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S Fossum

Publications and source records attributed to S Fossum.

At least 19 recordsLinked to original sources
PubMed1992

Targeting antigens to antigen presenting cells.

Antigen may be targeted to antigen presenting cells (APC) by conjugating the antigen to monoclonal antibodies directed against surface molecules on APC. By now several laboratories have shown that immunotargeting enhances humoral responses, depending upon the targeted ligand or cell type, with low doses of antigen and without the use of adjuvants. There is also preliminary evidence that the method may be used to bias immune responses in desired directions, possibly also to induce tolerance. In addition to its use as an experimental tool for exploring immune reactions the method could in the future also be clinically important, e.g. in vaccination. In this article we give a brief account on work so far published with this novel method and discuss possible mechanisms behind its immunopotentiating effects.

Animals↗
PubMed1991

Contact activation factors in plasma from pregnant women--increased level of an association between factor XII and kallikrein.

The plasma levels of FXII, prekallikrein (PK), and high- and low molecular weight kininogens (HK and LK) were studied in pregnant women in the last trimester and in non-pregnant controls. FXIIa and plasma kallikrein were assayed in acetone-treated citrated plasma (CPLa) with the tetrapeptide S-2222 as substrate, using soybean trypsin inhibitor and corn inhibitor to exclude kallikrein and FXIIa respectively. No difference in PK-level could be registered for the two kinds of plasma, but the level of FXII had increased to about 150% in the pregnancy plasma. No difference in HK-level was observed, whereas the LK-level was significantly higher in pregnancy plasma, about 250% and 160% in rocket immunoassay and bioassay respectively. In fractions from gel filtration of plasma acetone-activated in the presence of benzamidine (BPLa), kallikrein was assayed as S-2302 amidase, HK and LK were measured in rocket immunoassay, and HK and FXII were studied in PAGE immunoblot experiments. In contrast to previous results obtained upon gel filtration of CPLa, not only kallikrein and HK, but in addition also FXII now appeared together in the same fractions and as two separate peaks. One peak eluting in early fractions (gel mol. wt. 300-400 KD), and one late eluting peak of proteins adsorbed to the gel material. The first peak was notably marked in pregnancy plasma. The results provide support for the assumption of an association in plasma between the three contact activation factors studied.

Adult↗
PubMed1991

The MRC OX-47 antigen is a member of the immunoglobulin superfamily with an unusual transmembrane sequence.

The MRC OX-47 monoclonal antibody recognizes a membrane antigen present at low levels on many lymphocytes but whose expression is markedly increased on activation with mitogens. cDNA clones for the OX-47 antigen were isolated from an expression library and the protein sequence deduced. It contains a leader sequence giving a mature protein of 251 amino acids with a single putative transmembrane region, a cytoplasmic domain of 40 amino acids and an extracellular domain of 187 amino acids that contained two immunoglobulin-like domains. The putative transmembrane sequence includes a glutamic acid residue within the hydrophobic sequence. The presence of acidic residues within the hydrophobic sequence of transmembrane sequences usually indicates association with other polypeptides and this is predicted for the OX-47 antigen. A sequence of 37 amino acids that included all the transmembrane region was identical to that of the chicken HT7 antigen present on endothelium in brain and erythroblasts. The level of protein sequence identity in the Ig-like domains was lower but HT7 is almost certainly the chicken homologue of the rat OX-47 antigen. The ligand and function of the molecule are unknown. In addition to lymphoblasts the OX-47 antigen was localized on a variety of other cell types including various immature cells, endothelia and cells with excitable membranes.

Amino Acid Sequence↗
PubMed1991

Allospecific recognition of hemic cells in vitro by natural killer cells from athymic rats: evidence that allodeterminants coded for by single major histocompatibility complex haplotypes are recognized.

We have previously shown that large granular lymphocyte (LGL)-enriched cell populations have the capacity to spontaneously recognize and kill allogeneic small lymphocytes and bone marrow cells (BMC) in vitro in certain strain combinations of rats. Here, we have studied the alloreactivity of natural killer (NK) cells from PVG nude (RT1c) rats against a panel of major histocompatibility complex (MHC) incompatible hemic cells. Both lymphocytes and BMC from the AO (RT1u), DA (RT1a), BN (RT1n) as well as the MHC-congenic PVG-RT1u (RT1u) rat strains were efficiently killed in vitro, whereas cells from syngeneic PVG rats were spared. The structures recognized on lymphocytes and BMC were probably similar since the two cell populations inhibited each other in cross-competition experiments. A number of features aligned the alloreactive effector cells with NK cells and not T cells. (a) Only about 5% of the effector cells from nude spleens expressed the T cell antigens CD3, CD5 or T cell receptor (TcR) alpha/beta whereas greater than 50% of the cells expressed markers present on NK cells (CD2, CD8, OX52 and the rat NK cell-specific marker NKR-P1 recognized by the monoclonal antibody 3.2.3). (b) The alloreactive cells were granular since pretreatment of nude spleen cells with the lysosomotropic agent L-leucine methyl ester which eliminated LGL, simultaneously abolished the cytolysis of both allogeneic lymphocytes and YAC-1 tumor cells. (c) Nude spleen cells stimulated with human recombinant interleukin 2 for 1 week in vitro generated large granular proliferating cells which were CD3-, CD5-, TcR alpha/beta-, but greater than 95% 3.2.3+. These cells efficiently killed allogeneic hemic cells from the same rat strains as did freshly isolated effector cells. (d) The cytolysis of allogeneic hemic cells could effectively be inhibited with unlabelled NK-sensitive (YAC-1 and K-562), but not NK-resistant (Roser leukemia) tumor cells. Cross-competition studies showed that PVG nude NK cells discriminated between AO, BN and DA BMC, suggesting that different alloantigens were positively recognized by subsets of NK cells. The mode of inheritance of the allodeterminant specifically recognized on AO BMC was investigated in crosses and backcrosses between AO and BN or DA rats. A gene dosage effect was observed in that this determinant was expressed at a slightly reduced level in F1 hybrids.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Antigen targetting with monoclonal antibodies as vectors--II. Further evidence that conjugation of antigen to specific monoclonal antibodies enhances uptake by antigen presenting cells.

Immunization of rats with haptenized monoclonal antibodies (mAbs) against accessory cells enhances anti-hapten antibody responses. To see whether the mAb-conjugates really targetted the antigen (hapten) to the antigen presenting cells, we have investigated the lymph node distribution of locally injected radiolabelled conjugates. Compared with control conjugates, i.e. haptenized non-binding mAbs, a much larger proportion of the specific conjugates were retained in the draining lymph nodes. Whereas control conjugates were rapidly phagocytosed and degraded by macrophages, the specific conjugates were associated with the targetted accessory cells, which were radiolabelled for extended periods. Haptenated MRC OX6 (anti-MHC class II) gave strong labelling of interdigitating cells (IDC) in the paracortex with 70% of IDC still labelled by 4 days and 15% by 16 days following injection. By Western blots intact OX6 conjugates were still detected in the draining lymph node as long as 3 days after injections, whereas control conjugates were hardly detectable even by 24 h. The findings substantiate the idea that mAbs can be exploited for vectorial transport of antigens to accessory cells.

Adjuvants, Immunologic↗
PubMed1991

Anaemia in elderly patients. Incidence and causes of low haemoglobin concentration in a city general practice.

Haemoglobin concentration was determined in all patients (530) over 70 years of age in a general practice in Oslo during an eight month period. 72 had anaemia and were investigated further. Iron deficiency was found in 13 patients and was most often caused by gastrointestinal blood loss. Chronic diseases, particularly chronic infections and rheumatoid arthritis, were responsible for anaemia in 34 patients. Renal failure caused anaemia in 14 patients. In 10 patients we found no explanation for the anaemia. Nine patients with a previously undiscovered disease were found, six of whom could be offered some kind of treatment. We conclude that anaemia in elderly patients in general practice is often caused by chronic diseases. The main cause of iron deficiency is blood loss, and routine prescription of iron is not justified in this age group. The therapeutic benefit from routine measurement of haemoglobin concentration is small and the test should be used selectively.

Age Factors↗
PubMed1990

[The health consultant. A new profession].

The facilitator is a new profession developed first in Oxfordshire in 1982 for the purpose of promoting prevention in primary health care. There are at present more than 100 facilitators in Britain and some in Holland, most of them working on prevention of cardiovascular disease, but recently some also in connection with the HIV-epidemic. In brief, the task of the facilitator is to bridge the gap or establish a new channel of communication between the general practitioner and his coworkers on the one side and the specialized health service on the other. The paper describes the tasks and working methods of the facilitator in some detail, particularly with respect to prevention of HIV-infection and control and care of HIV-positive and AIDS-sick patients in general practice. A trial project involving facilitators is planned in Oslo.

Acquired Immunodeficiency Syndrome↗
PubMed1990

T cell receptor-bearing cells among rat intestinal intraepithelial lymphocytes are mainly alpha/beta+ and are thymus dependent.

Rearrangement of both the beta and gamma chain T cell receptor (TcR) genes was detected in intestinal intraepithelial lymphocytes (IEL) from normal euthymic rats. Flow cytometric analyses showed that about 73% of the IEL were CD3+ (1F4) and that 67% were TcR alpha/beta+ (R73). About 5% of the IEL were found to be CD3+, TcR alpha/beta- in double-labeling experiments suggesting that a small fraction of IEL in the rat express the alternative TcR gamma/delta. More than 70% of the IEL were granular implying that many CD3+ IEL are granular. In IEL from athymic nude rats no rearrangement of either the TcR beta or gamma chain genes or surface expression of CD3 or TcR alpha/beta was detected despite the fact that about 95% of the cells were granular and morphologically similar to those in normal rats. Taken together our data suggest that the majority of IEL in the rat express the conventional TcR alpha/beta and that TcR-bearing cells in the gut epithelium are thymus dependent.

Animals↗
PubMed1990

Modulation of immune responses with monoclonal antibodies. I. Effects on regional lymph node morphology and on anti-hapten responses to haptenized monoclonal antibodies.

Repeated injections of monoclonal antibody (mAb) culture supernatants into rat footpads increased the weights of the draining lymph nodes. Immunostained freeze sections showed that injection of MRC OX2, a mAb reacting with rat follicular dendritic cells and MRC OX7 (anti-Thy-1.1), led to gross hypertrophy primarily of the follicular areas, whereas MRC OX6 (anti-rat major histocompatibility complex class II molecules) resulted in selective stimulation of the paracortex. These findings indicate that mAb, when conjugated to certain antigens, would modulate the immune response to these antigens. Consequently, the mAb were conjugated with fluorescein isothiocyanate (FITC) and the humoral response against the hapten measured. The primary anti-FITC antibody response was tenfold stronger than after stimulation with FITC conjugated to a conventional carrier such as ovalbumin, and had some characteristics of a secondary response: a fast increase of IgG level to very high titers and a long duration without further amplification at later antigen challenges.

Adjuvants, Immunologic↗
PubMed1990

Characterization of the MRC OX40 antigen of activated CD4 positive T lymphocytes--a molecule related to nerve growth factor receptor.

The antigen recognized by the monoclonal antibody (mAb) MRC OX40 is present on activated rat CD4 positive T lymphocytes but not other cells. cDNA clones were isolated from an expression library using the MRC OX40 mAb and the protein sequence for the OX40 antigen deduced. It contains a typical signal sequence and a single putative transmembrane sequence of 25 predominantly hydrophobic amino acids giving an extracellular domain of 191 amino acids and a cytoplasmic domain of 36 amino acids. The sequence of the extracellular domain includes a cysteine-rich region with sequence similarities with the low affinity nerve growth factor receptor (NGFR) of neurons and the CD40 antigen present on human B cells. Within this region three cysteine-rich motifs can be recognized in OX40 compared with four similar motifs in both NGFR and CD40. OX40, CD40 and NGFR constitute a new superfamily of molecules with expression including lymphoid cells (OX40, CD40) and neuronal cells (NGFR). This is reminiscent of the immunoglobulin superfamily whose molecules are variously found at the surface of lymphoid or brain cells or both.

Amino Acid Sequence↗
PubMed1990

Non-adaptive cellular immune responses as studied in euthymic and athymic nude rats. Spontaneous rejection of allogeneic lymphoid cell grafts by natural killer (NK) cells.

The athymic nude (rnu) rat lacks a functional thymus and normal alloreactive T cells. These animals, therefore, have been widely used as tools for studying thymus-independent immune responses. The absence of functional T cells would, to most investigators, indicate that these rats have a defective cellular immune defence. However, although rnu rats accept organ allografts infinitely, they are nevertheless capable of rejecting allografts consisting of lymphocytes or bone marrow cells with increased vigour, and this via antibody-independent mechanisms. These rejection phenomena have operationally been termed allogeneic lymphocyte cytotoxicity (ALC) and allogeneic bone marrow cell cytotoxicity (ABC). Unlike organ allograft immunity this kind of rejection requires no presensitization of the recipient and is surprisingly rapid: it commences within a few hours of i.v. injection of the allogeneic cells and is usually complete by 24 h. Moreover, products coded for by genes within, or closely linked to the major histocompatibility complex (MHC), are clearly involved in the interaction between effector and target cells, as grafted cells from MHC-congenic rat strains are vigorously rejected. In contrast to the defective T cell immune responses in athymic nude rats, the natural killer (NK) cell function is not impaired, and it has been suggested that the spontaneous rejection of MHC-incompatible lymphohematopoietic cells is in fact mediated by NK cells. If the MHC antigens themselves serve as targets in this kind of allorejection, this hypothesis is in apparent contrast with the prevailing view that recognition by NK cells is not guided by, or directed against, MHC-antigens on the target cell surface. Aging athymic nude mice and rats generate cells that rearrange and express T cell receptor (TCR) genes, and this has raised the possibility that T cells or T-like cells in athymic nude animals are responsible for ALC and ABC. This possibility urged the device of an in vitro test system for identification and further characterization of the effector cells in these rejection phenomena. Under appropriate conditions, cells from the rnu rat spleen or liver with natural killer function, i.e. the ability to lyse certain kinds of tumor cells in vitro, are also spontaneously cytotoxic for allogeneic small lymphocytes and bone marrow cells in vitro. Furthermore, these cells can be grown in vitro in the presence of interleukin 2 (IL-2) to generate populations of lymphokine-activated killer (LAK) cells, and these cells have the same spectrum of alloreactivity in ALC and ABC as the native NK cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Alloreactive lymphokine-activated killer cells from athymic nude rats do not express CD3-associated alpha/beta or gamma/delta T cell receptors.

Lymphokine activated killer (LAK) cells from athymic nude rats, previously shown to selectively kill MHC-incompatible small lymphocytes in vitro, were examined for rearrangement and expression of genes for the T cell antigen receptors. Southern blots showed no rearrangement of the TCR beta-chain genes, and Northern blots showed transcription only of truncated 1.0 kb beta-chain messages, but not of full-length, 1.3 kb beta-chain mRNA. Transcription of the alpha-chain of the TCR could not be detected, and surface staining with the mAb R73 showed no expression of the rat TCR alpha/beta heterodimer. Transcripts hybridizing with a rat TCR C gamma probe were detected on Northern blots, but probes for all presently characterized mouse V gamma genes failed to hybridize to the same filters, indicating that the C gamma-containing transcripts probably were from non-rearrangement genes. CD3 delta- and epsilon-chain transcripts could not be detected by Northern blot analysis. Less than 2% of the cells stained with the anti-rat CD3 monoclonal antibody 1F4, and incubation with 1F4 had no effect on the alloreactivity of nude rat LAK cells. We have previously shown that immunoglobulin is not involved in the killing of the allogeneic lymphocytes. The most likely interpretation of these results is therefore that nude rat LAK cells express a novel receptor structure involved in allorecognition.

Animals↗
PubMed1989

[HIV screening of pregnant women and women seeking abortion. A preventive measure against HIV?].

In our opinion, screening of women seeking abortion and pregnant women does not benefit the work of HIV-prevention. Of the 115,600 tested from September 1987 to December 1988 in Norway, four new and HIV-positive and 92 false positive women were diagnosed. From the time screening started in September 1987 to the end of February 1989, the program has cost NOK 6-7 million. The prevalence of HIV among pregnant and abortion-seeking women is too low, and the problems associated with false positive results are too great for the project to be recommended. Pregnant women and women seeking abortion, and their partners, should be given the possibility of taking the HIV-test in the same manner as other low prevalence groups, where information and counselling are integrated and confidentiality is secured.

Abortion Applicants↗
PubMed1989

[Norwegian nomenclature in immunology].

Immunology represents one of the medical disciplines that has witnessed the fastest growth in new knowledge in recent decades. In the international journals the new concepts are introduced using English terminology. Norwegian immunologists are almost exclusively exposed to English immunological literature, and are therefore prone to adopt English rules of syntax when translating this literature into Norwegian. Two years ago a nomenclature-committee was established, with the mandate to ensure improved translations and, where relevant, to point out rules of syntax. The article presents the results from the work of this committee.

Allergy and Immunology↗
PubMed1989

[Heterosexual transmission of HIV--a predominantly female problem?].

Heterosexual dissemination of HIV is increasing in Norway. Women are apparently more exposed than men. 70% of Norwegian HIV-cases attributed to domestic heterosexual transmission are women. The two groups of sexual partners that most frequently infect Norwegian women with HIV are drug abusers and men from countries with a high prevalence of the disease. Physicians ought to be aware of this increase in heterosexual HIV-contamination, especially among younger women, so that they can undertake the public-health measures needed to delimit the spread of the disease. In particular, they should include sexual anamnesis in their examination of all cases where HIV-infection is a possibility.

Acquired Immunodeficiency Syndrome↗