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Biomedical subjects

E Johnson

Publications and source records attributed to E Johnson.

At least 163 records · Page 9Linked to original sources
PubMed1996

Specificity of binding of beta-glucoside activators of ryegrass (1-->3)-beta-glucan synthase and the synthesis of some potential photoaffinity activators.

Structure-activity relationships among glycoside activators of ryegrass (Lolium multiflorum) (1-->3)-beta-glucan synthase were investigated using a number of natural and synthetic glycosides, including some carrying photoaffinity functions. There is an absolute requirement for a beta-D-glycosyl moiety in the activator, both S- and N-glucosides are active, and the position of the glucosidic linkage in beta-glucose disaccharides has a significant effect on the affinity of binding. However, the binding requirement does not extend beyond a single beta-D-glucosyl residue, and beta-D-oligoglucosides are less effective than disaccharides. The nature of the aglycon has a major influence on the binding affinity. Hydrophobic aglycons lower the concentration required for half-maximal stimulation of the enzyme obtained from an Eadie-Hofstee plot of kinetic data (Ka) for activation, but charge aglycons increase Ka. Relative to methyl-beta-D-glucoside and cellobiose (Ka 1.1 mM), the most potent compounds tested were N-[4-(benzoyl)benzoyl]-beta-D-glucosylamine and 2'-[4-azidosalicylamino]ethyl-1-thio-beta-D-glucoside with K(a)s of approximately 30 microM. The latter also was tested for its potential to specifically label the beta-glucoside-binding site on the synthase, but under the conditions used the binding was found to be nonspecific.

Enzyme Activation↗
PubMed1996

Subtypes of incarcerated delinquents constructed via cluster analysis.

The MMPI and Jesness Inventory were used to construct groupings of juvenile delinquents homogeneous with respect to personality characteristics. Subjects were 191 incarcerated juvenile delinquents, aged 12 to 19. All participants had been adjudicated on one or more serious offenses. Five subtypes of delinquents were identified. They included an alienated, unsocialized group, an insecure-anxious group, a group reporting limited difficulties with peers but alienated from adults, a group with no apparent emotional disturbance, and a group with multiple elevations. Significant differences between clusters with regard to self-reported explosiveness, suicidality, gang activities, substance abuse, history of sexual abuse, and delusions and hallucinations were identified. Discriminant function analysis was then used to support the generalizability of the classification system to an independent sample. Eighty per cent of the second sample were accurately classified. The subtypes identified are compared to delinquent classification systems developed previously.

Adult↗
PubMed1996

Interleukin-1 alpha, interleukin 6 and tumor necrosis factor alpha increase the synthesis and expression of the functional alternative and terminal complement pathways by human umbilical vein endothelial cells in vitro.

The proinflammatory cytokines interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) modulate the synthesis of complement factors B and C3 by endothelial cells (EC), and are considered to play an important role in the development of sepsis. By using agarose beads activating the alternative pathway of complement, we wanted to study the net effect of these cytokines on EC synthesis of the alternative and terminal pathways, measured by binding of anti-C3c and anti-TCC (terminal complement complex) antibodies to beads kept with the EC. Addition of IL-1 alpha and TNF alpha at concentrations of 50 and 100 U/ml resulted in a significant increase in binding of these antibodies to co-incubated beads, most pronounced for anti-C3c. IL-6 from 50-200 U/ml resulted in a stronger (two to fourfold) binding for both antibodies compared to experiments with IL-1 alpha and TNF. However, increased concentrations of IL-1 alpha (200 U/ml) and IL-6 (400 U/ml) resulted in a strong reduction in binding of anti-C3c and anti-TCC antibodies to the co-cultured beads. This study indicates that proinflammatory cytokines upregulate the synthesis by EC of the functional alternative and terminal pathways of complement.

Cells, Cultured↗
PubMed1996

Simian immunodeficiency virus DNA vaccine trial in macaques.

An experimental vaccine consisting of five DNA plasmids expressing different combinations and forms of simian immunodeficiency virus-macaque (SIVmac) proteins has been evaluated for the ability to protect against a highly pathogenic uncloned SIVmac251 challenge. One vaccine plasmid encoded nonreplicating SIVmac239 virus particles. The other four plasmids encoded secreted forms of the envelope glycoproteins of two T-cell-tropic relatives (SIVmac239 and SIVmac251) and one monocyte/macrophage-tropic relative (SIVmac316) of the uncloned challenge virus. Rhesus macaques were inoculated with DNA at 1 and 3, 11 and 13, and 21 and 23 weeks. Four macaques were inoculated intravenously, intramuscularly, and by gene gun inoculations. Three received only gene gun inoculations. Two control monkeys were inoculated with control plasmids by all three routes of inoculation. Neutralizing antibody titers of 1:216 to 1:768 were present in all of the vaccinated monkeys after the second cluster of inoculations. These titers were transient, were not boosted by the third cluster of inoculations, and had fallen to 1:24 to 1:72 by the time of challenge. Cytotoxic T-cell activity for Env was also raised in all of the vaccinated animals. The temporal appearance of cytotoxic T cells was similar to that of antibody. However, while antibody responses fell with time, cytotoxic T-cell responses persisted. The SIVmac251 challenge was administered intravenously at 2 weeks following the last immunization. The DNA immunizations did not prevent infection or protect against CD4+ cell loss. Long-term chronic levels of infection were similar in the vaccinated and control animals, with 1 in 10,000 to 1 in 100,000 peripheral blood cells carrying infectious virus. However, viral loads were reduced to the chronic level over a shorter period of time in the vaccinated groups (6 weeks) than in the control group (12 weeks). Thus, the DNA vaccine raised both neutralizing antibody and cytotoxic T-lymphocyte responses and provided some attenuation of the acute phase of infection, but it did not prevent the loss of CD4+ cells.

Animals↗
PubMed1996

Evidence that replication of human neurotropic JC virus DNA in glial cells is regulated by the sequence-specific single-stranded DNA-binding protein Pur alpha.

Initiation of polyomavirus DNA replication in eukaryotic cells requires the participation of the viral early protein T antigen, cellular replication factors, and DNA polymerases. The human polyomavirus JC virus (JCV) is the etiologic agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy in immunocompromised individuals. This virus exhibits a narrow host range and a tissue specificity that restricts its replication to glial cells of the central nervous system. Restriction of viral DNA replication due to species specificity of the DNA polymerase, coupled with glial cell-specific transcription of the viral early promoter, is thought to account for the brain-specific replication of JCV. In this report we demonstrate that overexpression of Pur alpha, a protein which binds to single-stranded DNA in a sequence-specific manner, suppresses replication of JCV DNA in glial cells. Results from footprinting studies indicate that Pur alpha and T antigen share a common binding region spanning the single-stranded ori sequence of JCV. Further, T antigen was capable of stimulating the association of Pur alpha with the ori sequence in a band shift assay. Whereas no evidence for simultaneous binding of Pur alpha and T antigen to single-stranded DNA has been observed, results from coimmunoprecipitation and Western blot (immunoblot) analyses of proteins derived from cells producing JCV T antigen indicate a molecular association of JCV T antigen and Pur alpha. The binding of Pur alpha to the single-stranded ori sequence and its association with T antigen suggest that Pur alpha interferes with the activity of T antigen and/or other regulatory proteins to exert its negative effect on JCV DNA replication. The importance of these findings in the reactivation of JCV in the latently infected individual under immunosuppressed conditions is discussed.

Antigens, Viral↗
PubMed1996

Botulinum toxin therapy, immunologic resistance, and problems with available materials.

Botulinum toxin is a valuable technology for the treatment of regional movement disease. High-dose applications ( > 100 LD50 units per injection cycle) have been associated with sensitization that renders further therapeutic injections ineffective. The true incidence of sensitization is probably underestimated by the mouse bioassay. Other immunotypes of botulinum toxin have been effective in producing some therapeutic benefit; however, duration of action (botulinum toxin type F) and lower potencies may make these less attractive alternatives than botulinum type A. Increased specific activity botulinum toxin may be a method to reduce antigen exposure and mitigate against immunoresistance associated with dystonia therapy. Limiting the dose to < or = 100 LD50 units per injection cycle may limit this complication in the interim.

Botulinum Toxins↗
PubMed1996

DNA-confirmed Taenia solium cysticercosis in black bears (Ursus americanus) from California.

Three cases of cysticercosis in black bears (Ursus americanus) in three northern California counties between 1990 and 1994 have been identified as due to the tapeworm Taenia solium. Both morphologic characteristics as well as the presence of T. solium mitochondria cytochrome oxidase I gene sequences, as detected by the polymerase chain reaction, confirmed the diagnosis. The number and geographic separation of the cases suggests that infection of the bears was not due to a single contamination. Humans infected with the definitive stage of T. solium are the probable source of cysticercosis for bears, as well as other humans. This is the first confirmation of cysticercosis due to T. solium in a black bear in North America.

Animals↗
PubMed1996

Vulvar intraepithelial neoplasia and vulvar cancer.

Vulvar carcinoma is a rare cancer. It is more frequent among older women, but the incidence is increasing among younger women. The incidence of VIN may be rising in younger women as well. Different factors have been associated with an increased risk for vulvar cancer (HPV, age, smoking, education, diet, genital infections, infrequent pelvic examinations, socioeconomic status, immunosuppressive diseases); however, conclusive epidemiologic evidence is lacking. More studies with larger sample sizes are needed to understand more fully the role of these and other as yet unknown factors in the etiology of vulvar cancer. At present, studies of the molecular risk assessment for VIN and vulvar cancer focus mostly on HPV. The treatments for VIN are painful, and the disease has a high risk of recurrence. The treatments for vulvar cancers are morbid, even though radical vulvectomy is being replaced by the less morbid wide local excision and unilateral groin lymph node dissection. Therefore, VIN and vulvar cancer benefit from early detection, and their morbidity is decreased by early treatment. Screening should be performed by the primary care practitioner and should focus on women with HPV; women who smoke; and women who have other preinvasive disease of the cervix, vagina, or perianal area. Chemoprevention and an HPV vaccine may eventually be promising, but no studies have yet been performed. Patients should be educated about performing vulvar self-examination stopping smoking, being persistent about insisting on a biopsy if symptoms persist, and avoiding exposure to HPV.

Biomarkers, Tumor↗
PubMed1996

Vaginal intraepithelial neoplasia and vaginal cancer.

Vaginal cancer is infrequent, but the morbidity associated with treatment is high. Delays in diagnosis account for presentations in advanced stages. Screening is probably not warranted given the low incidence, but inspection of the vagina should be performed at the time of Pap smear screening. No molecular markers are currently promising. Chemoprevention with retinoids may be feasible.

Carcinoma in Situ↗
PubMed1996

Cervical intraepithelial neoplasia and cervical cancer.

Cervical cancer remains an important health problem for women worldwide, despite its decline in countries where organized screening programs are in place. The morbidity of treatment and the mortality for advanced lesions are high, a frustrating situation because the cervix is accessible and a good screening test, the Pap smear, exists. HPV is an important risk factor, and the molecular evidence for its role is overwhelming. Molecular markers may soon help us decide which lesions are at highest risk of progression to invasion and which invasive lesions are likely to recur. Chemoprevention of precursor lesions is promising. An HPV vaccine could be effective in eradicating this cancer.

Biomarkers, Tumor↗
PubMed1996

Endometrial hyperplasia and endometrial cancer.

Endometrial cancer is the most frequently seen gynecologic neoplasm, but it fortunately has low mortality, which is due largely to its presentation with abnormal bleeding and its subsequent early diagnosis. The morbidity associated with therapy for early lesions is moderate. Hyperplasia with atypia should be treated as early cancers. Many molecular markers are currently under study. Markers may soon help us identify invasive lesions at higher risk of recurring and thus more suitable for adjunct therapy. Screening in the general population is not recommended, but a high-risk group that is more suitable for screening could be identified, including obese and nulliparous women, those treated with unopposed estrogen or tamoxifen, or those with family or past histories of breast or colon cancer. Development of chemoprevention with an oral contraceptive during the reproductive years is under way, and there may be a role for chemoprevention in the reversal of hyperplasias.

Biomarkers, Tumor↗
PubMed1996

Uterine sarcoma.

Sarcomas are rare tumors with unpredictable prognosis. They are treated similarly to endometrial cancers. Little is known of epidemiologic risk factors for sarcoma; similarly, little work has been performed assessing molecular alterations in sarcomas. Because of their rarity, uterine sarcomas are not suitable for screening. Chemoprevention studies might target those at risk for recurrence or a second neoplasm.

Biomarkers, Tumor↗