Biomedical subjects

A Gorter

Publications and source records attributed to A Gorter.

At least 37 records · Page 2Linked to original sources

PubMed1996

A controlled HIV/AIDS-related health education programme in Managua, Nicaragua.

OBJECTIVES: To evaluate the impact of a community-wide intervention to increase HIV/AIDS-related knowledge, change attitudes and increase safer-sex practices in Managua, Nicaragua. DESIGN AND SETTINGS: Household-based health education intervention trial comprising a knowledge, attitudes and practices (KAP) survey at baseline, a health education intervention and a follow-up KAP survey. Four neighbourhoods were included, two received the intervention, and the other two served as controls. Randomly selected residents aged 15-45 years were interviewed at baseline (n = 2160) and follow-up (n = 2271) using an identical questionnaire. The intervention consisted of a health education campaign that emphasized HIV transmission and condom use. OUTCOME AND ANALYSIS: Knowledge levels regarding transmission and prevention of HIV infection, self-reported use of condoms, levels of worries about HIV/AIDS and perceptions of personal risk of HIV infection. Comparisons between baseline and follow-up employed chi 2 tests with continuity correction. The influence of the intervention was examined in multivariate logistic models including an appropriate interaction term. RESULTS: Intervention and control samples were comparable with regard to sex, age, and age at first intercourse. Significantly less intervention residents had formal education (P < 0.001). At baseline, outcome variables were generally similar in control and intervention samples. Condom use increased from 9 to 16% (P = 0.003) among intervention women, but only from 9 to 11% (P = 0.5) in control women (test for interaction, P = 0.08). Among men, increases were from 31 to 41% (P < 0.001) and from 30 to 37% (P = 0.06), respectively (test for interaction, P = 0.3). Levels of worries about HIV/AIDS decreased in all groups, but perception of individual risk increased only among intervention women (test for interaction, P = 0.02). CONCLUSIONS: This household-targeted health education intervention appears to have had some effect; however, sustained efforts are needed further to improve levels of knowledge and to increase condom use in Managua.

Adolescent↗

PubMed1996

Expression of CD46, CD55, and CD59 on renal tumor cell lines and their role in preventing complement-mediated tumor cell lysis.

Nucleated cells are protected from complement-mediated injury by the expression of membrane-bound regulators of complement activation (mRCA) CD46, CD55, and CD59. Increased expression of these mRCA may be a mechanism by which tumor cells protect themselves from complement-mediated injury and prevent an inflammatory response. In the present study, we have investigated whether human renal tumor cell lines and cultured proximal tubular epithelial cells express CD46, CD55, and CD59 and whether these mRCA influence complement-mediated lysis of these cells. The expression of CD46, CD55, and CD59 was measured by flow cytometry. To determine the effect of mRCA on lysis, tumor cells were opsonized with complement activating anti-HLA class l mAb. Lysis was measured in the presence or absence of anti-CD46, anti-CD55 or anti-CD59 mAb and serum as a source of complement, using a 51Cr release assay. Flow cytometric analysis revealed that renal tumor cell lines and proximal tubular epithelial cells all express CD46, CD55, and CD59. Lysis of renal tumor cell lines in the presence of rabbit serum depended on the number of HLA class I molecules expressed by the tumor cells. Using human serum, complement-mediated lysis was decreased by at least one-third as compared with rabbit serum. The susceptibility of renal tumor cells for complement-mediated lysis could be increased up to the level observed with rabbit serum by inhibiting the function of CD59. Inhibition of the function of CD46 or CD55 with mAb directed against these mRCA had no substantial effect on lysis. We conclude from this work that renal tumor cells and proximal tubular epithelial cells express CD46, CD55, and CD59. Of these mRCA, CD59 is most efficient in preventing complement-mediated lysis of these cells. Expression of mRCA on tumor cells may influence the effectiveness of immunotherapy with tumor-associated mAb.

Amino Acid Sequence↗

PubMed1996

Membrane-bound regulators of complement activation in uveal melanomas. CD46, CD55, and CD59 in uveal melanomas.

PURPOSE: To identify the presence of membrane-bound regulators of complement activation (m-RCA) on uveal melanomas and uveal melanoma cell lines and to examine their role in the inhibition of complement-mediated lysis in vitro. METHODS: Immunohistochemistry and flow cytometric analysis with monoclonal antibodies directed against m-RCA CD46, CD55, and CD59 were applied to tissue sections of 10 uveal melanomas, three primary uveal melanoma cell lines, and one uveal melanoma metastatic cell line. A microcytotoxicity test was used for measuring antibody-dependent complement-mediated lysis. RESULTS: The tissue sections and all four uveal melanoma cell lines expressed CD46, CD55, and CD59. Complement-mediated lysis in the presence of human complement was increased after partial removal of the m-RCA CD55 and CD59 with phosphatidylinositol-specific phospholipase C from the uveal melanoma cell line 92-1. CONCLUSIONS: These results demonstrate that CD46, CD55, and CD59 are expressed in uveal melanomas and that CD55 or CD59, or both, plays a role in resistance to complement-mediated cytotoxicity. The finding that m-RCA are expressed in uveal melanomas may have implications for the effectiveness of the anti-tumor response and in the therapeutic application of monoclonal antibodies directed against tumor-associated antigens.

Aged↗

PubMed1995

Tumor heterogeneity and immunotherapy of cancer.

Tumor heterogeneity is the presence of intercellular differences, either from clonal origin or present within subpopulations of tumor cells. Recent advances in immuno-histology, flow cytometric analysis, molecular biological techniques, and tissue culture methods makes it possible to investigate tumor heterogeneity in detail. In this review data are presented to document that this hallmark of neoplastic disease results from DNA-instability and the interactions of tumor cells with their environment. The present inability to treat most patients effectively with immunotherapy may partly be due to the occurrence of tumor heterogeneity. Therefore, the heterogeneity of the tumor phenotype is discussed in conjunction with the various immunotherapeutic treatment modalities. In addition to local cytokine production by immune cells and tumor cells, and limited access of either antibodies or immune cells into the tumor, tumor heterogeneity is an important factor that determines the progress of immunotherapy of cancer. Therefore, accurate quantitative methods using antibodies and molecular probes to identify HLA-associated target peptides, tumor-associated antigens and accessory molecules, to predict which patients will have a high probability of responding to treatment, are needed.

Animals↗

PubMed1994

New chimeric anti-pancarcinoma monoclonal antibody with superior cytotoxicity-mediating potency.

The monoclonal antibodies (MAbs) 323/A3 and 17-1A both recognize a 40-kDa carcinoma-associated epithelial glycoprotein (EGP40). MAb 17-1A has been used in many therapeutic trials as an immunotherapeutic agent to combat advanced colorectal cancer, and about 5-10% overall responses have been observed. It has been shown that MAb 323/A3 has a higher affinity than 17-1A, which might be an advantageous feature for a therapeutic agent. In our immunohistological studies different reaction patterns of these two MAbs were observed, suggesting that MAb 323/A3 reacts more intensely with carcinoma cells than MAb 17-1A. This also suggests that MAb 323/A3 might be a more effective immunotherapeutic tool. Because chimerization may reduce the immunogenicity of the murine MAb 323/A3 and increase the interaction with human effector mechanisms, we developed a chimeric form of murine MAb 323/A3. MAb 323/A3 heavy and light chain variable genes were cloned and grafted onto human C gamma 1 and C kappa domains, respectively. A chimeric antibody-producing cell line was established by transfection of the chimeric constructs into a nonproducing myeloma cell. The chimeric and murine 323/A3 MAbs were evaluated for efficacy of inducing complement-mediated cytotoxicity (CMC) and mediating antibody-dependent cellular cytotoxicity against LS 180 cells derived from human colon carcinoma. Both forms were found to mediate similar levels of CMC in the presence of human complement; however, higher levels of lysis of target cells were observed with human peripheral blood lymphocytes when the chimeric 323/A3 was used. Chimeric 323/A3 mediated higher maximal cytotoxicity than chimeric 17-1A in both CMC and antibody-dependent cellular cytotoxicity assays and was equally active as chimeric 17-1A at 100- to 1000-fold lower concentrations. The superior reactivity of chimeric 323/A3 with EGP40 on carcinoma cells and its higher cytotoxicity-mediating capacity, compared to chimeric 17-1A, are important characteristics, which support further clinical studies with chimeric MAb 323/A3 in immunotherapy of carcinomas.

Adenocarcinoma↗

PubMed1993

Production of bi-specific monoclonal antibodies in a hollow-fibre bioreactor.

In the present study we have measured the feasibility of producing high amounts of bi-specific monoclonal antibodies (MAb) for therapeutic purposes using a hollow-fibre bioreactor. We have studied the isotype composition and functional capacity of an OKT3/OV-TL 3 quadroma (IgG2a/IgG1) and we have compared the production of bi-isotypic MAb in this system with tissue culture flasks or mouse ascites. Both culture supernatant and purified bi-isotypic MAb were able to enhance the cytolytic activity of a CD8+ T cell clone against ovarian tumour cell lines, demonstrating the presence of functional bi-isotypic MAb (bi-specific MAb). The total amount of immunoglobulin produced after 38 days was 375 mg. After purification by protein A affinity chromatography, 79 mg of bi-isotypic MAb (IgG1/IgG2a) was obtained. This amount of bi-isotypic MAb was similar to the amount obtained from ascitic fluid produced by 200 mice or 38 l of tissue culture flask supernatant.

Animals↗

PubMed1993

T cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model. II. Syngeneic colon carcinoma CC531 is efficiently killed by retargeted cytotoxic T lymphocytes in vitro despite limited lysis in 51Cr release assays.

We have previously described the generation of bispecific anti-TCR*anti-tumor mAb, intended for in vivo analysis of T cell retargeting in a syngeneic rat colon carcinoma model. Colon carcinoma CC531 proved to be markedly resistant to lysis by polyclonally activated, retargeted rat T lymphocytes, if measured in short term or overnight prolonged 51Cr release assays. Using cocultivation, we have now focused on another, biologically more relevant aspect of retargeted interaction: the effect on the capacity of CC531 tumor cells to survive and grow. Tumor neutralization was scored after 3 days of coculture, using a tetrazolium salt to quantify viable adherent tumor cells. Compared to 51Cr release assays, we found cocultivation to be more sensitive and more informative, as it revealed tumor cell killing at low E:T ratios, synergism of bispecific antibodies and exogenous IL-2, and free bispecific antibody-dependent recycling of effector cells. Apart from providing valuable information for future in vivo studies in this model, these data support the notion of tumor neutralization as a useful alternative for 51Cr release assays.

Animals↗

PubMed1993

The cultural construction of childhood diarrhoea in rural Nicaragua: relevance for epidemiology and health promotion.

As a component of a series of studies of childhood diarrhoea in rural Nicaragua, lay knowledge regarding the condition and its appropriate management has been investigated through semistructured interviews with 70 mothers. These data have been combined with information from focus group discussions and observations from investigators who have been resident in the study area for many years. For any episode of childhood diarrhoea, the lay nosology influences the treatment path followed. Thus for some types of diarrhoea, treatment at a health centre or health post and the use of rehydration fluids is seen to be appropriate, while for other types the use of traditional healers or home-based treatment, often explicitly without the use of rehydration fluids, is applicable. The implications of lay nosological systems for the interpretation of epidemiological studies and for the implementation of health promotion programmes are discussed.

Adolescent↗

PubMed1993

How many people actually use condoms? An investigation of motel clients in Managua.

Motels in Nicaragua are popular venues for both commercial and non-commercial sexual encounters and thus provide a potential location for the spread of sexually transmitted agents, including the human immunodeficiency virus. Condoms are known to be effective barriers against these infections, but are infrequently used by Nicaraguans. We interviewed all motel owners in one district of Managua and in five randomly selected motels ascertained, by retrieval and inspection, actual rates of condom use by clients. Six out of 26 establishments initially supplied condoms: when provided on entry to the motel condoms were used in 37% of observed encounters. Condom use can be assessed objectively in certain circumstances and this method can provide a reliable outcome measure for condom promotion programmes.

Condoms↗

PubMed1993

AIDS in Nicaragua: epidemiological, political, and sociocultural perspectives.

The AIDS epidemic in Nicaragua is several years behind that in the United States and neighboring countries of Central and South America. A combination of events, including the isolation caused by the war of the U.S.-backed Contra army against the Sandinista government, the complete economic embargo imposed on Nicaragua by the United States in 1985, self-sufficiency for blood products, and a low rate of recreational injectable-drug use, have contributed to this situation. Since the Sandinistas were defeated in the general election of 1990, people have returned to Nicaragua from areas where HIV is more prevalent, such as Honduras and the United States. It is probable that many HIV-infected persons have now entered the country. Because of the high rates of sexually transmitted diseases and cultural factors such as "machismo," HIV is likely to spread rapidly by heterosexual transmission, unless effective, culturally appropriate education and sexually transmitted disease prevention programs are implemented now.

Acquired Immunodeficiency Syndrome↗

PubMed1993

HIV/AIDS-related knowledge, attitudes, and practices among Managuan secondary school students.

In 1990, the AIDS-related knowledge, attitudes, and practices of fifth year (final year) students at four Managuan high schools were assessed. This was done by means of a self-administered questionnaire completed by 451 students (155 males, 296 females) whose mean age was 18 years. Eighty-six percent of the subjects knew AIDS was transmitted sexually, but the percentages aware of other transmission pathways and effective preventive measures were much lower. Use of condoms was cited as a preventive measure by 41% of the students, but by significantly more male respondents than female respondents (55% of the males versus 33% of the females, p = 0.0001). Sixty-four percent of all the survey subjects (90% of the males, 50% of the females) reported experiencing sexual intercourse. Sixty percent of the respondents were "very much" worried about AIDS, but only 23% considered themselves at risk of contracting the disease. Among the sexually active students, 29% of the respondents (38% of the males but only 7% of the females, p = 0.001) indicated a change in sexual behavior because of AIDS. Reported behavior change was strongly associated with concern about AIDS, but the association between reported behavior change and perception of personal risk was weak. Overall, the survey indicated that knowledge about transmission and prevention of AIDS among Managuan high school students was insufficient, especially among females, indicating a need for health education including interventions specifically targeted at female youth.

Acquired Immunodeficiency Syndrome↗

PubMed1992

Enhancement of the lytic activity of cloned human CD8 tumour-infiltrating lymphocytes by bispecific monoclonal antibodies.

We have isolated tumour-infiltrating lymphocytes (TIL) clones from a patient with renal cell cancer. The cloning frequency and the effector function were measured. No difference in cloning frequency (r2 = 0.97, frequency = 1:13) was observed between TIL expanded with allogeneic versus autologous feeder cells. Sixty-four clones expanded with autologous feeder cells and 37 clones expanded with allogeneic feeder cells were assayed for cytolytic activity on an autologous primary renal cell carcinoma (RCC) culture, an allogeneic RCC line, and on the K562 and Daudi cell lines. Most of these clones were also phenotyped. Although TIL clones expressing cytotoxic activity for RCC lines could be generated with both feeder cell preparations, none of the clones tested showed specificity for cells from autologous primary RCC cultures. However, in the presence of relevant bispecific MoAbs (alpha OC/TR) all CD8+ TIL clones tested could be induced to lyse autologous RCC cultures. Furthermore, the cytolytic activity of all CD8+ clones tested against allogeneic RCC lines could be induced or further enhanced by alpha OC/TR or CD3/G250 bispecific MoAbs. In contrast, none of the CD4+ clones tested showed lytic activity. Quantitatively the cytotoxic response in the presence of alpha OC/TR or CD3/G250 of CD8+ TIL clones against G250+ and MOv18+ cell lines appears to be associated with the level of antigen expression on the target cells. Our results suggest that: (i) expansion of TIL with allogeneic or autologous feeder cells does not effect the lytic profile of the clones; (ii) the use of bispecific MoAbs may overcome a lack of specificity of cytotoxic T lymphocytes.

Animals↗

PubMed1992

[Concepts about AIDS among the adult population of Managua].

Nicaragua has the lowest prevalence of AIDS in Central America. In other countries where AIDS is more prevalent, the first epidemic of asymptomatic infections with human immunodeficiency virus (HIV) and the second of clinical cases of AIDS have been followed by a third epidemic of fear and discrimination. In December 1989 a study was conducted to investigate knowledge and attitudes about AIDS in a sample of 287 adults in Managua. Most of the interviewees had heard of the disease from newspapers and television, and more than 90% understood how HIV was principally transmitted. However, between one-third and one-half the interviewees believed that HIV could be transmitted by causal contact such as kissing (53%) or by mosquito bites (49%). In addition, the majority considered that isolation of HIV-infected persons and control of immigration into the country would be effective measures for preventing the spread of the disease. These results are similar to findings from studies carried out in other countries of Latin America where the HIV and AIDS epidemics started much earlier. This would suggest that the so-called "third epidemic" of discrimination and fear is affecting Nicaragua in advance of the other two.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Methods for the detection of anti-endothelial antibodies by enzyme-linked immunosorbent assay.

In order to obtain a routine simple screening test for the detection of anti-endothelial antibodies (AEA) we developed a highly reproducible and sensitive enzyme-linked immunosorbent assay (ELISA) on fixed endothelial hybridoma cells. Detection of AEA with this type of monolayer appeared to be superior to ELISAs with monolayers of human umbilical vein endothelial cells, unfixed endothelial hybridoma cells or assays with membranes of endothelial cells. Glutaraldehyde treated endothelial hybridoma cells are most appropriate for use in ELISA procedures to detect AEA because the endothelial hybridoma cells are easy to culture, form a constant antigenic source and when plated and fixed to microtitre plates they can be stored without losing their ability to bind AEA.

Arthritis↗

PubMed1991

AIDS in Nicaragua.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Why do child mortality rates fall? An analysis of the Nicaraguan experience.

A comprehensive review of available sources of mortality data was undertaken to document the changes that have occurred in infant mortality in Nicaragua over the last three decades. It was found that a rapid fall in infant mortality commenced in the early 1970s and has continued steadily since. Trends in several different factors which might have led to this breakthrough were examined including: income, nutrition, breastfeeding practices, maternal education, immunizations, access to health services, provision of water supplies and sanitation, and anti-malarial programs. Of these, improved access to health services appears to have been the most important factor. At a time when the number of hospital beds per capita was dropping, increasing numbers of health care professionals, particularly nurses, were becoming available to staff primary health care facilities built in the 1960s. These were provided at least partly in response to the growing political turmoil enveloping the nation at that time. Certain Nicaraguan cultural attributes may have added to the impact of the reforms. Efforts in the field of public health made since the 1979 insurrection appear to have maintained the decline in child mortality.

Breast Feeding↗

PubMed1990

Rat polymeric IgA binds C1q, but does not activate C1.

Immune complexes, prepared with monoclonal rat IgA antibodies directed against DNP, activate the alternative pathway of the complement system in rat serum. In this study, the interaction of these monoclonal IgA antibodies with the classical pathway of complement was investigated. Monoclonal polymeric IgA (p-IgA) was shown to inhibit the IgG2b-mediated classical pathway-dependent lysis of TNP-coated sheep red blood cells. In addition, the binding of C3 to solid phase IgG2b immune complexes was inhibited by p-IgA. Monoclonal monomeric IgA (m-IgA) was much less efficient in this respect. To further analyse the effect of p-IgA on the activation of the classical pathway by IgG2b immune complexes, the interaction of p-IgA with C1 was studied. It was found that p-IgA antibodies bind C1q. No species-specificity was observed, since both rat and human C1q were bound. Whereas binding of C1q in C1 to IgG2b resulted in activation of C1, binding to p-IgA did not. The binding of C1q to both p-IgA and IgG2b could be inhibited by monoclonal antibodies directed against the globular heads of C1q, but not by monoclonal antibodies directed against the collagen tail. The formation of insoluble p-IgA immune complexes was inhibited in the presence of rat serum or C1. These studies indicate that C1q binds to p-IgA by its globular heads, and thereby may modulate classical pathway-mediated reactions such as the inhibition of immune precipitate formation.

Animals↗

PubMed1990

The involvement of Kupffer cells in the clearance of high molecular weight rat IgA aggregates in rats.

In the present study the clearance kinetics and tissue distribution of aggregated 125I-labelled monoclonal rat IgA [( 125I] AIgA) of different sizes were studied in rats. Soluble [125I]AIgA disappeared from the circulation in a biphasic manner with an initial rapid distribution half-life (T1) and a second slower half-life (T2). T2 was directly related to the size of the aggregates. High molecular weight [125I]AIgA, containing 10-12 IgA molecules per aggregate [( IgA]10-12), was cleared much faster than low molecular weight aggregates. The main site of clearance was the liver. The larger the size of the AIgA, the more degradation products were found in the circulation. After injection of [IgA]10-12, non-parenchymal cells (NPC) contained three times more radioactivity than parenchymal cells (PC) (NPC:PC ratio 3.06 +/- 0.96). Ratios of 0.82 +/- 0.03 and 0.62 +/- 0.12 were observed when [IgA]5-6 and [IgA]2 were injected respectively, suggesting a greater role for Kupffer cells in the clearance of large-sized IgA aggregates. Kupffer cells were shown to be the main cells for localization of large-sized AIgA established by immunohistochemical staining on liver cryostat sections.

Animals↗