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Biomedical subjects

B S Graham

Publications and source records attributed to B S Graham.

At least 109 records · Page 6Linked to original sources

Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice.

The role of CD4+ and CD8+ T lymphocytes in terminating respiratory syncytial virus (RSV) replication, causing disease, and protecting from reinfection was investigated using a BALB/c mouse model in which CD4+ or CD8+ lymphocytes or both were depleted by injections of Mab directed against the respective mouse lymphocyte determinants. Kinetics of RSV replication, illness, and pathology were assessed after primary infection and rechallenge. Both CD4+ and CD8+ lymphocyte subsets were involved in terminating RSV replication after primary infection. When both T lymphocyte subsets were depleted RSV replication was markedly prolonged, yet no illness was evident, suggesting that host immune response rather than viral cytocidal effect was the primary determinant of disease in mice. Both CD4+ and CD8+ lymphocytes contributed to illness, although CD8+ lymphocytes appeared to play the dominant role in this particular system. Analysis of histological responses suggested that CD4+ lymphocytes were required for the appearance of peribronchovascular lymphocytic aggregates seen in normal mice after rechallenge, and that the presence of alveolar lymphocytes was correlated with illness. It is postulated that antibody is an illness-sparing mechanism for protecting mice from RSV infection, and that T lymphocytes are an important determinant of illness. Further delineation of RSV-induced immunopathogenesis in primary infection and reinfection will provide important information for the development of vaccine strategies.

Animals↗

An in vivo and in vitro study of the loss of plasticizer from soft polymer-gel materials.

Polymer-gel materials used as short-term denture soft linings are blended with plasticizers to lower the glass transition temperature (Tg). A lower Tg allows for greater polymer chain mobility, thus producing a more flexible material. The present work evaluated the loss of plasticizers due to leaching both in vivo and in vitro. Two commercial denture soft-lining materials (A and B) were tested. These were both poly(ethyl methacrylate) polymers, blended with alcohol and phthalate esters. A clinical study was conducted in which patients wore, sequentially, dentures bearing (on separate occasions) each of the two soft-polymer lining materials. The two materials A and B were randomly assigned for each of ten patients and were worn for 14 and 30 days, respectively. With one exception, patients wore dentures with both lining materials, for a total of 19 clinical evaluations. The plasticizer loss occurring during the clinical trial was determined by GC analysis from the initial and terminal day sampling of plasticizer content of the soft polymer-gel materials. The results of this analysis were compared with results obtained from an in vitro leachability study by use of sink conditions in water at 37 degrees C for the same two commercial soft polymers conducted over the same time periods of 14 and 30 days. The results indicated that a higher loss of plasticizer occurred in vivo, compared with the in vitro tests for 17 of the 19 clinical evaluations. The average plasticizer lost in vivo from material A at 14 days was 122 +/- 58 mg/g, and for material B at 30 days it was 33 +/- 27 mg/g.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗

Growth of human cell lines in BALB/c mice.

A method of immunodepletion that allows the growth of xenogeneic cell lines in mice is described. Treatment of adult BALB/c mice with sublethal irradiation (400 total body rads) and CD4+ lymphocyte depletion renders them tolerant to the growth of human lymphocytic (CEM), monocytic (U937), and epithelial (HEp-2) cell lines. The system has also been used to generate ascites from rat hybridomas. The methodology is technically easy, inexpensive, and expedient and should have multiple uses in biomedical research including mouse modeling of human viral infections and investigation of transplant rejection.

Animals↗

Clinical compliance of two resilient denture liners.

Although intra-oral-setting resilient denture liners have been used for 30 years to treat the severely resorbed residual ridges of elderly patients, their clinical physical properties are not well understood. The effect of clinical usage on the compliance (compressibility, flexibility) of two intra-oral-setting resilient denture liners was measured in 10 patients, for up to 30 days. The clinical compliance of Material B (Coe-Comfort) was found to be significantly greater than Material A (Veltec) for up to 14 days. At 24 h both materials had significant compliance reductions from the original 1 h measurement. These compliance reductions continued throughout the testing period. For up to 14 days of clinical usage there were no significant differences between the compliance reductions of the two materials. The study suggests that (i) Material B would provide more effective tissue conditioning of abused residual ridge mucosa than Material A; and (ii) a functional impression made with these materials should be left in the mouth for at least 24 h before the cast is poured.

Acrylic Resins↗

Antifusion activity in sera from persons infected with human immunodeficiency virus type 1.

Cell-to-cell fusion plays an important role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1) infections. An assay to measure the antifusion activity of serum has been developed by using the fusion event that occurs between H9 cells chronically infected with HIV-1 (H9IIIB) and fusion-susceptible MT-2 cells. The endpoint is determined by measuring neutral red uptake in cells after syncytium formation is allowed to occur in the presence of various serum dilutions. The assessment of antifusion activity in serum by neutral red uptake has been shown to correlate with syncytium reduction as determined by direct counting. The optimal number and ratio of cells in the suspension for efficiency and speed of the assay have been determined. With this assay it was shown that 50% of 36 serum specimens capable of neutralizing cell-free virions failed to inhibit syncytium formation. The assay can thus measure a distinct activity in HIV-1-immune human sera which is a subset of neutralization activity. Because of the potential role of this activity in the rate of disease progression and protective immune responses, the antifusion assay will be an important tool for the investigation of disease pathogenesis and for acquired immunodeficiency syndrome vaccine development. The assay can also be applied to the investigation of the pathogenesis of the fusion event at the cellular level. The ability to use absorbance measurements rather than syncytium counts as the endpoint facilitates direct computer-assisted data analysis, which expedites the performance of the assay.

Cell Fusion↗

Development of an AIDS vaccine. Biological and ethical challenges.

The biologic, ethical, and social obstacles in AIDS vaccine development are explored. Current understanding of the immunodeterminants of HIV-1 pathogenesis is reviewed and ideal biological properties for an AIDS vaccine are proposed. Options for clinical trial design, criteria for entry into clinical trials, and provision for care of volunteers who experience vaccine-associated adversity are discussed.

Acquired Immunodeficiency Syndrome↗

Mycobacterium chelonae: a cause of nodular skin lesions with a proclivity for renal transplant recipients.

PURPOSE: Infections due to Mycobacterium chelonae are uncommon. Several renal transplant recipients at our medical center have developed M. chelonae infections during the past several years, so we decided to review our recent experience with M. chelonae infections. PATIENTS AND METHODS: The clinical microbiology laboratory records of four Vanderbilt University Affiliated Hospitals were reviewed. Ten patients with M. chelonae tissue or blood infections were identified between 1982 and July 1988. RESULTS: All infections involved the skin and subcutaneous tissue. Three infections developed at the sites of medical injections. The remaining seven infections occurred in renal transplant recipients and produced a clinically distinctive syndrome. All were indolent tender nodular lesions on the extremities, usually the lower legs. Systemic symptoms were absent, and white blood cell counts were within normal limits. Diagnosis required tissue biopsy and cultures that were incubated for a month. Therapy consisted of surgical excision combined with long-term antibiotics. Even so, some patients had a chronic, relapsing course. CONCLUSION: Although other diagnoses must be considered, the presumptive diagnosis of M. chelonae infection is suggested by the appearance of nodular erythematous lesions on the legs of a renal transplant recipient.

Adult↗

Clinical implications of resilient denture lining material research. Part I: Flexibility and elasticity.

The clinical use of resilient denture liners is based on their flexibility and elasticity. The nine commercial resilient denture liners measured were less flexible during and after simulated chewing and clenching test sequences. The elasticity of the intraoral-cure liners reached maximal values at 24 hours. Although interpretations require caution, the results imply that the dentist should (1) use maximum liner thickness in the denture base when conditioning abused supporting tissues because of the material's tendency to stiffen under function, and (2) leave a functional impression in the mouth for at least 24 hours before pouring the cast.

Chemical Phenomena↗

Primary respiratory syncytial virus infection in mice.

A mouse model of respiratory syncytial virus (RSV) infection is described. A high-titered, large-volume inoculum results in replication of RSV to a high titer in lungs of BALB/c mice. Mice older than 15 weeks of age are more susceptible to RSV infection. Titers up to 10(6.9) plaque-forming units (pfu)/gram lung can be attained in 32-week-old mice. Older mice experience a clinical illness manifested by ruffled fur, reduced activity, and weight loss. Lung histology of older mice infected with RSV shows bronchiolitis and increased number of lymphocytes and macrophages in alveolar spaces compared with that of mice less than 8 weeks old. This model will serve as the basis for investigating immunodeterminants of recovery and protection from RSV infection.

Age Factors↗

Strain-specific serum antibody responses in infants undergoing primary infection with respiratory syncytial virus.

We sought to characterize the human respiratory syncytial virus (RSV) subgroup-specific antibody response to primary infection with RSV. RSV isolates from 43 infants and young children were typed as either subgroup A (Long strain-like) or B (18537 strain-like) based on reactivity with monoclonal antibodies. Acute-phase or preinfection and convalescent-phase sera were collected from the 43 subjects and tested in an enzyme-linked immunosorbent assay using purified F and G glycoproteins from RSV subgroups A and B and by neutralization assay against both subgroups of RSV. Twenty-six individuals had rises in titer of antibody to F glycoprotein, 27 to G glycoprotein, and 28 had rises in titer of neutralizing antibody. The antibody responses to homologous and heterologous F glycoproteins were not significantly different. In contrast, homologous vs. heterologous antibody responses to G glycoprotein were significantly different, with 7.3% relatedness between the G glycoproteins of subgroups A and B. Analysis of neutralizing antibody responses revealed 31% relatedness.

Antibodies, Monoclonal↗

Nonexertional heatstroke. Physiologic management and cooling in 14 patients.

Fourteen patients with nonexertional heatstroke were evaluated in a general hospital during the summer of 1980. They were managed according to a prospectively devised protocol designed to effect heat dissipation primarily via convection and evaporation rather than by conduction. The time from entry into the emergency room to the first recorded rectal temperature of less than 103 degrees F (39.4 degrees C) ranged from 34 to 89 minutes (median, 60 minutes). Only one patient died; none had residual neurologic deficits. The use of these methods can result in a low incidence of permanent neurologic impairment and a low fatality rate.

Adult↗

Clostridial infection of renal cell carcinoma.

We report a case of a large gas-filled clostridial abscess in a previously unrecognized renal cell carcinoma. Neoplastic tissue has a nonhomogeneous blood supply, creating areas of hypoxia and reduced glucose concentrations, which lead to tumor necrosis and an environment conducive to the growth of anaerobic organisms. Anaerobic infection should be considered in any patient with carcinoma and fever. Conversely, abscess transformation of a tumor can be the explanation for what otherwise seems to be the spontaneous development of a parenchymal abscess.

Abscess↗

Endocarditis and infections of intravascular devices due to Eikenella corrodens.

Eikenella corrodens, a microaerophilic gram-negative rod, is a normal inhabitant of human mucosal surfaces. Infections involving Eikenella have been reported with increasing frequency during the past 10 years. Despite a demonstrated ability to invade the blood stream, Eikenella has rarely been implicated in endocarditis or other vascular space infections. Two patients are reported with prolonged illness due to infection of peripheral vascular prostheses with E. corrodens and prior reports of Eikenella vascular space infections are reviewed. When Eikenella is the sole infecting organism, vascular space infections tend to be indolent. However, removal of vascular prostheses may be required for cure.

Adult↗

Serum and nasal-wash immunoglobulin G and A antibody response of infants and children to respiratory syncytial virus F and G glycoproteins following primary infection.

An enzyme-linked immunosorbent assay (ELISA) with immunoaffinity-purified fusion (F) or attachment (G) glycoprotein was used to measure the serum and secretory immune responses of 18 infants and children, 4 to 21 months of age, who underwent primary infection with respiratory syncytial virus (RSV). Most of the 10 older individuals (9 to 21 months of age) developed moderate levels of serum and nasal-wash immunoglobin A (IgA) and IgG F and G antibodies. These individuals developed a moderate level of serum or nasal-wash antibodies that neutralized virus infectivity. One of the eight younger individuals (4 to 8 months of age) failed to develop an F antibody response, while three failed to develop a G antibody response. The most notable difference in the responses of the two age groups involved the titer in convalescent sera of G, F, and neutralizing antibodies which were 8- to 10-fold lower in younger individuals. Most of the younger infants failed to develop a rise in serum or nasal-wash neutralizing antibody. It is possible that the presence of maternally derived antibody in the younger infants suppressed the immune response to RSV infection, and that this accounted, in part, for the low level of postinfection antibody titer in this group. This low level and the irregular response of the infants less than 8 months of age may contribute to the severity of their initial infection and may also be responsible, in part, for their failure to develop effective resistance to subsequent reinfection by RSV.

Antibodies, Viral↗

Serum immunoglobulin G antibody subclass responses to respiratory syncytial virus F and G glycoproteins after primary infection.

Because the immunoglobulin G (IgG) response to carbohydrate antigens is typically from the IgG2 subclass and the IgG response to protein antigens is typically from the IgG1 and sometimes the IgG3 subclass, two respiratory syncytial virus glycoproteins, F and G, which differ substantially in the amount of glycosylation, were used as antigens in an enzyme-linked immunosorbent assay to determine IgG subclass responses in 20 infants and young children with naturally acquired respiratory syncytial virus infection. Both glycoproteins elicited primarily IgG1 and IgG3 responses, indicating that the protein moieties of the glycoproteins may be immunodominant in this age group.

Antigens, Viral↗

Effect of age and preexisting antibody on serum antibody response of infants and children to the F and G glycoproteins during respiratory syncytial virus infection.

The serum antibody response of 50 infants and children infected with respiratory syncytial virus (RSV) was determined by a glycoprotein-specific enzyme-linked immunosorbent assay, and the effects of age and preexisting antibody titer at the time of RSV infection on response to the G and F glycoproteins of RSV were examined. The immune response to the G and F glycoproteins was assessed with anti-human immunoglobulin A to permit measurement of the response of young infants in the presence of maternally derived immunoglobulin G. The findings suggested that age primarily affects the response to the F glycoprotein and that preexisting antibody titer affects the response to the G glycoprotein.

Aging↗