Biomedical subjects

H Blomgren

Publications and source records attributed to H Blomgren.

At least 55 records · Page 3Linked to original sources

PubMed1988

Synergistic enhancement of mitogen responses of human lymphocytes by inhibitors of cyclo-oxygenase and lipoxygenase.

Previously we reported that inhibitors of the enzyme cyclo-oxygenase, which reduce biosynthesis of prostaglandins, may enhance mitogenic responses of human blood lymphoid cells, whereas only marginal effects were observed with 5,8,11-eicosatriynoic acid (ETI), which inhibits 12-lipoxygenase and leukotriene biosynthesis. However, sharply enhanced mitogen responses were observed when lymphoid cells were cultured with both a cyclo-oxygenase inhibitor and ETI, suggesting a synergy between the two drugs. To test whether this is a more general phenomenon occurring between inhibitors of cyclo-oxygenase and lipoxygenase, we have now extended these studies to include the following lipoxygenase inhibitors: cirsiliol; esculetin; 5,8,11,14-eicosatetraynoic acid, and nordihydroguaiaretic acid. The results have shown that any of these drugs combined with a cyclo-oxygenase inhibitor may enhance mitogen responses more than one would expect by summing the effects of the inhibitors tested separately. We conclude that inhibitors of cyclo-oxygenase and lipoxygenase may synergistically enhance mitogen responses of lymphoid cells.

Arachidonate Lipoxygenases↗

PubMed1988

Modulation of lymphocyte and monocyte responses in vitro by 9-deoxy-delta 9-prostaglandin D2 and 9-deoxy-delta 9-delta 12-prostaglandin D2.

The effects of 9-deoxy-delta 9-prostaglandin D2 (PGJ2) and 9-deoxy-delta 9-delta 12-prostaglandin D2 (delta 12PGJ2), which are metabolites of PGD2, on lymphocyte and monocyte reactions were studied in vitro. Expression of various phenotypic markers of lymphocyte subsets, as detected by monoclonal antibodies, was not affected by overnight incubation in 3 x 10(-5) M PGJ2. Phytohemagglutinin stimulation and natural killer activity of lymphocytes was reduced by PGJ2 and delta 12 PGJ2. Monocyte reactivity to 12-o-tetradecanoylphorbol-13-acetate, as assessed by chemiluminescence, was stimulated by preincubation of the cells for 1 h in 3 x 10(-5) M PGJ2 or delta 12 PGJ2. Such an augmentation was not exerted by PGD2.

Adjuvants, Immunologic↗

PubMed1987

Adjuvant Bestatin immunotherapy in patients with transitional cell carcinoma of the bladder. Clinical results of a randomized trial.

The first clinical results of an ongoing, prospective trial to determine the value of adjuvant Bestatin immunotherapy in the management of bladder cancer are presented. Patients with nonmetastatic transitional cell carcinoma of the bladder, scheduled for full dose local radiation therapy (64 Gy), were randomly allocated to adjuvant oral Bestatin treatment (30 mg daily for at least 1 year), starting at completion of irradiation, or no Bestatin. The longest follow-up period of the 151 evaluable patients is 6 years. The results have shown that the disease-free survival of the patients taking Bestatin is significantly improved compared to the controls (p = 0.04). However, the overall survival of the patients was not affected by the Bestatin treatment. The beneficial effect of Bestatin seemed to be more marked among men than women. Furthermore, statistical analyses of the patient material according to T tumor categories suggested that compared to the controls, patients with less advanced disease (T1 and T2) benefitted more from Bestatin treatment than those with more advanced tumors (T3 and T4). The results of this ongoing trial thus show that patients with bladder cancer benefit from adjuvant Bestatin treatment in terms of disease-free survival.

Adjuvants, Immunologic↗

PubMed1987

Two randomised phase II trials of intermittent intravenous versus subcutaneous alpha-2 interferon alone (trial 1) and in combination with 5-fluorouracil (trial 2) in advanced colorectal cancer.

Sixty-five patients with advanced colorectal cancer were randomised to one of two schedules of recombinant alpha-2 interferon (IFN). In the first study, 36 patients received single-agent IFN, either 50 X 10(6) U/m2 intravenously on 5 consecutive days every 4 weeks, or 20 X 10(6) U/m2 subcutaneously three times per week. No tumour responses were seen and toxicity was unacceptable. In the second study, 29 patients received IFN in two similar schedules, but the dose of IFN was reduced to 20 X 10(6) U/m2 per day in the intravenous arm and to 5 X 10(6) U/m2 per day in the subcutaneous arm. In addition these patients were administered intravenous 5-Fluorouracil (5-FU), 250-500 mg/m2 per day on the first 5 days of each 4-weekly cycle. Although the toxicity of this second study was tolerable, only one short-lived partial remission was observed. Alpha-2 interferon, alone or in combination with 5-FU, is ineffective in advanced colorectal cancer.

Adenocarcinoma↗

PubMed1987

Changes of the blood lymphocyte population following 131I treatment for nodular goiter.

The blood lymphocyte population was examined in 34 patients who were treated with 131I for toxic or atoxic nodular goiter. The patients received one to three doses of 300-550 MBq of 131I administered at 1 week intervals. Lymphocyte counts were significantly reduced both 1 and 6 weeks after treatment. This reduction was accompanied by a changed composition of the lymphocyte population. The frequency of lymphocytes expressing membrane receptors for C'3 (EAC-rosette forming) was significantly reduced 1 and 6 weeks after 131I-administration. At 6 weeks there was a slight but statistically significant increase of the frequency of T-cells as identified by Leu 1 monoclonal antibodies. This was largely caused by an increased proportion of helper/induced T-cells as identified by Leu 3a monoclonals. 131I-treatment also reduced the capacity of lymphocytes to secrete immunoglobulins (Ig) upon PWM-stimulation. The most pronounced effect was observed for IgM. Secretion of IgG and IgA were less reduced. Mitogenic stimulations of lymphocytes with PHA and ConA were not significantly changed. We conclude that these changes observed, with the exception of mitogen reactivity, are essentially similar to those occurring after external radiation therapy for cancer. We speculate that blood lymphocytes passing through the continuously irradiated gland are damaged mainly by emitted beta-particles.

Adult↗

PubMed1987

Effect of 32P treatment for polycythaemia vera on blood lymphocyte subpopulations and their functions.

The influence of 32P treatment on the blood lymphocyte population was examined in 16 patients with polycythaemia vera who had not previously been treated with cytotoxic drugs or irradiation. Before treatment the lymphocyte counts were within the normal range but the expression of certain membrane structures, as detected by monoclonal antibodies directed against total T cells (CD 3 and 5), helper/inducer (CD 4) and suppressor/cytotoxic T cells (CD 8), were slightly reduced. In addition, mitogenic responses of the lymphocytes to PHA and PWM-induced Ig secretion were severely impaired. Following a single oral dose of 32P (150-305 MBq), which was shown to normalize the production of erythrocytes and/or platelets, the blood lymphocyte counts were reduced by approximately 40% 12 wk after treatment. Subset analysis showed that the proportion of B cells, as identified by monoclonal antibodies (CD 20), was reduced to the highest relative extent. On the other hand, lymphocytes expressing the above T cell markers were somewhat increased. 32P treatment sharply increased PHA reactivity but it further reduced PWM-induced Ig secretion. The latter observation was in line with the finding that serum concentrations of Ig were reduced following treatment.

Aged↗

PubMed1987

Synergistic enhancement of mitogen responses of human lymphocytes by inhibitors of cyclo-oxygenase and 5,8,11-eicosatriynoic acid, an inhibitor of 12-lipoxygenase and leukotriene biosynthesis.

Blood mononuclear cells are well-known producers of various cyclo-oxygenase and lipoxygenase metabolites of arachidonic acid, some of which possess immunoregulatory functions. In the present investigation, we have examined 3H-thymidine incorporation in human blood lymphocytes cultured with polyclonal mitogens and antigens in the presence of various inhibitors of cyclo-oxygenase (such as indomethacin and meclofenamic acid) and an inhibitor of 12-lipoxygenase and leukotriene biosynthesis, 5,8,11-eicosatriynoic acid (ETI). It was observed that these inhibitors could augment mitogen responses of nonpurified lymphocyte preparations but not of preparations which were depleted of monocytes. The results indicate that monocytes and not lymphocytes were the main producers of immunosuppressive eicosanoids derived from arachidonic acid. Further, mitogenic responses in the presence of both an inhibitor of cyclo-oxygenase and ETI were augmented to a higher extent than expected. Again, this enhancement was not observed in preparations depleted of monocytes. Arachidonic acid metabolism was examined in mitogen-stimulated cultures pulsed with 14C-arachidonic acid. It was observed that the production of three metabolites was inhibited by meclofenamic acid, whereas the amounts of another 14Cr-labeled compound were almost doubled in the presence of meclofenamic acid.

8,11,14-Eicosatrienoic Acid↗

PubMed1987

Effects of some prostaglandins and leukotrienes on lymphocytes, monocytes and their activity in vitro.

The effect of some prostaglandins (PGs) and leukotrienes (LTs) on lymphocytes and monocytes was tested in vitro. Overnight incubation with PGD2 reduces the expression of Leu-2 antigen (suppressor/cytotoxic phenotype) and of Fc receptors for IgG. PGA2, PGD2 and to a lesser extent PGE2 inhibit PHA reactivity of lymphocytes. LTB4 does not have any inhibitory activity. Preincubation of lymphocytes with PGD2 and PGE2 decreases their NK activity. LTB4, but not the PGs tested, stimulates monocyte metabolism as assessed by chemiluminescence.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1987

Incidence of infectious symptoms after radiation therapy for breast cancer. Long-term effects.

The incidence of symptoms generally associated with infectious disease was assessed by a questionnaire sent out to 519 disease-free breast cancer patients 7 to 12 years after primary treatment. All patients were treated in the context of a randomized trial where pre- and postoperative radiation (45 Gy) was evaluated versus surgery only. The results indicate a significantly higher morbidity among patients treated with preoperative irradiation compared with those irradiated postoperative (p less than 0.05). This increased morbidity mainly seemed to be caused by symptoms usually associated with respiratory tract infection (p less than 0.05). Although statistically not significant the preoperatively irradiated patients also had a higher morbidity than those treated with surgery alone. There was no difference between postoperatively irradiated patients and patients treated with surgery only. A significantly higher integral dose (absorbed energy within the body) of the pre- compared with the postoperative group (p less than 0.025) is associated with the differences in morbidity between the two irradiated groups. An explanation for the increased morbidity seems to be that the volume of lung tissue, encompassed within the full-dose target volume, is the crucial factor. This volume was considerable in the preoperatively treated patients but kept at a minimum in the postoperative group.

Adult↗

PubMed1986

Prognostic relevance of postirradiation lymphocyte reactivity in breast cancer patients.

The prognostic relevance of phytohemagglutinin (PHA) and purified protein derivative (PPD) lymphocyte reactivity at diagnosis and after radiotherapy was evaluated in breast cancer patients. The patients were followed up to 13 years and the prognostic value expressed as ratios between observed number of deaths and "estimated" number of deaths under the null hypothesis. There was no significant association between the initial PHA and PPD reactivity and the survival of the patients. On the other hand, mortality up to 8 years after radiotherapy was significantly higher for patients with low PHA and PPD reactivity at completion of treatment. Furthermore, patients who had higher than average PPD reactivity 6 to 10 months after radiotherapy, seemed to have a higher survival rate. The prognostic relevance of postirradiation lymphocyte reactivity was only to some extent explained by clinical stage.

Breast Neoplasms↗

PubMed1986

Enteral and parenteral nutrition in anorectic patients with advanced gastrointestinal cancer.

Seventeen patients with advanced, noncurable gastrointestinal cancer with symptoms of anorexia and malnutrition were treated with controlled enteral or total parenteral nutrition over a 3-week period. Eleven patients received enteral and six parenteral nutrition. The nutrition was given with 30-40 kcal/kg b.w. daily. No anticancer treatment was given. Before and after the treatment period, the patients were assessed regarding their nutritional, immunological, and performance status. None of the studied nutritional parameters changed significantly over the 3-week period and there was no clear indication of an improved lymphocyte reactivity. There was a tendency toward improvement in performance status for the patients on enteral nutrition, while the reverse seemed to be true for the parenteral group. It is concluded that nutritional support may halt the progressive malnutrition often seen in patients with cancer and serve as a palliative treatment in selected patients.

Aged↗

PubMed1986

Relation between the site of primary intracranial tumors and mitogenic responses of blood lymphocytes.

The possible relation between the site of primary intracranial tumors and mitogenic responses of blood lymphocytes was analyzed in 115 patients who had not undergone surgery or received any radiation or chemotherapy. Some of the patients had however received corticosteroid treatment. PHA responses were impaired in nonsteroid treated patients with tumors affecting the left cerebral hemisphere. They were normal in patients with tumors affecting the right cerebral hemisphere or central structures of the brain or tumors growing in the posterior fossa of the skull. Lymphocyte responses to PPD were normal in patients with hemispheric or posterior fossa tumors. However, the PPD response was sharply reduced in patients with central tumors. The results could not be explained by different histological tumor types or anticonvulsant medication in the various patient groups. In addition, the capacity of sera to promote mitogen stimulation of lymphocytes did not differ significantly between the patient groups. It is speculated that intracranial tumors may interfere with the function of certain centers in the brain which are involved in the regulation of lymphocyte responses.

Adrenal Cortex Hormones↗

PubMed1986

Blood lymphocyte subsets in patients with primary intracranial tumours. Correlation to histological tumour type and anatomical site.

The blood lymphocyte population of 118 patients with primary intracranial tumours and healthy volunteers was examined with respect to its size and cellular composition using various rosette tests. The patients had not undergone any surgical intervention or received any treatment with ionizing irradiation or cytotoxic drugs. However, some of them were treated with corticosteroids. It was observed that non-steroid treated patients with oligodendrogliomas, but not patients with other histological types of tumours, had a significantly reduced proportion of "active" T-lymphocytes forming rosettes with sheep erythrocytes (a type of T-lymphocyte which is activated by foetal calf serum). These patients as well as those with astrocytomas, malignant gliomas (anaplastic astrocytomas and glioblastomas) or miscellaneous tumours (mainly meningiomas) had normal proportions of lymphocytes with receptors for the Fc-part of IgG or C'3 and cells forming rosettes with sheep erythrocytes under more conventional conditions. Patients who were treated with corticosteroids had an increased frequency of lymphocytes with the above Fc-receptor. An association between site of the lesions and cellular composition of the blood lymphocyte population was not detected. The results give further support for the view that the immunological system may be changed in patients with oligodendrogliomas.

Adolescent↗

PubMed1986

Natural killer activity of blood lymphocytes in patients with primary intracranial tumors. Correlation to histological tumor type and anatomical site.

The possible relationship between the natural killer (NK) activity of blood lymphocytes and the histological tumor type or anatomical location of the lesions was examined in 116 patients with primary intracranial tumors. The patients had not undergone any surgical intervention or received any treatment with ionizing radiation or cytotoxic drugs. However, some of them had received corticosteroid medication. Regardless of the histological type of tumor, there was no significant difference in the NK activity of the non-corticosteroid treated patients and the healthy control subjects. However, there was a trend towards an increased NK-activity in patients with low-grade gliomas, in particular oligodendrogliomas. The NK-activity was reduced in patients who were treated with corticosteroids. There was no relationship between the NK-activity in non-steroid treated patients and the anatomical location of the tumor. The latter finding contrasts to a recent observation showing a strong relationship between tumor site and PPD-reactivity of blood lymphocytes in patients with intracranial tumors.

Adult↗

PubMed1986

Prostaglandin sensitivity of the PHA-response of blood lymphocytes following radiation therapy for breast cancer.

The reduction of mitogen responses of blood lymphocytes which occur after radiation therapy for breast cancer, known to be largely due to inhibitory monocytes, can partly be reverted by indomethacin which is an inhibitor of prostaglandin (PG) synthesis. This may indicate that PG-synthesis by blood monocytes is increased after irradiation or that PG-sensitivity of the lymphocyte population is increased. To test the latter possibility the sensitivity of the PHA-response of blood lymphocytes to varying concentrations of PGE2 and PGD2 was examined in 15 patients with breast cancer before and up to 6 months after local radiation therapy (46 Gy). The results showed that the sensitivity of the PHA-response was not significantly changed after treatment suggesting that the immunosuppression observed after irradiation is partly due to an increased production of PGs rather than an increased PG-sensitivity of lymphocytes.

Adult↗

PubMed1986

Long-term effects on the immune system following local radiation therapy for breast cancer. 4. Proliferative responses and induction of suppressor activity of the blood lymphocyte population.

The long-term effect of local irradiation for breast cancer on the blood lymphocyte population was examined in 149 women who had been disease-free for 5-6 and 10-11 years. The patients were included in a clinical trial aiming at determining the value of pre- and post-operative irradiation (45 Gy) compared to surgery only. It was observed that the relative mitogen responses of lymphocytes to phytohaemagglutinin (PHA) and Concanavalin (Con A) and in a mixed lymphocyte culture (MLC) were significantly lower in irradiated compared to unirradiated patients at least a decade after treatment. The prolonged reductions of mitogen responses after irradiation could partly be due to an increased proportion of lymphocytes which may express suppressor function since the Con A-inducible suppressor activity of lymphocytes was significantly higher in irradiated compared to unirradiated patients.

Adult↗

PubMed1986

Stereotactic radiation therapy of intracranial arteriovenous malformations.

Twenty-six patients with large intracranial arteriovenous malformations (AVM), not suited for open surgery or radiosurgery, have been treated by fractionated stereotactic radiation therapy using a linear accelerator. The preliminary results are based on follow-up angiography one and a half years after treatment, and in 5 cases also 5 years after treatment. In 2 cases a complete obliteration of the AVMs has occurred, and in the majority of the remaining cases a reduction of the size of the lesion has been obtained. Further development of the method is needed in order to improve the results. Today treatment with this technique is only recommended in cases which cannot be treated with other methods.

Adolescent↗

PubMed1986

Effect of tamoxifen on pokeweed mitogen stimulated immunoglobulin secretion in vitro.

The influence of Tamoxifen on pokeweed mitogen induced immunoglobulin (Ig) secretion of human blood lymphocytes was tested in vitro. It was observed that pretreatment of T cell enriched preparations with "therapeutic" concentrations of Tamoxifen augmented their capacity to promote IgG but not IgM secretion of untreated autologous B-lymphocytes. Cultures containing Tamoxifen pretreated B cell enriched preparations and untreated T cells exhibited reduced secretion of both IgG and IgM.

Adult↗