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Biomedical subjects

C R Campbell

Publications and source records attributed to C R Campbell.

16 recordsLinked to original sources

Transparency of one-handed Amer-Ind hand signals to nonfamiliar viewers.

Thirty non-brain-damaged adults viewed 104 videotaped Amer-Ind hand signals. The majority of these hand signals were produced with one hand; 60 originally one-handed gestures and 31 left-hand adaptations of two-handed gestures were included in the data analyses. Nineteen subjects were between the ages of 20 and 30 years (younger group), and 11 subjects were between the ages of 50 and 69 years (older group). After viewing each hand signal twice in succession, the subjects wrote at least one word for that signal's meaning. The mean percentage of one-handed signals correctly identified was 48.2%; these signals varied widely in transparency (0% to 100%). The left-hand adaptations were significantly lower in transparency than the originally one-handed signals. The younger and older subjects did not differ in the mean percentage of one-handed signals they identified correctly (49.0% and 46.4%, respectively). However, some individual hand signals were easier for the younger subjects to identify; the opposite was also true.

Adult↗

Synthesis of oligodeoxynucleotides containing analogs of O6-methylguanine and reaction with O6-alkylguanine-DNA alkyltransferase.

O6-Alkylguanine-DNA alkyltransferase (AGT) repairs the mutagenic O6-methylguanine (O6-mG) lesion by transferring a methyl group from the 6-position of guanine to a cysteine residue on the protein. The simplest possible mechanism is an SN2 process in which the cysteine displaces the methyl group off of the guanine in a concerted reaction. To probe the interactions between the protein and guanine leaving group, oligodeoxynucleotide duplexes containing analogs of O6mG were synthesized and then reacted with AGT. The analogs, which were incorporated into deoxynucleotides include O6-methylhypoxanthine (O6-mH),S6-methyl-6-thioguanine (S6mG),S6-methyl-6-thiohypoxanthine (S6mH),Se6-methyl-6-selenoguanine (Se6mG),Se6-methyl-6-selenohypoxanthine (Se6mH), O6-methyl-1-deazaguanine (O6m1DG), O6-methyl-3-deazaguanine (O6m3DG), and O6-methyl-7-deazaguanine (O6m7DG), differ from O6mG in that the heteroatoms have been replaced so that they are poorer hydrogen bond participants and proton acceptors. AGT was reacted with oligonucleotide duplexes of the sequence 5'-GGC GCT XGA GGC GTG-3' in which X was O6mG or an analog in which X was paired with C. The reactions in 50 mM Tris-HCl and 1 mM EDTA, pH7.6 and 37 degrees C, were followed by anion-exchange HPLC in 10 mM NaOH with a NaCl gradient. All detected reactions were demethylations of the oligodeoxynucleotides except for O6m3DG, which reacted in an unknown manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

The effects of residency training programs on the financial performance of Veterans Affairs medical centers.

This study examines financial performance and physician productivity in Veterans Affairs teaching hospitals following the elimination of a separate payment for the indirect costs of medical education. Financial performance of teaching hospitals in the VA system was no worse than nonteaching peers even without a teaching subsidy. Residents were found to provide patient care but this contribution to output was offset by indirect teaching costs of resident training. Physicians were less productive in teaching hospitals, possibly reflecting the time spent in training and supervising residents, while nurses were more productive. Finally, as staff size increases, the indirect costs of medical education decrease. Future downsizing of residency programs would financially benefit smaller-staffed VAMCs; larger-staffed facilities would lose.

Costs and Cost Analysis↗

HLA class I antigen expression as a measure of response to antiviral therapy of chronic hepatitis B.

HLA class I antigen expression on peripheral blood mononuclear cells was evaluated by flow cytometry in 21 HBeAg-positive patients with chronic hepatitis B. Measurements were made before, during or after treatment with recombinant interferon-alpha-2b, either given alone or after a 6 wk course of prednisone. Immunohistochemical staining for human leukocyte class I antigen was also evaluated in 28 percutaneous liver biopsy specimens either obtained before or after therapy (N = 27) and during therapy in one instance. The amount of HLA class I antigen on peripheral blood mononuclear cells varied markedly among individual patients, but the overall results indicated that the level of inducible antigen did not correlate with increments of ALT during therapy or with a virological response to therapy. Hepatocyte staining for HLA class I antigen was observed in a minority of biopsy specimens (29%) and also did not appear to predict a response or correlate with the severity of histological disease. These data do not support current theories concerning pathogenetic mechanisms in chronic hepatitis B nor do they suggest that spontaneous display of HLA class I antigen on hepatocytes or interferon-induced expression of these antigens on peripheral blood mononuclear cells is a critical determinant for a response to therapy.

Alanine Transaminase↗

Single-stranded DNA gaps, tails and loops are repaired in Escherichia coli.

Uniformly methylated heteroduplex plasmids which contained 6 mismatched regions, including loops of 24, 30, 248 and 283 nucleotides, as well as single-stranded gaps and free ends were introduced into a recombination-deficient strain of bacteria, and the products of repair were analyzed. The results indicate that these cells are capable of repairing all of these structures, although with different efficiencies. Repair of single-stranded gaps and free ends, which occurs most efficiently, is always associated with acquisition of information from the uncut strand (unidirectional repair). Regions containing single loops or twin loops were repaired at similar efficiencies. In these cases each of the two strands was capable of acting as the template for repair (bidirectional repair). At sites containing twin or substitution loops, the larger of the loops was removed twice as efficiently as the smaller loop. DNA sequencing of the repaired regions indicated that the repair is precise. The data also suggest that markers separated by only 58 nucleotides do not always segregate together indicating that repair tracts may be relatively short.

Base Composition↗

Homologous recombination involving small single-stranded oligonucleotides in human cells.

Gene modification by homologous recombination is one of the techniques that may eventually be used in gene replacement therapy. We tested whether small, synthetic single-stranded oligodeoxynucleotides are capable of participating in homologous recombination in human cells. A plasmid carrying a mutant neomycin phosphotransferase (neo) gene was cotransfected with a 40-nucleotide single-stranded oligomer that contained the wild-type neo gene sequence into human cells. Cells expressing neo were selected in the antibiotic G418. These cells contained wild-type molecules, which resulted from recombination between the two molecules. The results indicate that this approach may be useful in correcting or introducing single point mutations into the genomes of mammalian cells.

Base Sequence↗

Prednisone withdrawal followed by recombinant alpha interferon in the treatment of chronic type B hepatitis. A randomized, controlled trial.

STUDY OBJECTIVE: To determine the efficacy of a short course of prednisone followed by recombinant interferon treatment in patients with chronic type B hepatitis. DESIGN: Randomized, controlled trial with a 5-month treatment phase and a 9-month observation period after treatment. SETTING: Two referral-based university-affiliated medical centers. PATIENTS: Thirty-nine clinically stable patients with chronic type B hepatitis, all of whom were positive for hepatitis B antigen, hepatitis B virus-associated-DNA (HBV-DNA), and DNA polymerase for at least 6 months before entry. Patients included 20 heterosexuals and 19 male homosexuals. INTERVENTIONS: Eighteen patients were treated with a 6-week tapered regimen of prednisone, followed by 90 days treatment with recombinant interferon alpha-2b; 21 patients were untreated controls. Paired liver biopsy specimens of 27 patients (pretreatment and 9 months after treatment) were blindly evaluated. MEASUREMENTS AND MAIN RESULTS: Nine treated patients had a sustained loss of HBV-DNA. In addition, eight treated patients lost hepatitis B e antigen and four became negative for hepatitis B surface antigen (HBsAg). When compared with controls the differences were statistically significant for clearance of HBV-DNA and HBsAg (P = 0.035 and 0.037, respectively). Treated patients who had a sustained loss of HBV-DNA had higher initial alanine aminotransferase lower initial DNA and DNA polymerase levels, and were more frequently heterosexual. Patients who responded to treatment with the disappearance of hepatitis B e antigen and HBV-DNA had normal liver function tests and markedly improved liver histology during follow-up. CONCLUSIONS: The immunologic priming provided by a short course of prednisone used with alpha interferon may be an effective treatment for selected patients with chronic type B hepatitis.

Adult↗

Repair of single-stranded DNA nicks, gaps, and loops in mammalian cells.

We studied the ability of mammalian cells to repair single-stranded nicks, gaps, and loops in DNA duplexes. Heteroduplexes prepared from derivatives of the shuttle vector pSV2neo were introduced into monkey COS cells. After replication, the plasmids were recovered and used to transform Escherichia coli. Plasmid DNA from the recovered colonies was tested for repair at each of six different sites. We observed that mammalian cells are capable of repairing single-stranded gaps and free single-stranded ends most efficiently. Regions containing twin loops were recognized, and one of the loops was excised. Portions of the molecules containing small single loops were also repaired. Markers which were 58 nucleotides apart were corepaired with nearly 100% efficiency, while markers which were 1,000 nucleotides or more apart were never corepaired. The mechanisms involved in heteroduplex repair in mammalian cells seem to be similar to those involved in repairing DNA lesions caused by physical and chemical agents.

Animals↗

Coated vesicles contain a phosphatidylinositol kinase.

When coated vesicles (CVs) are incubated with [gamma-32P]ATP, radioactivity is rapidly incorporated into a compound identified by thin layer chromatography as phosphatidylinositol 4-phosphate. This activity has been identified in CVs isolated from bovine brain as well as from rat liver and chick embryo skeletal muscle. Phosphatidylinositol (PI) kinase is not separated from CVs during agarose electrophoresis, which produces CVs of greater than 95% purity, indicating that the activity present does not derive from contamination. The specific activity of these highly purified CVs was demonstrated to be approximately twice that of synaptic plasma membranes, further ruling out contamination from this source. The PI kinase remains associated with the vesicle upon removal of clathrin and its associated proteins and is solubilized by nonionic detergents, suggesting it is an integral membrane protein. We have been unable to demonstrate the formation of significant amounts of phosphatidylinositol 4,5-bisphosphate in any of our CV preparations. In the presence of exogenous PI, activity is stimulated, with maximal phosphorylation occurring at 0.1 mM. The enzyme appears to be maximally stimulated by 200 mM MgCl2 and 1 mM ATP and is most active at pH 7.25. Calculations indicate that, under optimal conditions, approximately 25 molecules of PIP are produced per CV within 60 s, suggesting that these structures may play an important role in cellular PI metabolism.

1-Phosphatidylinositol 4-Kinase↗

Comparative efficacy of adenine arabinoside 5' monophosphate and prednisone withdrawal followed by adenine arabinoside 5' monophosphate in the treatment of chronic active hepatitis type B.

Thirty-eight patients with chronic active hepatitis type B received antiviral therapy. In one trial, 22 patients were randomized to either no treatment or treatment with a 28-day cycle of adenine arabinoside 5' monophosphate (ARA-AMP); in a second trial, 13 patients were randomized to no treatment or treatment with two 28-day cycles of ARA-AMP separated by a 4-wk rest interval; during a third trial, 11 individuals were treated with 8 wk of prednisone therapy followed by 28 days of ARA-AMP therapy. The response rate (73%) to the regimen with prednisone was significantly greater than that achieved in the first or second trial (0% and 15%, respectively). The data indicate that the combination of short-term prednisone and ARA-AMP therapy may offer more promise for successful treatment of chronic active hepatitis type B than does ARA-AMP alone. Synergism may possibly occur by the combined effects of immune rebound provided by corticosteroid withdrawal and the inhibition of viral proliferation by ARA-AMP.

Adult↗

Immune globulin and hepatitis B immune globulin. Prophylactic measures for intimate contacts exposed to acute type B hepatitis.

We studied the relative prophylactic efficacies of recently derived immune globulin containing antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B immune globulin in 60 intimate contacts exposed to acute type B hepatitis. Forty susceptible contacts were randomly assigned to treatment with either a single intramuscular dose of immune globulin or hepatitis B immune globulin (0.06 mL/kg of body weight), following which observation was maintained over a 12-month period. Twenty additional contacts received the equivalent of twice the dose of immune globulin given to the first group, and follow-up was maintained for six months. Neither the hepatitis B virus (HBV) attack rates (11% to 19%) nor the frequency of clinical illness (0% to 4.8%) was substantially different in the three groups. When compared with average frequencies reported in the literature, significantly lower illness rates were noted for immune globulin recipients. These data indicate that currently derived immune globulin as well as hepatitis B immune globulin may confer protection from illness (le, passive-active immunity) in the setting of intimate exposure to HBV.

Acute Disease↗

Survey of hepatitis B viral markers at a public day school and a residential institution sharing mentally handicapped students.

The prevalence of hepatitis B virus markers was studied among employees and clients at a nonresidential public school for the mentally handicapped and at a privately operated residential facility. In the residential institution, 73 (80%) of 91 clients and 15 (16%) of 92 workers had positive tests for hepatitis B virus markers. Twenty-three clients, including six carriers of hepatitis B surface antigen (subtype ayw), received their education their education at the public school. Only two students (4%) who did not live at the residential institution and one employee (2%) had positive tests for hepatitis B virus markers. One of these students had acute hepatitis B infection, with hepatitis B surface antigen subtype ayw; the subtyping suggested that he had acquired the infection from one of the six carriers from the residential institution. Testing for IgM antibody to hepatitis B core antigen in single serum samples facilitated the identification of acute and chronic hepatitis B infection in children and staff of both facilities. The results show hepatitis B can be transmitted in this setting, and vaccination may be warranted for susceptible students and staff.

Adolescent↗

Spontaneous clearance and reactivation of hepatitis B virus infection among male homosexuals with chronic type B hepatitis.

Abrupt increases of alanine transaminase were observed in 6 of 23 non-treated, male homosexuals with chronic hepatitis associated with hepatitis B virus. Before this occurrence, all subjects had hepatitis B e antigen (HBeAg) and elevated DNA polymerase activity. Within 3 months, HBeAg was nondetectable in 3 subjects and elevated DNA polymerase disappeared in 4. These serologic events were not always sustained, however. In 3 subjects, reactivation of hepatitis B virus infection occurred within the subsequent 6-month period. Serologic testing for cytomegalovirus, Epstein-Barr virus, delta agent, and hepatitis B surface antigen (HBsAg) subtype showed that episodes of clearance and reactivation were not explainable by secondary infection with these agents or infection with a different HBsAg subtype. Spontaneous clearance and reactivation of hepatitis B virus infection may commonly occur among male homosexuals with chronic type B hepatitis. These phenomena should be considered when evaluating the need for treatment or interpreting the results of investigations that use anti-viral therapy.

Adult↗

Programming "loose training" as a strategy to facilitate language generalization.

This study investigated the generalization of spontaneous complex language behavior across a nontraining setting and the durability of generalization as a result of programming and "loose training" strategy. A within-subject, across-behaviors multiple-baseline design was used to examine the performance of two moderately retarded students in the use of is/are across three syntactic structures (i.e., "wh" questions, "yes/no" reversal questions, and statements). The language training procedure used in this study represented a functional example of programming "loose training." The procedure involved conducting concurrent language training within the context of an academic training task, and establishing a functional reduction in stimulus control by permitting the student to initiate a language response based on a wide array of naturally occurring stimulus events. Concurrent probes were conducted in the free play setting to assess the immediate generalization and the durability of the language behaviors. The results demonstrated that "loose training" was effective in establishing a specific set of language responses with the participants of this investigation. Further, both students demonstrated spontaneous use of the language behavior in the free play generalization setting and a trend was clearly evident for generalization to continue across time. Thus, the methods used appear to be successful for training the use of is/are in three syntactic structures.

Behavior Therapy↗