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Biomedical subjects

S Haahr

Publications and source records attributed to S Haahr.

At least 55 records · Page 3Linked to original sources

In vitro susceptibilities of normal human skin fibroblasts to oncoviruses, and the decreased susceptibility to HSV of fibroblasts from untreated Hodgkin's patients.

Fibroblast cultures established from the skin of 56 healthy controls and 15 untreated Stages I and II Hodgkin's patients (HD) were studied in their 3rd, 4th and 5th in vitro passage with respect to transformation with Simian sarcoma virus (SSV) and SV40 and with respect to replication of herpes simplex virus (HSV) Types 1 and 2, pox virus and interferon release. Susceptibility to the 5 viruses varied independently, except for an inverse correlation between susceptibility to SSV and HSV. HD cultures showed a depressed replication of both types of HSV. There was a borderline (P = 0.02) correlation between magnitude of HSV replication and presence of HL-A type B-w44, but this does not explain the HD control difference. Furthermore, the level of serum antibodies to HSV common antigen was not related to magnitude of in vitro replication. The results thus speak against generally enhanced cellular susceptibility to HSV as a reason for the high titres of serum antibodies to HSV in HD patients.

Adolescent↗

Cellular and humoral immunity in Hodgkin's disease. I Patients in continuous long-term remission.

Cell-mediated and humoral immunity to herpes simplex virus (HSV), cytomegalovirus (CMV) and varicella zoster virus (VZV) were examined in 37 patients with Hodgkin's disease in continuous long term remission. This group had lower blast-transformation than a matched control group to all 3 antigens. Patients originally showing B-symptoms had higher transformation to VZV than those with A-symptoms. Patients treated with irradiation only had higher transformation than those treated with either chemotherapy or a combination of chemotherapy and irradiation. There was a clear tendency towards lower transformation in patients having been in remission for 2 years or less. Phytohaemagglutinin (PHA) stimulation gave lower response in the patient group than in the control group. Patients with B-symptoms had lower response than those with A-symptoms. Interferon production was specially impaired in patients with B-symptoms. The patient group had higher CF titers against HSV and CMV while the control group had higher titers against VZV. B-symptom patients had higher titers against VZV than A-symptom patients. It is concluded that HD patients have impaired immune function many years after discontinuation of therapy, but there are certain differences regarding the in vitro immunity within the patient groups.

Antibody Formation↗

Abolished production of interferon by leucocytes of patients with the acquired cytogenetic abnormalities 5q -- or -- 5 in secondary and de-novo acute non-lymphocytic leukaemia.

Interferon production by leucocytes on stimulation with inactivated antigens from herpes simplex virus, varicella zoster virus and cytomegalovirus was determined in 19 patients with preleukaemia or acute non-lymphocytic leukaemia, in 15 following treatment for other tumours. Production of interferon was abolished in 10 patients and preserved in nine cases after stimulation with herpes simplex antigen. Cytogenetic studies of bone marrow demonstrated an abnormal karyotype in 13/15 patients with secondary preleukaemia or leukaemia. Characteristics were (a) hypodiploid cell lines demonstrated in eight cases, (b) a B-chromosome defect found in five cases and verified as 5q -- in four, and (c) defects in C-group chromosomes in 10, verified as monosomy 7 in nine. All four patients with de-novo preleukaemia or leukaemia had abnormal cytogenetic findings, two B-chromosome abnormalities verified as monosomy 5. A relationship between abnormalities in chromosome no. 5 and abolished production of interferon was demonstrated, as only one of seven patients with 5q --, --5 or --B produced interferon by the leucocytes, compared with eight of a total of 12 patients with other cytogenetic defects or a normal karyotype (P=0.04). The results are remarkable, as chromosome no. 5 has recently been discovered to contain a gene for interferon production. Furthermore abolished production of interferon by leucocytes seemed correlated to previous irradiation and to disease-related fever.

Acute Disease↗

Cell-mediated and humoral immunity to herpesviruses during and after herpes zoster infections.

The influence of herpes zoster virus infection on cell-mediated and humoral immunity to varicella-zoster virus (VZV), cytomegalovirus, and herpes simplex virus (HSV) was followed in 17 zoster patients from the first week to 6 months after start of eruptions. The clinical responses were registered and correlated to the immune responses. A significant depression in blast transformation on stimulation of lymphocytes with all three antigens was found on days 1 to 5 compared with transformations later after zoster eruptions and compared with controls. Phytohemagglutinin exhibited the same stimulation in the different groups and controls. No significant differences in interferon production in the various groups and controls were found on stimulation with the VZV and HSV antigens. All zoster patients became seropositive by complement fixation to VZV a few days after start of the zoster eruption. Two zoster patients showed a fourfold rise in complement fixation antibodies to HSV. Three patients had changes in complement fixation titers to cytomegalovirus, which could indicate new infection or reactivation of infection with this virus. A significant lower transformation index to VZV was found during the first 9 days in zoster patients with fever compared with patients without fever. The relevance of this observation is discussed in relation to a previous similar observation from our group.

Adult↗

Cell-mediated and humoral immune responses to herpes simplex virus and cytomegalovirus in renal transplant patients.

Cell-mediated immunity to herpes simplex virus and cytomegalovirus, using the lymphocyte transformation test and interferon induction in lymphocytes, was studied in 59 patients from 1 day to 7 years after allotransplantation and compared with the results in normal subjects. Both parameters were permanently depressed with regard to cytomegalovirus. With herpes simplex virus, interferon production was also permanently depressed, whereas the transformation reaction was normal during the first year after transplantation and only slightly depressed in patients more than 1 year after transplantation. In 6 patients the above-mentioned assays and the complement fixation reaction were performed serially and related to the clinical signs of herpes simplex virus and cytomegalovirus infection. The relationship between depression of the transformation reaction and interferon production in lymphocytes and the occurrence of clinically evident herpes simplex virus and cytomegalovirus infections was, however, equivocal. The humoral immune response to herpes simplex virus was measured by the complement fixation test and the more sensitive antibody-dependent, cell-mediated cytotoxicity reaction, and a good correlation was found between these two tests, although only a few persons were found to be negative in the antibody-dependent, cell-mediated cytotoxicity reaction. The suggestion is made that only a few adults are "true" herpes simplex virus seronegative.

Adolescent↗

Pleural effusion disease in rabbits. Interferon in body fluids and tissues after experimental infection.

The distribution of interferon in body fluids and tissues was studied in 18 rabbits infected experimentally with the agent of pleural effusion disease (PED). Circulating interferon of the classical type was demonstrable 12 h after inoculation, and a maximum response was attained 2-3 days later. Circulating interferon disappeared between 6 and 8 days after inoculation. Interferon titres of serum were closely correlated with the early phase of febrile response and probably also with the initial growth phase of the PED agent. The interferon titres of pleural fluid exceeded by far the titres of other body fluids and tissues. No interferon could be demonstrated in brain, liver and urine.

Animals↗

Humoral and cell-mediated immune responses in humans before and after revaccination with vaccinia virus.

Twenty-six healthy males vaccinated 15 to 18 years ago with vaccinia virus were revaccinated. Blood samples were collected before vaccination and 3 weeks after. The lymphocytes were tested in a blast transformation assay with vaccinia antigen and phytohemagglutinin, and interferon production was measured. The sera were subjected to neutralization and antibody-dependent cell-mediated cytotoxicity (ADCC) tests. All results were compared with clinical responses. The only test showing immunity in all donors before vaccination was the ADCC. The other tests showed a very limited residual immunity or no immunity at all. After revaccination, immunity reactions were found in all tests in most of the donors. None of the tests made before vaccination could be used to predict clinical reactions. The ADCC is recommended as a sensitive serological test.

Adult↗

Lymphocyte-mediated cytotoxicity in humans during revaccination with vaccinia virus.

Fifteen healthy human volunteers were revaccinated with vaccinia virus. Blood samples (4 to 7) were obtained during the 3 weeks after revaccination. Peripheral blood lymphocytes were washed extensively and tested for cytotoxicity against vaccinia-infected autologous and/or homologous skin fibroblasts. Without addition of antibodies, peak levels of killing were observed on days 7 to 9. The killing did not depend on common HLA markers. On days with peak activity, extensively washed lymphocytes showed higher levels of killing than normally washed lymphocytes. By cell separation experiments, the cell most active in killing proved to be a nonadherent, non-phagocytizing lymphocyte with Fc receptors. Serum antibodies tested in two sensitive serological assays peaked on days 14 to 17. The question of whether the killing observed is dependent on or independent of antibodies is not clarified in the present study.

Antibody-Dependent Cell Cytotoxicity↗

Cellular and humoral immune responses to herpes simplex virus during and after primary gingivostomatitis.

A total of 17 children, aged 1 to 15 years, with gingivostomatitis were investigated to follow the development of immune parameters in those who suffered from herpes simplex virus stomatitis. Mouth swabs were obtained during the acute attack. Blood samples were collected on this occasion and again about 3 weeks later. Humoral immunity to herpes simplex virus was investigated by a complement fixation test and by an antibody-dependent cell-mediated cytotoxicity test. Cell-mediated immunity was investigated in a blast transformation assay with herpes simplex virus type 1 antigen and phytohemagglutinin. Interferon production in herpes-stimulated cultures was measured. Thirteen patients had a herpes simplex stomatitis. Twelve of these children were negative in the complement fixation test on the first serum specimen, but only five were negative in the antibody-dependent cell-mediated cytotoxicity test. These five were still febrile at the time of investigation. Blast transformation was negative at the first investigation in most children, whereas interferon was produced both in leukocyte cultures obtained during the infection and also in cultures made 3 to 4 weeks after the infection. An increase in immune parameters was seen in all patients with herpes stomatitis. From results in blast transformation and antibody-dependent cell-mediated cytotoxicity, it is seen that cell-mediated and humoral immunity can be found at the same time during recovery from this type of infection.

Adolescent↗

Function of fever in infectious disease.

The survival of fever in infectious disease is a controversial subject. In favour of the hypothesis that the fever response is one of the defence mechanisms of the host aginst micro-organisms are several data ranging from determinations of optimal growth temperatures of micro-organisms in vitro to in vivo experiments on the course of infections in temperature-manipulated warm-blooded and poikilothermic animals. In spite of this, the beneficial effect of an elevated body temperature has only been documented in a few human infections, and antipyretic drugs are still used in enormous quantities in the fight against the symptom "fever", as if this were the enemy.

Animals↗

Function of fever.

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Body Temperature↗

[Interferons].

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Antigens, Viral↗

Cell-mediated cytotoxicity to herpes-infected cells in humans: dependence on antibodies.

Herpes simplex virus type 1 (HSV-1)-infected human skin fibroblasts were used as target cells in a 51Cr release assay, using peripheral blood mononuclear cells from HSV-seropositive and -seronegative donors as effector cells. Cytotoxicity was exerted by ordinarily prepared lymphoid cells but could be reduced by extensive washing of the effector cells. The antibody dependence of the system was shown by the recovery of activity through addition of positive serum or medium used for the early washes of effector cells. Three donors found to be seronegative in the usual serological tests were shown to be seropositive in this test. It is proposed that the assay can be used as a very sensitive serological test.

Antibodies, Viral↗

Use of purified cytomegalovirus as antigen in the complememt fixation test.

Crude cytomegalovirus (CMV) antigen and purified CMV antigen were used in tests for complement-fixating (CF) antibodies in sera from 7 patients with CMV infection. CF antibodies to purified CMV appeared later than the other CF antibodies tested and parallel to neutralizing antibodies.

Antibodies, Viral↗