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Biomedical subjects

P Graves

Publications and source records attributed to P Graves.

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

Human immune response directed against Plasmodium falciparum heat shock-related proteins.

Heat shock-related stress proteins present in all eucaryotes and procaryotes have been shown to be immune targets in a broad range of infections. We have analyzed sera from people exposed primarily to Plasmodium falciparum for specific antibodies against two heat shock-related proteins (proteins similar to the heat shock protein with a molecular weight of 75,000 [Pfhsp] and a glucose-regulated protein with a molecular weight of 72,000 [Pfgrp]). In an immunoprecipitation analysis with metabolically labeled parasites and synthetic peptides in an enzyme-linked immunosorbent assay, specific antibodies against Pfhsp and Pfgrp were detected in the sera of these individuals. Sera from people exposed to a different human malarial parasite, Plasmodium vivax, did not react with the peptides in an enzyme-linked immunosorbent assay. Southern blot analysis with DNA isolated from P. falciparum from different geographical locations showed a conservation of genes for these stress proteins; thus, they are likely to be immune targets in various endemic areas. Lymphocytes from two tested immune donors responded in proliferation assays to purified Pfhsp and Pfgrp and purified recombinant proteins. However, a similar response was also seen in lymphocytes from nonimmune individuals and has raised questions pertaining to a generalized responsiveness of lymphocytes to some common determinants present in heat shock-related proteins in various pathogens.

Animals↗
PubMed1989

Effectiveness of influenza vaccine when given during an outbreak of influenza A/H3N2 in a nursing home.

An explosive outbreak of influenza A/H3N2 began in a nursing home in the Denver area early in November, 1987. Residents had not been vaccinated at that time. Vaccine was administered on November 11th. Two weeks after the vaccine was given, the attack rate differed between the vaccinated and unvaccinated individuals. There were 40 cases of influenza among the 98 elderly residents, 12 cases of pneumonia, and seven deaths. Vaccine efficacy two weeks after it was given was estimated to be 65.4% in preventing clinical illness. There were no cases of pneumonia and no deaths among people who were vaccinated more than two weeks before. The virus was identified as influenza A by complement fixation tests with convalescent sera from 16 individuals who had been ill. Many also had hemagglutination inhibition titers for A/Colorado/1/87, which were as high as titers for A/Leningrad/87. A/Colorado/1/87 closely resembled A/Sichuan/87.

Aged↗
PubMed1989

Differential cytokine regulation of MHC class II and thyroglobin mRNAs in rat thyroid cells.

We have previously demonstrated that recombinant gamma-interferon (gamma IF) inhibits thyroid cell proliferation in vitro. We now demonstrate differential regulation of thyroid cell genes by recombinant gamma IF, as evidenced by data obtained measuring thyroglobulin (Tg) mRNA and MHC class II alpha-chain mRNA transcripts. Using the rat thyroid cell clone 1B-6, derived from FRTL-5 cells, gamma IF markedly increases MHC class II (RT1.D) alpha-chain transcripts in proliferating cells. Simultaneously, Tg mRNA transcript levels are markedly inhibited, even in the presence of TSH and insulin-like growth factor I (as insulin), known stimulators of Tg mRNA. Similar data were obtained for both FRTL-5 and FRTL parent cell lines. Furthermore, using probes to the 5' region of the rat Tg gene we recognized not just a 9.0-kilobase (kb) mRNA, but also an additional 1.1-kb message in all proliferating thyroid cell cultures, suggesting truncation or alternative splicing of the Tg mRNA. Both the 9.0- and 1.1-kb mRNAs were inhibited by gamma IF. These data add further complexity to the cytokine regulation of thyroid cell gene expression and advise caution in making the assumption that thyroid cells may be efficient thyroid antigen-presenting cells in thyroid autoimmune disease.

Animals↗
PubMed1988

Human autoimmune thyroid disease: cellular and molecular aspects.

We have reviewed the impact of cellular and molecular biology on our understanding of the immune system and thyroid autoimmune disease and presented the evidence that MHC, TCR and immunoglobulin genes are involved in susceptibility to such disease. At the level of the target thyroid epithelial cell, the identification of the genes for Tg and TPO (the microsomal antigen) using recombinant DNA techniques are evidence of dramatic progress. On the humoral side of the immune response, the investigation of restricted clonality is still hampered by the technical difficulties in obtaining immortal B cell lines producing thyroid antigen specific high affinity IgG antibodies, although the advent of tools to sequence the immunoglobulin V genes from small quantities of DNA will overcome this difficulty (e.g. by polymerase chain reactions). T cells have also begun to be characterized both phenotypically, thanks to the advent of ever better characterized monoclonal antibodies, and functionally at the clonal level, thanks to refinement of cell culture techniques. Future studies in this area will also need to focus on cell immortalization and maintenance of antigen-specific responses although, major strides in the direct sequencing of the TCR are taking place and investigation of T cell receptors in antigen-specific T cells should be feasible. MHC associations with thyroid autoimmune disease, as studied by analysis of RFLP patterns, have not significantly improved already established serological HLA associations and direct MHC gene sequencing will be required. Analysis of the organ-specific regulation of MHC class II gene expression has led to a better understanding of the functional role of MHC class II genes in thyroid autoimmune disease at the target cell level. Such studies have pointed out important local immune responses within the thyroid gland but have not yet provided the initiating factor or factors for human autoimmune thyroid disease in genetically susceptible individuals.

Antigens↗
PubMed1986

Factors influencing invasion of erythrocytes by Plasmodium falciparum parasites: the effects of an N-acetyl glucosamine neoglycoprotein and an anti-glycophorin A antibody.

When schizont-infected erythrocytes were incubated with N-acetyl glucosamine coupled to bovine serum albumin (GluNAc-BSA), the number of new ring forms which appeared several hours later was reduced and the number of abnormal and unruptured schizont-infected erythrocytes was increased compared with controls, indicating that GluNAc-BSA prevents invasion by a toxic effect on schizonts rather than by receptor blockade. Invasion of erythrocytes by Plasmodium falciparum was inhibited by a monoclonal antibody against glycophorin A, but inhibition also occurred with P. knowlesi, a parasite that is known to invade independently of glycophorin A. Inhibition of invasion with anti-glycophorin A is unlikely to be related to receptor blockade and is probably related to decreased deformability of the erythrocyte membrane caused by the binding of this antibody. Previous studies suggesting that GluNAc-BSA and anti-glycophorin A antibodies inhibit invasion by receptor blockade should be reevaluated. Erythrocytes deficient in glycophorin C and band 4.1 were also resistant to invasion by both P. falciparum and P. knowlesi.

Acetylglucosamine↗
PubMed1984

Effects of guanabenz in adolescent hypertension.

Fourteen adolescent patients, aged 12 to 21 years, with essential hypertension were treated on an open basis with guanabenz, a centrally acting antihypertensive agent. Guanabenz doses of 3-24 mg/day (0.08-0.20 mg/kg/day) given twice daily for 2 months effectively lowered mean supine blood pressure (p less than 0.05), standing blood pressure (p less than 0.01), and supine pulse rate (p less than 0.01). Body weight and standing pulse rate were unaffected. Adverse effects were mild, usually short lived, and did not interfere with therapy. No adverse effects were noted in laboratory test results or physical examinations. Baseline funduscopic photography revealed numerous but minor changes, including altered arteriovenous ratios and crossing changes. Prestudy echocardiograms revealed changes consistent with early hypertensive changes. Poststudy echocardiograms obtained in nine of the 14 subjects after 4-6 weeks of guanabenz therapy suggested that cardiac hypertrophy had regressed, but these changes did not reach statistical significance. These preliminary results suggest that guanabenz can be a safe and effective treatment for hypertensive children, that early hypertensive changes can be seen in the fundi and echocardiograms of mildly hypertensive adolescents, and that some echocardiographic changes may be reversed even after relatively short-term guanabenz therapy.

Adolescent↗
PubMed1979

Digoxin-quinidine interaction Pharmacokinetic evaluation.

Several recent reports have shown that plasma concentrations of digoxin increase when quinidine is administered along with digoxin; the present study was designed to explore the pharmacokinetics of this digoxin-quinidine interaction in six subjects. The elimination half-life of digoxin, although variable, did not change appreciably (42 vs. 44 hours) when quinidine was administered. Other pharmacokinetic values were substantially reduced in the presence of quinidine: total body clearance (from 3.08 to 1.96 ml per minute per kilogram), renal clearance (from 1.64 to 1.09 ml per minute per kilogram) and volume of distribution (from 10.87 to 7.35 liters per kilogram). The results may be explained by the displacement of digoxin from binding sites in tissue by quinidine, causing a rise in the plasma concentration of digoxin. The reduction in renal clearance of digoxin may result also from inhibition of renal secretion of digoxin by quinidine.

Digoxin↗
PubMed1978

Antigenic drift and efficacy of influenza virus vaccines, 1976--1977.

A unique opportunity occurred in February 1977 to assess the efficacy of an influenza virus vaccine given to military personnel in doses of 400 chick cell-agglutinating (CCA) units of A/Victoria/3/75, 400 CCA units of A/New Jersey/76, and 500 CCA units of B/Hong Kong/72 viruses. After cessation of all influenza virus vaccine administration in mid-December 1976, approximately 200 unvaccinated U.S. Air Force personnel arrived per week beginning February 1, 1977, at Lowry Air Force Base, Denver, Colorado. Arriving unvaccinated personnel were assigned to one of 12 units with previously vaccinated personnel. A sharp outbreak of influenza A occurred on the base during February that was due to an A/Texas/1/77-like virus, a variant of the A/Victoria/3/75 prototpye. Fifty-four cases of influenza A were documented in the student population on the base. During the two-week peak of the outbreak, attack rates were 10-fold higher in unvaccinated than in vaccinated students, and the overall estimate of vaccine efficacy was 80%. Thus, despite animal tests suggesting considerable antigenic drift, a vaccine containing influenza A/Victoria/3/75 virus provided good protection against the variant strain.

Adolescent↗
PubMed1977

Antibody response of young adults to experimental influenza A/New Jersey/76 virus vaccines.

In military personnel aged 17-25 years, only one of four experimental influenza A/New Jersey/76 virus vaccines produced a satisfactory hemagglutination-inhibiting (HAI) antibody response when a dose of 200 chick cell-agglutinating (CCA) units was used. A second injection of 400 CCA units of vaccine caused seroconversion in all persons. Although an early comparison of experimental split-product and whole-virus vaccines suggested that the former were relatively ineffective, a later comparison with different lots of the vaccines showed no difference between vaccines of these two types. The influenza A/NJ/76 virus vaccine evoked a high HAI antibody response to influenza A/PR/8/34 (H0N1) virus but not to H1N1 or H3N2 strains.

Antibodies, Viral↗
PubMed1977

Impaired serum antibody response to inactivated influenza A and B vaccine in renal transplant recipients.

Before and after vaccination with a commercial inactivated influenza vaccine containing A/Aichi/2/68 (H3N2) and B/Massachusetts/1/71 antigens, the serum hemagglutination inhibition antibody titers to homologous and heterologous strains of A and B influenza viruses were measured in 45 renal transplant patients and 66 healthy controls (62 for the B strains). At least a fourfold titer rise to the homologous A strain occurred in 14 of 45 transplant patients (31%) versus 37 of 66 controls (56%). Fourfold or greater heterologous A rises occurred in only 8 of 45 transplant patients (18%) compared with 40 of 60 controls (61%). In both the homologous and heterologous B responses, at least fourfold hemagglutination inhibition titer rises were seen in significantly fewer transplant patients than control subjects. In the transplant group, no correlation was observed between degree of antibody response and age, previous influenza vaccination, percentage of patients initially seronegative, time since transplantation, dose of immunosuppressive drugs, level of renal function, or nature of original renal disease.

Adolescent↗