerase activity. We report here that a point mutation in T4 topoisomerase structural gene 52 can also independently render both phage growth and topoisomerase activity resistant to m-AMSA. The DNA relaxation and DNA cleavage activities of this newly isolated mutant topoisomerase were significantly insensitive to m-AMSA. The drug-resistance mutation in gene 52, as well as that in gene 39, alters the DNA cleavage site specificity of wild-type T4 topoisomerase. This finding is consistent with a mechanism of drug action in which both topoisomerase and DNA participate in formation of the drug-binding site.

Amsacrine↗
PubMed1990

Increased septic complications with three-drug sequential immunosuppression for cadaver renal transplants.

In 152 renal transplant recipients, the results of immunosuppression with three-drug sequential (Minnesota antilymphocyte globulin, prednisone, azathioprine, and cyclosporine) immunosuppression (n = 107) were compared with those of a two-drug sequential protocol (Minnesota antilymphocyte globulin, prednisone, and cyclosporine) that excluded azathioprine (n = 45). The study groups were comparable by age, sex, etiology of renal failure, incidence of diabetes, and degree of HLA matching. Patient survival at 1 year was not significantly different in the two groups (two drug, 93% versus three drug, 86%; p = 0.19). One-year graft survival was superior in the two-drug group (two drug, 93% versus three drug, 75%; p = 0.02). Analysis of primary transplants only (n = 116) yielded the same results. During the first year, the serum creatinine level remained stable in both groups. As expected, the three-drug therapy group had significantly more bacterial and viral infections. For low-risk primary cadaveric renal transplants, two-drug sequential immunosuppression is superior.

Adult↗
PubMed1990

A simplified method for bilateral aortorenal bypass.

We recommend this technical improvement for instances requiring bilateral renal arterial bypass. The technique of aortorenal bypass for bilateral renal arterial stenosis using a side to side bridging aortic-saphenous vein graft followed by bilateral end to side saphenous vein to renal arterial anastomosis has been described herein.

Anastomosis, Surgical↗
PubMed1989

Successful atrial caval shunting in the management of retrohepatic venous injuries.

Over a 3-year period, 519 patients underwent laparotomy for liver injuries. Nine (2 percent) required insertion of an atrial caval catheter to control hemorrhage from perihepatic venous injuries. In three cases, the shunt arrested the hemorrhage, allowing successful surgical repair of the venous injuries. From a careful analysis of our experience, we have identified common errors made in shunt placement, developed a modified atrial caval catheter, and have simplified the surgical technique for insertion.

Adolescent↗
PubMed1989

Pretransplant hyperthermia promotes permanent survival of murine thyroid allografts.

Hyperthermic treatment of skin has been shown to abolish stimulation of allogeneic lymphocytes in a mixed skin-lymphocyte reaction. These experiments test the hypothesis that hyperthermic pretreatment of endocrine tissue can promote its permanent survival in allogeneic recipients. Murine thyroid tissues were treated at 37, 43, or 45 degrees C for 0.5-4.0 hr and transplanted to the left renal capsule of recipient mice. Graft survival was determined after 100 days by the ratio of counts between the left and right kidneys 24 hr after administration of 0.5 microCi 125I. Balb/c recipients of C57BL/6 thyroids treated at 43 degrees C for 2 or 4 hr had viable grafts in 4/7 (P = 0.032) and 4/5 (P = 0.015) cases, respectively, compared to controls (0/10). C57BL/6 recipients of Balb/c thyroid treated at 43 degrees C for 4 hr had viable grafts in 6/10 cases (P = 0.009) compared to control (0/10). Treatment at 45 degrees C was lethal, evidenced by failure of all isografts. Pretransplant treatment at 43 degrees C promotes permanent thyroid allograft survival without immunosuppression.

Animals↗
PubMed1989

Schistosoma mansoni: migration and attrition of challenge parasites in naive rats and rats protected with vaccine serum.

The migration of isotopically labelled Schistosoma mansoni challenge cercariae was monitored, by means of squashed organ autoradiography, in naive Sprague-Dawley rats and rats protected with serum harvested from twice vaccinated donors. The majority of challenge larvae migrated from the skin to the lungs in both groups of rats, but a significantly increased number of larvae was retained in the lungs of serum recipients on day 8 post-challenge. An average of 25% of the challenge population succeeded in migrating to the livers of naive rats by day 14, compared to only 13% in passively protected animals; serum recipients were shown by perfusion on day 21 to be 73% immune. Histological examination of lung tissue harvested from naive rats challenged intravenously with lung-stage schistosomes revealed small foci composed of mononuclear cells that sometimes enclosed larvae; these worms are likely to be lost due to innate resistance. In the lungs of serum-protected rats, many challenge larvae were seen to be surrounded by extensive eosinophil-enriched inflammatory foci; parasite remnants were also observed within such reactions. Ultrastructural examination of worms recovered from the lungs of passively protected animals revealed muscle disruption and internal vacuolation, although the tegument remained intact. It is proposed that challenge attrition in serum-protected rats occurs essentially in the lungs and involves larval immobilization and subsequent death, perhaps mediated by cellular mechanisms.

Animals↗
PubMed1989

Tc-NGA imaging in liver transplantation: preliminary clinical experience.

Technetium-99m galactosyl-neoglycoalbumin (Tc-NGA) is a new liver imaging agent that binds to hepatic-binding protein, a hepatocyte-specific membrane receptor. The purpose of this study was to determine the potential of Tc-NGA imaging in clinical liver transplantation. A total of 25 studies were performed in nine patients. Imaging studies performed in the early posttransplant period in patients with good hepatic allograft function revealed diffuse patchiness in tracer distribution, a manifestation of preservation damage. Left lobar infarction was demonstrated within a few hours of ischemic injury. Right posterior segmental infarction was seen in another patient. Comparison of kinetic, clinical, and biochemical data revealed good correlation between hepatic allograft function and Tc-NGA kinetics. Major kinetic alterations were noted during periods of preservation injury, hepatic infarction, and acute rejection. These studies indicate: (1) major alterations in Tc-NGA kinetics occur during preservation injury, hepatic infarction, and acute rejection, and (2) Tc-NGA kinetic data appear to provide an accurate reflection of hepatic allograft function. Tc-NGA imaging has the advantages of being noninvasive and of utilizing standard nuclear medicine instrumentation, including portable imaging devices. In conclusion, Tc-NGA imaging provides a promising noninvasive approach for evaluation of liver function in patients undergoing hepatic transplantation.

Adult↗
PubMed1989

Facial morphology as determined by anthropometry: keeping it simple.

Anthropometry remains an efficient, noninvasive method for describing craniofacial morphology in spite of the appearance of more sophisticated technologies. The major advantage afforded by anthropometry is its technical simplicity, a fact which makes it a readily available tool for evaluating patients, planning facial surgery, or delineating basic features of craniofacial syndromes. Anthropometry lacks the detail of more powerful technologies, but it is better suited for populational studies because of the availability of comparative, normal databases. The standard z-scores produced by such comparisons lend themselves to multivariate analysis. This type of comparative analysis is not yet possible for computerized tomography, three-dimensional imaging, or photogrammetry. To illustrate the utility of this technique an example is cited from an ongoing study of hypohidrotic ectodermal dysplasia (HED) in which anthropometry reveals details of facial morphology overlooked in previous studies. These include the presence of reduced facial height and a striking reduction in the size of the facial features in spite of the fact that facial widths are comparatively normal. Gene carriers show a similar though nonidentical pattern of defects. Like all morphometric approaches, anthropometry has its limitations. Well-designed protocols minimize these limitations by incorporating multiple facial dimensions in the analysis and by emphasizing careful collection of data with standard instruments and methodology.

Cephalometry↗
PubMed1989

A study of cephalometric features in cleft lip-cleft palate families. I: Phenotypic heterogeneity and genetic predisposition in parents of sporadic cases.

Several previous studies have indicated that unaffected parents of children with nonsyndromic cleft lip and palate show unusual craniofacial features. This study reexamines this question by applying multivariate cluster analysis to lateral cephalometric head plates from 82 individuals who are parents of sporadic cases of cleft lip with or without cleft palate (CL/P). Considerable phenotypic heterogeneity was present within the sample. Three major groupings were defined. Two of these groups showed cephalometric similarities to individuals with overt clefts, while the third showed a generalized concordance to published norms. In almost every case only one member of each parental pair showed the cleft related cephalometric phenotype, suggesting the possibility of a substantial genetic component in many cases of sporadic CL/P. However, there were several cases in which neither parent showed the phenotypic traits. Such cases may have a different etiology or a greater environmental component.

Adult↗
PubMed1988

Regulation of an idiotype+ B cell lymphoma. Effects of antigen and anti-idiotopic antibodies on proliferation and Ig secretion.

The B cell surface Ig molecule plays an important regulatory role in delivering inductive/tolerogenic signals to the cell. In this paper, the effect of Ag and anti-idiotopic antibodies on the in vitro proliferation and Ig secretion of a B cell tumor was studied. The tumor (BCL1), which had been transfected with the TEPC-15 VH and VL Ig genes, expresses surface Ig and secretes antibody that binds the hapten phosphorylcholine. We found that Ag (C polysaccharide and phosphorylcholine carrier Ag) and two different anti-idiotopic antibodies, in the absence of T cells, all inhibited the proliferation of the T15+ transfectant cell line. The anti-idiotopic antibodies, but not Ag, also inhibited the secretion of T15 Ig by this cell line, suggesting different functional roles for Ag vs anti-Id in the regulation of B cell inactivation. The inhibition of secretion and proliferation appears to be cell cycle phase related. In addition, mouse rIL-4 could override the inhibition of proliferation induced in these studies. These phenomena, demonstrating that binding of surface Ig can result in the transduction of negative growth signals to a B cell tumor, can be viewed as a manifestation of immunologic tolerance. These findings collectively demonstrate that Ag and anti-Id mediate different signals to B cells via interaction with the surface Ig. Because of the monoclonal nature of the T15 transfectant and the anti-idiotypic antibodies, this system can be used to investigate the underlying molecular reactions involved in the B cell response and induction of tolerance.

Animals↗
PubMed1988

Overgrowth, congenital hypotonia, nystagmus, strabismus, and mental retardation: variant of dominantly inherited Sotos sequence?

We report on 2 patients with macrocephaly, strabismus, esotropia, nystagmus, hypotonia, developmental delay, excessive size, unusual facial appearance, and improvement with age. Many of these abnormalities are present in Sotos sequence. The mothers of both patients share some characteristics with their children. These patients may represent an autosomal dominant form of Sotos sequence.

Female↗
PubMed1988

Structural basis of stimulatory anti-idiotypic antibodies.

In order to design and produce effective vaccines based upon the idiotype network hypothesis of Jerne, a thorough understanding of the biological and structural aspects underlying the stimulating activities of anti-idiotypic antibodies is needed. Here we determined the nucleotide sequence of the variable heavy and light chain regions of two monoclonal anti-idiotypic antibodies which induce different anti-phosphorylcholine responses. The nucleotide sequences of the variable domains of two monoclonal anti-TEPC 15 (T15) antibodies (F6-3 and 4C11) were determined by the primer extension and Maxam-Gilbert techniques. The nucleotide sequence data show that 4C11 and F6-3 have homologous VH segments and JH segments, but different D regions. The VH segments of both clones belongs to the J558 VH family. Most of the differences among the VH segments are located in CDR2. The VK segments of 4C11 and F6-3 are homologous to the VK gene group 4 and group 8, respectively. Comparison of the sequences of 4C11 and F6-3 with other published anti-idiotype antibodies shows that there is no preferential utilization of immunoglobulin genes. An analysis of the distribution of charged residues and hydropathic comparison studies were used to interpret the sequence of 4C11 in terms of the biological mimicry of antigenic stimulation.

Amino Acid Sequence↗
PubMed1988

Field airway management of the trauma patient: the efficacy of bag mask ventilation.

There is no consensus on what constitutes appropriate field airway management in the seriously injured semiconscious patient. The respiratory complications in a selected group of patients who were transported from the scene of an accident by a helicopter service whose policy was to perform endotracheal intubation on only deeply obtunded patients and manage others with bag mask ventilation are reported. Respiratory compromise was defined as follows: partial pressure of oxygen less than 65 torr on initial hospital arterial blood gases, partial pressure of carbon dioxide greater than 45 torr on initial hospital arterial blood gases, or radiographic and clinical evidence of aspiration pneumonitis within 5 days of admission to the hospital. From a total of 116 patients transported from the scene of an accident during the period of this investigation, there were 42 patients with Trauma Scores between 4 and 14 whose records were studied in detail. Ten of these patients ha adequate perfusion and abnormal arterial blood gases after arrival at the receiving hospital. Five patients might have benefited from endotracheal intubation in the field, but there were no preventable deaths. Neurologic status of the patient appeared to be more useful than respiratory status in predicting respiratory compromise.

Aircraft↗
PubMed1988

Duplex imaging of in situ saphenous vein bypass grafts and late failure reduction.

Duplex ultrasonic scanning was applied prospectively to 20 consecutive cases of in situ saphenous vein infrainguinal bypass 1, 3, 6, and 12 months postoperatively. All 20 (100 percent) and 17 of 19 (90 percent) of the proximal and distal anastomoses, respectively, could be imaged satisfactorily. Graft velocity ranged from 30 to 100 cm/s. Of three grafts with low velocity, one had impending graft failure and two had inherently low velocity but remained patent. Five defects in three grafts were detected. In three cases, intervention prevented graft failure. The primary patency rate was 80 percent, but was improved to 95 percent as a result of graft surveillance and simple revisions. Duplex scanning is a superior method for postoperative in situ saphenous vein bypass surveillance. We recommend that patients be studied 1 month postoperatively and every 3 to 6 months thereafter.

Adult↗
PubMed1988

Schistosoma mansoni: evidence that eosinophils and/or macrophages contribute to skin-phase challenge attrition in vaccinated CBA/Ca mice.

Naive CBA mice and mice vaccinated 4 weeks previously with gamma-irradiated cercariae were challenged percutaneously with normal cercariae and the skin site of challenge removed at various times to provide samples for histological examination. Neutrophil abscesses surrounding schistosomula as well as cast cercarial tails were identified at the skin surface in both naive/challenged and vaccinated/challenged mice. The dermis in both groups of animals became infiltrated with mononuclear cells and granulocytes. Neutrophils were the predominant granulocyte in naive/challenged skin but eosinophils replaced neutrophils by 48 h post-challenge in skin from vaccinated mice. Schistosomula with adherent mononuclear cells and granulocytes were identified preferentially in the dermis of vaccinated mice; such larvae frequently exhibited subtegumental vacuolation. A further major characteristic of vaccinated/challenged skin was the formation, from 18 h, of extensive subdermal inflammatory foci, consisting of up to 50% mononuclear cells and 50% eosinophils. These foci invariably surrounded one or more larval parasites which were seen by both optical and scanning electron microscopy to have a morphology typical of lung stage rather than skin stage schistosomula. Dead, infiltrated parasites were also recognized within the subdermal foci. Our data support the view that vaccine immunity in this mouse model is mediated primarily in the skin and indicate that challenge attrition involves immobilization and killing of larval parasites by effector cells within subdermal inflammatory foci.

Animals↗