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Biomedical subjects

N Barrett

Publications and source records attributed to N Barrett.

At least 19 recordsLinked to original sources

Preparing psychiatric rehabilitation specialists through undergraduate education.

This report outlines the development of a new undergraduate psychiatric rehabilitation curriculum designed to prepare students for entry-level positions. The program, which opened in January 1993, has graduated 25 students with Associate of Science degrees in Psychiatric Rehabilitation as of May 1995. The need for the program, a brief overview of its curriculum, and the evaluation of its impact on students and agencies are presented.

Adult↗

An ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis.

Advances in the management of the pulmonary complications of cystic fibrosis may result in an increasing prevalence of patients with chronic liver disease which may, therefore, become more important in the long-term management of cystic fibrosis patients. However, no simple and reliable test is available for the diagnosis of liver disease in cystic fibrosis. In particular percutaneous liver biopsy is highly inaccurate and potentially dangerous. Imaging techniques, including real-time ultrasound scanning, have been used to evaluate the hepato-biliary system in cystic fibrosis and may represent the best available techniques for documenting hepatic involvement. The purposes of this study were to construct an ultrasound scoring system using three cardinal features of hepatic ultrasound in cystic fibrosis: coarseness of the parenchyma, nodularity of the liver edge and increased periportal echogenicity, to enable the accurate, early diagnosis of liver involvement in cystic fibrosis. The scoring system was validated by correlating the results against ultrasound markers of portal hypertension, clinical and haematological data. The scoring system proved to be reproducible and to correlate well with the markers of hepatic disease detailed above. The results also suggest that the scoring system may allow the identification of patients with pre-cirrhotic chronic liver disease and so may prove of value in selecting a sub-group of patients more likely to respond to therapy.

Adult↗

Immunization of chimpanzees with recombinant gp160, but not infection with human immunodeficiency virus type 1, induces envelope-specific Th1 memory cells.

The human immunodeficiency virus (HIV) type 1 envelope protein (recombinant [r] gp160)-induced T cell lymphokine release pattern of chimpanzees immunized with HIVIIIB rpg160 tested and compared with rpg160-induced lymphokine releases of T cells from unimmunized, HIV-1-infected chimpanzees. The results showed that infection of chimpanzees with HIV-1 did not induce rgp160-specific memory T cells (as evidenced by the lack of Th1 and 2 type lymphokine releases after rgp160 stimulation). In contrast, T cells of rgp160-immunized chimpanzees released Th1 type lymphokines upon stimulation with rgp160 of HIVIIIB, HIVMN, and HIVRF. release was comparable whether chimpanzees were immunized with rgp160 only or also challenged with HIV-1 and protected or not protected. Thus, rgp160 immunization leads to generation of Th1 type memory cells. Whether Th1 type responses contribute to protection against HIV-1 infection has yet to be clarified.

Animals↗

A broadly neutralizing human monoclonal antibody against gp41 of human immunodeficiency virus type 1.

We have established a hybridoma clone, designated 2F5, secreting a neutralizing human monoclonal antibody (MAb) specific for gp41 of human immunodeficiency virus type 1 (HIV-1). The epitope of MAb 2F5 was mapped to amino acid sequence Glu-Leu-Asp-Lys-Trp-Ala on the ectodomain of gp41. In this study different in vitro test systems were used to characterize the neutralizing properties of MAb 2F5. In syncytium inhibition assays, fusion inhibition experiments, and neutralization assays on different HIV-susceptible cells (H9, U937, and peripheral blood mononuclear cells) MAb 2F5 showed broad-spectrum neutralizing capacity against HIV-1 laboratory isolates IIIB, MN, RF, and SF2. In addition, primary isolates from AIDS patients were also neutralized.

Acquired Immunodeficiency Syndrome↗

Mutations of Ki-ras and p53 genes in colorectal cancer and their prognostic significance.

The series of genetic changes leading to malignancy in colorectal cancer is well reported. This includes mutational activation of the proto-oncogene Ki-ras and mutation/deletion of the p53 tumour suppressor gene. The frequency of these mutations was investigated in a panel of 52 colorectal cancer patients using a combination of immunocytochemistry and non-radioactive, digoxigenin-labelled in situ hybridisation. Sixty two per cent (32 of 52) of the study population were positive for p53 overexpression and 36% (19 of 52) positive for Ki-ras mutation. Twenty seven per cent (14 of 52) of the patients expressed both mutations. Mutation of either the p53 or the Ki-ras gene did not correlate with Dukes's stage, tumour differentiation or 5 year survival rate of the patients. Most of the rectal carcinoma specimens (11 of 15) showed p53 over-expression but the significance of this was not supported statistically. Thus detection of molecular changes is becoming more amenable to incorporation into routine histological carcinoma assessment because of the advent of non-radioactive labelling in in situ hybridisation and antibodies suitable for paraffin wax embedded specimens. The significance of these mutations in disease prognosis, however, remains questionable.

Colonic Neoplasms↗

High level expression of active human prothrombin in a vaccinia virus expression system.

We have worked out an efficient and time saving procedure for the expression of recombinant human prothrombin. The glycoprotein was expressed in the vaccinia virus expression system in several mammalian cell lines. The kidney cell lines Vero and BHK and the human cell line Hela were found to efficiently secrete prothrombin. Expression level of 3-4 micrograms of factor II per 10(6) cells per day corresponding to 18-23 mU per 10(6) cells per day were achieved. Since the expression levels obtained with the vaccinia virus/Vero cell system were comparable to those obtained in amplified transformed CHO cells it provides an alternative system for the efficient expression of human prothrombin and may allow to further elucidate structure-function relationships of (pro)thrombin and its various effectors.

Amino Acid Sequence↗

Dental caries experience and prevalence of children afraid of dental treatment.

The aim of this study was to examine the clinical outcome with regard to dental caries of high self reported dental anxiety in a group of Scottish secondary schoolchildren. 1103 children participated in the study, mean age 14 yr (sd 0.35 yr), and the prevalence of high dental anxiety was 7.1% (95% CI = 5.6%, 8.6%). When these children were compared with their contemporaries their DMFT and all its components were higher but only the mean MT reached statistical significance after adjusting for gender and social class. Children with a high dental anxiety were 62% more likely to have at least 1 missing tooth due to caries. In addition this group when compared to the rest of the study population, had a significantly lower mean number of teeth fissure sealed and a lower proportion of children with sealants. No similar trend was obvious for children who had a high general fear. The dentally anxious more accurately perceived their treatment need and were more likely to defer, cancel or not turn up for dental appointments.

Adolescent↗

Immunization of chimpanzees with the HIV-1 glycoprotein gp160 induces long-lasting T-cell memory.

The goal of the present study was to investigate the antigen-specific T-cell response to the recombinant HIV envelope glycoprotein (gp160) and to test the effect of various adjuvant formulations on the efficiency of T-cell priming as well as on magnitude and longevity of the gp160-specific T-cell response. Our studies revealed that, in combination with an appropriate adjuvant (lipid-based adjuvant or mineral carrier complex), immunization with recombinant gp160 led to the appearance of gp160-primed T cells. The T-cell response obtained was substantial (proliferative response of greater than 100,000 delta dpm after one primary and two booster immunizations), gp160-specific (proliferation only in response to gp160, no proliferation after addition of a mock gp160 preparation), and long-lasting (T cell responses of greater than 50,000 delta dpm were observed more than one year after the last booster). The results presented here differ from those of previous studies in that they show the presence of substantial and long-lasting T-cell memory toward the immunogen gp160. Therefore further investigations on the use of these preparations as HIV candidate vaccines appear to be justified.

Adjuvants, Immunologic↗

Characterization of a vaccinia-derived recombinant HIV-1 gp160 candidate vaccine and its immunogenicity in chimpanzees.

The human immunodeficiency virus (HIV-1) envelope glycoprotein gp160 was produced in large-scale microcarrier cultures of Vero cells, using a system involving coinfection with two recombinant vaccinia viruses. The immunogenicity of this material was studied in conjunction with a number of different adjuvant formulations, and chimpanzees were then immunized with gp160 in conjunction with Al(OH)3, Al(OH)3 and sodium deoxycholate, and a lipid-based adjuvant. The Al(OH)3-gp160 vaccine formulation elicited very poor immune responses in two chimpanzees, and these animals were further immunized with gp160 in conjunction with a lipid-based adjuvant. Immunization with the latter formulation lead to induction of high-titer neutralizing antibodies, and, following challenge with HIV-1, one chimpanzee demonstrated no evidence of virus infection over a period of 3 years. The second chimpanzee, which had previously been infected with non-A, non-B hepatitis, and two animals immunized with gp160 with Al(OH)3 and deoxycholate were not protected against challenge.

AIDS Vaccines↗

[AIDS vaccines: an enigma in vaccine development].

The principles of viral vaccine development and the immune responses to vaccination are described. An effective vaccine should stimulate both cellular and humoral immune responses to provide lasting protection against infection and disease. We describe specific problems associated with the development of an AIDS vaccine i.e. lack of experience with human retroviruses, the integration of the HIV genome in cellular DNA, HIV infection of critical cells in the immune system, persistence of HIV in the brain, large variations in the virus envelope gene, immune interactions with the CD-4 protein and the generation of infection enhancing antibodies. The strategies of AIDS vaccine development are discussed and the candidate vaccines are described with a report on the status of each vaccine trial in progress.

Acquired Immunodeficiency Syndrome↗

Clozapine: a new drug for schizophrenia.

Clozapine, a new drug for schizophrenia, was recently released for use. We have described the drug and nursing care involved for patients who are on acute inpatient unit for a trial of the drug. From our early observations, clozapine appears to be a promising drug for patients who have not responded to standard neuroleptics.

Adolescent↗

Efficiency of the polymerase chain reaction for the detection of human immunodeficiency virus type (HIV-1) DNA in the lymphocytes of infected persons: comparison to antigen-enzyme-linked immunosorbent assay and virus isolation.

Seventy-one human immunodeficiency virus type (HIV-1)-positive patients were investigated by polymerase chain reaction (PCR), virus isolation, and antigen detection for the existence of HIV in blood. The identification of HIV DNA by PCR, using three different pairs of primers, yielded a clearly higher detection rate (86%) than with two primer pairs (75%) and was far more sensitive than virus isolation (45%) and antigen ELISA (14%). The PCR-negative results were clearly correlated to asymptomatic clinical stages. However, there was a limited correlation between the clinical stage of disease and the amount of HIV DNA that could be detected in equal numbers of CD4+ cells from different patients, which might be due to their treatment with azido-thymidine (AZT).

Acquired Immunodeficiency Syndrome↗

Large-scale production and purification of a vaccinia recombinant-derived HIV-1 gp160 and analysis of its immunogenicity.

The human immunodeficiency virus (HIV-1) envelope gene was expressed in large-scale microcarrier cultures of Vero cells using a system involving coinfection with two recombinant vaccinia viruses. One recombinant contained the bacteriophage T7 RNA polymerase gene under control of a vaccinia virus promoter. The second contained the HIV-1 gp160 gene flanked by T7 promoter and termination sequences. The protein was expressed on the surface of infected cells, and it was shown to have a molecular weight of 160 kD and to react with gp41 and gp120 specific monoclonal antibodies. After purification by successive affinity and ion-exchange chromatography, the protein was demonstrated to be present in a particulate form with a diameter in the range of 15-30 nm. When injected into goats a high-titer gp160 specific antibody response was elicited and group-specific neutralizing activity could be demonstrated in vitro. The immunogenicity of the protein was also studied in conjunction with a number of adjuvant formulations, and the highest potency in mice was obtained using a preparation with 0.2% Al(OH)3 and 0.25% deoxycholate.

Adjuvants, Immunologic↗

Subclavian stenosis: a major complication of subclavian dialysis catheters.

Subclavian catheterisation is frequently used for acute vascular access for haemodialysis and is thought to rarely result in long-term clinical problems. Venography in 36 cases, however, revealed subclavian stenosis in 18 (50%), of whom five developed clinical problems. The incidence of subclavian-vein stenosis was related to the duration of catheterisation (P less than 0.05). It may also be more common in black patients. Subclavian catheterisation is therefore not necessarily an ideal form of acute vascular access.

Catheterization, Central Venous↗