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Biomedical subjects

R E Ward

Publications and source records attributed to R E Ward.

At least 73 records · Page 4Linked to original sources
PubMed1988

Biological mimicry of antigenic stimulation: analysis of the in vivo antibody responses induced by monoclonal anti-idiotypic antibodies.

In this study, the induction of protective antibodies against a bacterial pathogen in mice was used as a model for idiotype vaccine development. The antibody responses induced in different strains of mice by the hapten phosphorylcholine (PC) coupled to ovalbumin, PC-OVA, were compared with the responses induced by carrier conjugates of two different anti-idiotopic antibodies. One anti-idiotope, 4C11, exhibits the characteristics of an internal image of phosphorylcholine, and therefore is classified as an Ab2 beta; the other, F6, does not mimic antigen, and therefore is classified as an Ab2 alpha. The analysis of the temporal kinetics of the IgM and IgG1 anti-PC responses induced by nominal and idiotope antigens revealed dynamic responses characterized by changes in the quality and quantity of the antibody populations during the course of the immune response. All three antigens could stimulate antibodies that were PC-specific and T15 idiotope-positive in BALB/c and A/St mice. The highest titre of T15+ anti-PC antibodies was achieved with an immunization protocol which involved priming with Ab2 alpha followed by challenge with PC-OVA. Antibodies specific for the extended hapten, diazophenylphosphorylcholine, and hapten-carrier bridge determinants were being stimulated late in the responses to PC-OVA. BALB-c, A/St and CBA/N (Xid) mice all produced, late in the response to Ab2 alpha, high T15+ antibody titres which do not bind PC. The induction of T15+, non-PC binding, antibody suggests that T15 is a regulatory idiotope, expressed on antibodies having differing antigenic specificities. With regard to vaccine development, these results support the contention that effective induction of antibodies does not depend on stimulating a unique idiotope but can be achieved by anti-idiotypes reacting with different idiotopes. In addition, these results suggest that the combined use of idiotope and nominal antigens in an immunization protocol may provide the maximal protective immunity.

Animals↗
PubMed1987

Idiotope vaccine against Streptococcus pneumoniae. A precursor study.

An analysis of nominal vs idiotope antigen-induced B cell precursors was performed in A/St mice. With the use of the splenic fragment culture system, the quantity and quality of B cell precursors responding to two anti-idiotope carrier antigens (4C11 hemocyanin and F6 hemocyanin) and nominal antigen (phosphorylcholine-hemocyanin) were compared. In addition, the effect of priming with anti-idiotope-carrier antigens on B cell precursors responding to phosphorylcholine-hemocyanin was determined. We found that one anti-idiotope-carrier antigen, 4C11-hemocyanin, and phosphorylcholine-hemocyanin stimulated similar subpopulations of primary B cells. However, the B cell population stimulated by F6-hemocyanin, the other anti-idiotype complex, was distinct. Furthermore, priming with certain idiotope antigens can direct the phosphorylcholine-hemocyanin response into the expression of idiotypes that may be the most effective in protective immunity. Our results provide essential information for the rational design of idiotype vaccines by clarifying the dynamic relationship of the B cell precursor repertoire with the in vivo antibody response in the response to nominal and idiotope antigens.

Animals↗
PubMed1987

A syndrome of microcephaly, eye anomalies, short stature, and mental deficiency.

We have studied a mother and son with a previously apparently undescribed syndrome of microcephaly, eye defects, small ears, mild mental deficiency, and short stature. The syndrome appears to be an autosomal or X-linked dominant trait. The cat eye syndrome, blepharophimosis or Kohn-Romano syndrome, Rieger syndrome, and other disorders are discussed in relationship to this entity.

Abnormalities, Multiple↗
PubMed1987

Anthropometric analysis of the face in hypohidrotic ectodermal dysplasia: a family study.

Sixteen individuals with hypohidrotic ectodermal dysplasia (HED) were compared to normal standards as well as to 16 unaffected family members by using a series of 20 anthropometric measurements of the head and face. Individuals with HED were generally smaller than normal controls or their unaffected relatives. However, this size reduction was not uniform. Instead, it was most evident in the anterior-posterior dimensions of the lower two-thirds of the face, in facial height, and in the size of the ears, nose, and mouth. A stepwise discriminant function analysis indicated that a function constructed from four variables (depth of the lower face, width of the nose, mandibular arc, and total facial height) could accurately classify 96.7% of the 32 individuals in the combined sample of affected and unaffected individuals. These findings demonstrated that the face of individuals with HED is unique and can be useful in its diagnosis. Additional studies are needed to determine if similar-though-less-pronounced facial abnormalities can be used to detect minimally affected gene carriers of this presumably X-linked condition.

Adolescent↗
PubMed1987

Trauma Score change during transport: is it predictive of mortality?

The Trauma Score, a physiologic measure of injury severity, has been used to evaluate prehospital care by comparing the score before with the score after patient transport. To assess the value of the Trauma Score when used in this way, we compared the change in Trauma Score (TS change) during transport to eventual mortality in a group of injured patients. Patients transported by helicopter to the base hospital during a 22-month period had scores obtained on arrival of the flight crew (TS initial) and again on arrival at the emergency department (TS after transport). Stepwise logistic regression was used to test the predictive power for mortality of TS initial, TS after transport, and TS change. Of 387 patients transferred during the study period, 376 patients had complete information and were included in the analysis. Approximately 75% of patients had no TS change. The best predictor of mortality was TS after transport (F = 80.94, P less than .01). When TS after transport was removed as an explanatory variable, TS initial was found to have significant predictive power for mortality (F = 76.98, P less than .01), with TS change adding significantly to predictive power (F = 15.02, P less than .01). We conclude that because TS change is predictive of survival, it is potentially useful as an outcome measure to evaluate the impact of treatment during transport.

Adult↗
PubMed1987

Familial t(8;15)(p23.3;q22.3): report of two cases with dup(15) (q22.3----qter).

Two affected first cousins with duplication of 15(q22.3----qter) are reported. This resulted from a familial t(8;15)(p23.3;q22.3) translocation. The findings in these patients are compared with each other and with six other published cases. Anthropometric and dermatoglyphic findings are summarised.

Abnormalities, Multiple↗
PubMed1987

Tc-NGA imaging in liver transplantation: preclinical studies.

Tc-99m galactosyl-neoglycoalbumin (Tc-NGA) is a new liver-imaging agent which binds to hepatic binding protein (an hepatocyte-specific membrane receptor). This study evaluated the sensitivity of Tc-NGA kinetics and imaging anatomy to pathologic states that are encountered after liver transplantation. Studies were performed in adolescent pigs under control conditions (18 studies), and after orthotopic liver transplantation (nine studies), common bile duct ligation (three studies), hepatic artery ligation (one study), and hepatic resection (two studies). Anatomic and kinetic data were analyzed. Excellent liver images and minimal kinetic changes were noted after common bile duct ligation. Marked imaging defects and major kinetic alterations were observed after hepatic artery ligation and in the presence of preservation injury. Marked depression in hepatic Tc-NGA uptake was observed during acute rejection. Minor alterations in Tc-NGA kinetics were noted after a 25% hepatectomy. These studies indicate that minimal changes in Tc-NGA uptake occur after common bile duct ligation; Tc-NGA uptake is markedly sensitive to hepatic ischemia; decreased Tc-NGA uptake occurs during acute rejection; and hepatic infarcts are demonstrated promptly after preservation injury. Thus Tc-NGA imaging provides a novel means of evaluating hepatic ischemia, hepatic preservation, and hepatic allograft rejection. Tc-NGA imaging may also provide a means of evaluating hepatic regeneration and hepatocyte retrodifferentiation during regeneration.

Albumins↗
PubMed1987

Orthotopic liver transplantation in patients with cystic fibrosis.

An 11-year-old boy who had cystic fibrosis underwent an orthotopic liver transplantation. His immediate postoperative course was not unusually complicated when compared with other liver transplant recipients. Transplantation did not correct abnormalities in the sweat test or the respiratory disease. Cholestasis due to obstruction of the recipient duct with tenacious bile was cleared by instilling N-acetylcysteine into the duct. On the 48th day after the transplantation, he died of an intraventricular and intracerebral hemorrhage caused by an Aspergillus brain abscess. We conclude that certain patients with cystic fibrosis may be appropriate candidates for liver transplantation, but their pre- and post-operative management may need to differ from other liver transplant recipients.

Aspergillosis↗
PubMed1986

Idiotope antigens (Ab2 alpha and Ab2 beta) can induce in vitro B cell proliferation and antibody production.

We previously showed that immunization of various strains of mice with three types of antigen--PC-Hy (nominal antigen), F6-Hy (Ab2 alpha-Hy, and 4C11-Hy (Ab2 beta-Hy)--induces a differential PC-specific, T15-Id+ antibody response. In this report, the in vitro phosphorylcholine (PC)-specific B cell responses induced by these three antigens were studied. A hemocyanin-specific long-term T helper cell line was used to provide help for primary and secondary in vitro T cell-dependent B cell responses. At low doses (0.005 to 0.5 micrograms/ml) of antigen, a significant increase in the proliferation of PC-OVA-primed BALB/c B cells was observed with Ab2-Hy or PC-Hy conjugate, but not unconjugate, antigens. Similar low doses of antigen could stimulate naive B cells to secrete IgM and stimulate PC-OVA- or 4C11-Hy-primed B cells to secret IgM and IgG1 anti-PC antibodies. The percentage of T15-Id of the PC-specific antibodies produced in the in vitro T-B culture was found to be less dominant than that produced by in vivo immunization, suggesting that certain regulatory mechanisms occur in the in vivo environment that may help to maintain the T15-Id dominance. Taken together, our in vivo and in vitro results indicate that idiotope antigens can function like nominal antigens to induce antigen-specific B cell responses. The mechanisms of thymic-dependent B cell activation induced by idiotope and nominal antigen are similar in that the T-B interaction is MHC-restricted and requires cognate recognition.

Animals↗
PubMed1986

Parent to child transmission of the thrombocytopenia absent radius (TAR) syndrome.

We report on cases of the thrombocytopenia absent radius syndrome (TAR) in a family with the first documented occurrence of parent-to-child transmission. At least three other families have been reported in which TAR has been transmitted across generations. The pattern of transmission in these cases is not consistent with the simple autosomal recessive mode of inheritance which has been proposed. TAR syndrome may be a genetically heterogeneous disorder of the result of one of a group of related alleles. Given the increasing evidence for genetic and causal heterogeneity in TAR together with its similarity to conditions such as Holt-Oram, WT Limb-Blood and SC-Roberts Phocomelia syndromes it may be reasonable to view TAR as a developmental field defect rather than a genetic syndrome. Genetic counseling of affected individuals and their families should be modified to reflect the possibility of a recurrence risk as high as 50%.

Adult↗
PubMed1986

Monitoring of ionized calcium during human hepatic transplantation. Critical values and their relevance to cardiac and hemodynamic management.

During human hepatic transplantation, ionized calcium (ICa) measured in whole blood with an ion-selective electrode varied greatly from ICa predicted from total calcium (TCa), protein, albumin, and pH, by means of recently published nomograms. Measurement of ICa was necessary because the interaction of citrate in transfused blood and calcium chloride (administered to offset citrate binding) caused large variations in TCa. During hepatic transplantation, ICa and electrolyte measurements were obtained at approximately 15-minute intervals or more frequently if indicated by changing cardiac status. In one patient, hemodynamic instability was accompanied by a large decrease in ICa, which then was followed by cardiac arrest aggravated by myocardial depression from inadequate ICa. Cardiovascular phenomena associated with ionized hypocalcemia suggest that the critical value for ICa should be no more than 0.4 mmol/L (1.6 mg/dL) below the reference range mean. The authors propose critical limits for ICa and discuss their significance in clinical management of tetany, hypotension, arrythmias, and cardiac arrest.

Adolescent↗
PubMed1986

Rational design and application of idiotope vaccines.

Current emphasis on risk factors associated with established vaccines and pressing needs for vaccines against certain viral transmitted diseases have stimulated the search for new conceptual and practical approaches to vaccine production. Among these developments, the idiotope vaccine method has produced promising results. In this review the basic and conceptual principles for idiotype vaccine design are discussed. A novel approach for identifying idiotopic structures in the three dimensional structure of internal idiotope antigens is developed. The method is based on the relationship of the immune response with the evolutionary variation and diversity of the immunoglobulin family. Idiotopic structures are found in specialized topographic regions on the surface of the immunoglobulin molecule. The knowledge of these idiotope domains will facilitate the synthesis of idiotope expressing peptides and the computer modeling of the three dimensional structure of internal idiotope antigens. Finally, the existing evidence for successful application of the idiotope vaccine method is summarized and new disease groups are identified which could benefit from the development of idiotope vaccines.

Autoimmune Diseases↗
PubMed1986

Anesthetic, preoperative and postoperative considerations for liver transplantation in swine.

Perioperative care and anesthetic management of donor and recipient animals are crucial factors in studies involving experimental liver transplantation in the pig. Prevention of unacceptably high morbidity and mortality in the transplant recipients requires meticulous attention to anesthesia, preoperative and postoperative care. Liver transplant surgeries were performed using 15 pairs of pigs. Six of the transplant recipients were anesthetized with halothane plus 50% nitrous oxide (N2O) and oxygen (O2), and nine with isoflurane plus 50% N2O in O2. Arterial blood pressure, total anesthetic time, time of interruption of vena cava blood flow, and fluids administered, as well as length of survival were among the parameters measured and compared for the two groups. No deaths were attributed to either anesthetic technique. However, the isoflurane group had slightly higher blood pressure intraoperatively, better long range survival, and relatively rapid recoveries when compared to the halothane group. Because of these findings and the reported low rate of isoflurane metabolism and low resultant potential for formation of toxic metabolites when compared to halothane metabolism, we have elected to use the isoflurane-50% N2O regimen for this procedure.

Anesthesia↗
PubMed1986

Amatoxin poisoning in northern California, 1982-1983.

Twenty-two patients who ate mushrooms containing hepatotoxic amatoxins were treated during the fall and winter seasons of 1982 and 1983. All patients were treated with intensive supportive care and repeated oral doses of activated charcoal. In two patients fulminant hepatic failure developed and they died. One patient in whom encephalopathy developed had an orthotopic liver transplant and survived. Liver biopsy specimens obtained from five patients during the acute illness showed centrilobular hemorrhagic necrosis. The hepatic histopathology in a biopsy specimen from a 5-year-old boy eight weeks after mushrooms were eaten showed bands of fibrosis and islands of hepatocytes suggestive of early cirrhosis. Radioimmunoassay for amanitins, done on the serum from all patients, detected the toxins in only three, probably because most of the specimens were obtained 24 hours or more after the ingestion. This series, with a mortality rate of 9%, illustrates the outcome in patients who receive intensive supportive care and provides a background on which success of specific treatments should be judged.

Adolescent↗