Search PubMed⌕ Search

Biomedical subjects

A Bakke

Publications and source records attributed to A Bakke.

At least 55 records · Page 3Linked to original sources

Natural killer (NK) cell immunodeficiency in patients with chronic myelogenous leukemia. II. Successful cloning and amplification of natural killer cells.

Defective natural killer (NK) cell populations from patients with chronic myelogenous leukemia (CML), that reacted with both HNK-1+ and B73.1+ antibodies, were obtained by a fluorescence-activated cell sorter (FACS). These fractions, along with NK fractions from normal donors which reacted with both antibodies, were expanded as bulk cultures or clones by limiting dilution, for 4 weeks in the presence of 10% interleukin 2 (IL 2), human type AB plasma, and irradiated human allogeneic mononuclear cells. Successfully established clones from patients with CML, with lytic activity against autologous and more differentiated neoplastic granulocytes, were generated more efficiently from B73.1+ than from HNK-1+ subsets. However, there were no significant differences among the generations of B73.1+ and HNK-1+ clones for both patients and normal donors with lytic activity against NK susceptible K-562 targets. Fresh myeloblast preparations from a blast crisis were found to be more susceptible to lysis by IL 2-proliferative B73.1+ and HNK-1+ clones than were fresh myelocyte preparations from a chronic phase CML patient, which were lytically susceptible to only B73.1+ clones. B73.1+ and HNK-1+ subsets from CML patients demonstrated major histocompatibility complex nonrestricted killing, and showed the following predominant phenotypes: B73.1+T3+T8+ or B73.1+T3+T8- from B73.1+ subsets; and HNK-1-T3+T8+ (initially HNK-1+) from HNK-1+ subsets. In contrast, B73.1+ and HNK-1+ clones from normal donors showed the following predominant phenotypes: B73.1+T3-T8-; and HNK-1-T3-T8- or HNK-1-T3-T8+ (initially all HNK-1+). Short-term in vitro IL 2 or interferon treatment of fresh NK defective subsets from CML patients resulted in minimal cytotoxic augmentation. In contrast, defective NK cells from CML patients, whether HNK-1+ or B73.1+ subsets, proliferated with complete regeneration of cytolytic activity after a 3-4 week exposure to IL 2, but differed in phenotypic profiles as compared to those of normal donors. These observations imply that not only fresh defective NK cells but also the cytotoxically restored clones from CML patients are derived from different NK subsets and may represent undifferentiated forms of NK cells that may be arrested at an early stage of development by yet unknown mechanism(s). In vitro substantiation of autologous leukemia cell killing by IL 2-proliferative NK cell clones is encouraging and may allow for new in vivo immunotherapeutic modalities in CML patients.

Antibodies, Monoclonal↗

Natural killer-cell immunodeficiency in patients with chronic myelogenous leukemia. I. Analysis of the defect using the monoclonal antibodies HNK-1 (LEU-7) and B73.1.

Quantitative evaluation of natural killer (NK) cells using the HNK-1 (Leu-7) and B73.1 monoclonal antibodies (MAbs) was correlated with NK activity in 13 patients with chronic myelogenous leukemia (CML) and compared to normal donor controls. A consistent observation was the presence of normal absolute numbers of B73.1+ lymphocytes as well as normal to increased absolute numbers of HNK-1+ lymphoid cells in the peripheral blood of chronic-phase CML patients. Despite normal to increased numbers of B73.1+ and HNK-1+ lymphoid cells, these patients consistently demonstrated a significant impairment of lymphocyte-mediated NK activity in their peripheral blood. Further experiments demonstrated that chronic-phase CML patients, in contrast to normal controls, had significantly increased percentages of HNK-1+, E+ and B73.1+, E+ lymphoid cells and significantly decreased percentages of HNK-1+, E- and B73.1, E- lymphoid cells, which resulted in significant reversals of the HNK-1+, E+ to HNK-1+, E- and B73.1+, E+ to B73.1+, E- lymphoid cell ratios. (HNK-1+ [E+/E-] greater than B73.1+ [E+/E-]). Furthermore, as compared to normals, both FACS-sorted HNK-1+ and B73.1+ lymphoid cells from the E+ fraction of CML patients were consistently defective in NK activity, and could not be substantially augmented with alpha-interferon preparations. Although markedly defective in their ability to lyse K-562, HNK-1+ lymphoid cells from the E+ fraction of CML patients were not defective in their ability to bind to the NK-sensitive target, K-562. In contrast, NK-defective B73.1+ lymphoid cells were partially defective in their ability to bind to K-562.

Antibodies, Monoclonal↗

Increased T-helper lymphocytes following active specific intralymphatic immunotherapy of cancer.

Sixteen malignant cancer patients (seven melanoma, three colon, three lung, and three other) who received tumor vaccine therapy--14 autologous and two allogeneic--were studied for T-cell phenotyping changes. Blood samples were obtained prior to therapy, and also at various time intervals following the therapy. A consistent and reproducible elevation of T3 and T4 subsets, as tested on day 21 after the therapy, was observed in 12 patients. The mean percentages of T3 and T4 fractions before and after (21 days) the treatment were 63.8 versus 75.9% (p less than 0.002) and 44.4 versus 57.4% (p less than 0.001), respectively. Kinetic studies of absolute values of three melanoma patients also showed augmentation of T3 and T4 cells following each tumor vaccine. The lymphatic infusion of tumor vaccine did not cause any toxicity, particularly lymphadenopathy. We believe this is the first report demonstrating augmentation of T4 (helper/inducer) cells with tumor cell vaccine therapy.

Female↗

Renal malignancies: outcome of patients in stage 4 with or without embolization procedure.

During four and one-half years a total of 44 patients with renal cell carcinoma in Stage 4 were admitted to our hospital. Of these, 18 patients were treated with an embolization procedure, 8 patients had nephrectomy without embolization, and another 18 patients received no active treatment. Except for the treatment there were no differences between these groups. The survival time was equal whether or not the patients underwent an angioinfarction procedure. We conclude that the embolization procedure has no beneficial effect in itself in these patients.

Aged↗

Screening for hematuria, glucosuria and proteinuria in people aged 55-64. Technical, clinical and cost-benefit experience from a pilot study.

A total of 754 persons randomly selected from the age group 55-64 years were invited by letter to take part in a screening for hematuria, proteinuria and glucosuria. Each person was asked to provide one sample of morning urine and immediately mail it to the laboratory. A total of 413 persons (55%) responded. Two dipsticks: BM-Test-5L and a new single strip for hematuria determination preliminary named BM 33075 were used, both manufactured by Boehringer Mannheim GmbH. The test strips gave positive reaction for hematuria in 21 persons (5.1%), for proteinuria in 14 persons (3.4%), and for glucosuria in six persons (1.5%). All persons with positive tests were invited to follow-up investigations. In the hematuria group we found one person with a malignant disease, 13 with benign conditions and in seven persons we found no reason for the hematuria. Among those with proteinuria one person had a nephritis. Four persons with glucosuria knew about their diabetes mellitus. The cost of the screening was NOK 99 per participant.

Cost-Benefit Analysis↗

Blood hormone levels related to stages and grades of prostatic cancer.

Human follicle stimulating hormone (FSH), human luteinizing hormone (LH), human prolactin, testosterone, estradiol, and sex hormone binding globulin (SHBG) were measured in the blood of 100 consecutive new patients with prostatic carcinoma. According to the VACURG classification, 14% of the patients were in Stage I, 25% in Stage II, 25% in Stage III, and 36% in Stage IV. Within each stage the tumors were further subdivided into either highly, moderately, or poorly differentiated carcinomas. Thus the whole group consisted of 12 categories (stages and grades) of prostatic carcinoma. No specific hormonal pattern emerged which could distinguish any particular category or group of categories. We, therefore, conclude that single hormone measurements are of no practical value for diagnostic purposes related to staging and grading of prostatic carcinoma.

Aged↗

Augmentation of natural killer cell activity after arterial embolization of renal carcinomas.

Preoperative embolization of the renal artery has been reported to improve the survival of patients with advanced renal carcinomas compared to operative treatment only. To investigate possible immunological consequences of tumor embolization, natural killer (NK) cell activity in peripheral blood was investigated immediately before and at different time intervals after occlusion of the renal artery by insertion of a metal coil. A slight increase in NK activity could be observed 24 hr postembolization while a marked augmentation was seen after 48 hr. The high NK activity persisted up to 96 hr after embolization, the last time period included in the study. Two patients undergoing the same procedure but in whom embolization was unsuccessful showed no alteration in NK activity. It is suggested that interferon produced by macrophages activated by the necrotizing tumor might be responsible for the augmentation of NK activity.

Aged↗

The significance of gastric mucosal blood flow and acid secretion in erosive gastritis following hemorrhagic shock in cats.

Gastric acid secretion was stimulated in 21 anesthetized cats by infusion of pentagastrin for 45 min. Thirty minutes later the arterial blood pressure in two groups of the cats was lowered by bleeding to 75 mmHg for two hours, during which time one group was infused with cimetidine and the other with Ringer's solution. The tapped blood was then reinfused and normotension was maintained for two hours. In the third group the cats received pentagastrin and Ringer's solution but were kept normotensive throughout the experimental period. Blood flow was determined with the microsphere distribution technique. The volume and pH of the gastric juice were measured. In the cats with hemorrhagic hypotension, mucosal erosions developd in the corpus/fundus and antrum regions irrespective of cimetidine administration. In the normotensive cats there were few erosions. The gastric mucosal blood flow decreased markedly when the arterial pressure was lowered and returned to control levels and reinfusion of blood. The volume of gastric juice was fairly constant in the experimental period, but the concentration of H+ showed a gradual fall in the three test groups. The study showed that gastric mucosal erosions may develope in cats subjected to hemorrhagic hypotension when the stomach contains gastric acid without bile.

Animals↗