Identification and characterization of clonal NK-like cells from channel catfish (Ictalurus punctatus)

TcR alpha, beta, and gamma chain negative cytotoxic NK-like cells were cloned from alloantigen-stimulated PBL obtained from nai;ve channel catfish. Stimulation with allogeneic cells and growth promoting factors are required for their continued in vitro proliferation and cytotoxic activity. These granular cells kill not only the stimulating allogeneic cells, but also unrelated allogeneic targets by a perforin/granzyme-mediated apoptosis pathway. In addition, they are negative for markers that define neutrophils, monocytes/macrophages, and non-specific cytotoxic cells. Although these NK-like clones kill a number of different allogeneic targets, they display interclonal variation in cytotoxicity toward a panel of allogeneic targets, i.e. some clones have no apparent target specificity, while others display a target preference. In addition, flow cytometric analyses revealed that expression of a putative FcmuR, an LFA-1-like molecule, and a putative thymocyte/T cell antigen varies among the different clones, with no clear correlation between surface antigen expression and cytotoxic activity. Although not all clones express a putative FcmuR, it was noted that they all expressed an ITAM containing FcepsilonR gamma chain homolog. This finding suggests that the catfish FcepsilonR gamma chain may potentially be used as an accessory molecule for not only FcmuRs, but also for other unknown activation receptors. These results support the hypothesis that catfish NK-like cells are heterogeneous in terms of target specificities and cell surface phenotype.     

Evaluation of dose-response models and parameters predicting radiation induced pneumonitis using clinical data from breast cancer radiotherapy

The purpose of this work is to evaluate the predictive strength of the relative seriality, parallel and LKB normal tissue complication probability (NTCP) models regarding the incidence of radiation pneumonitis, in a large group of patients following breast cancer radiotherapy, and furthermore, to illustrate statistical methods for examining whether certain published radiobiological parameters are compatible with a clinical treatment methodology and patient group characteristics. The study is based on 150 consecutive patients who received radiation therapy for breast cancer. For each patient, the 3D dose distribution delivered to lung and the clinical treatment outcome were available. Clinical symptoms and radiological findings, along with a patient questionnaire, were used to assess the manifestation of radiation-induced complications. Using this material, different methods of estimating the likelihood of radiation effects were evaluated. This was attempted by analysing patient data based on their full dose distributions and associating the calculated complication rates with the clinical follow-up records. Additionally, the need for an update of the criteria that are being used in the current clinical practice was also examined. The patient material was selected without any conscious bias regarding the radiotherapy treatment technique used. The treatment data of each patient were applied to the relative seriality, LKB and parallel NTCP models, using published parameter sets. Of the 150 patients, 15 experienced radiation-induced pneumonitis (grade 2) according to the radiation pneumonitis scoring criteria used. Of the NTCP models examined, the relative seriality model was able to predict the incidence of radiation pneumonitis with acceptable accuracy, although radiation pneumonitis was developed by only a few patients. In the case of modern breast radiotherapy, radiobiological modelling appears to be very sensitive to model and parameter selection giving clinically acceptable results in certain cases selectively (relative seriality model with Seppenwoolde et al and Gagliardi et al parameter sets). The use of published parameters should be considered as safe only after their examination using local clinical data. The variation of inter-patient radiosensitivity seems to play a significant role in the prediction of such low incidence rate complications. Scoring grades were combined to give stronger evidence of radiation pneumonitis since their differences could not be strictly associated with dose. This obviously reveals a weakness of the scoring related to this endpoint, and implies that the probability of radiation pneumonitis induction may be too low to be statistically analysed with high accuracy, at least with the latest advances of dose delivery in breast radiotherapy.     

Tacrine restores cholinergic nicotinic receptors and glucose metabolism in alzheimer patients as visualized by positron emission tomography

Three patients with Alzheimer's disease, a 68-year-old woman with mild dementia and 2 men (aged 64 and 72 years) with moderate dementia were treated orally with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine), 80 mg daily, for several months. The patients were investigated using positron emission tomography (PET) prior to, and after 3 weeks and 3 months of treatment. The PET studies involved a multi-tracer system consisting of [¹⁸F]-fluoro-deoxy-glucose (¹⁸F-FDG) (tracer for glucose metabolism); ¹¹C-butanol (cerebral blood flow) and (S)(−)- and (R)(+)-[N-¹¹C-methyl]-nicotine (nicotinic receptors; cholinergic neural activity). Tacrine treatment increased the uptake of ¹¹C-nicotine to the brain. Significant reduced difference in uptake between the two enantiomers (S)(−)- and (R)(+)¹¹C-nicotine was observed in the frontal and temporal cortices after tacrine treatment in all three patients. The kinetic analysis indicated increased binding of (S)(−)¹¹C-nicotine in brain compatible with a restoration of nicotinic cholinergic receptors. The most pronounced effect was observed after 3 weeks and 3 months treatment in the patient with mild dementia. An increase in cerebral glucose utilization was found in the 68-year-old patient with mild dementia but also slightly in the 64-year-old man with moderate dementia when treated with tacrine for 3 months. Tacrine administration did not affect cerebral blood flow. The PET data obtained after 3 weeks of tacrine treatment was paralleled by improvement in neuropsychological performance. This study shows in vivo by PET neurochemical effects induced in brain by treatment with tacrine to Alzheimer patients. Intervention with tacrine in the early course of the disease might be necessary for clinical improvement.     

Differential effects of cancer rehabilitation depending on diagnosis and patients' cognitive coping style

OBJECTIVE: The major aim was to explore the extent to which the Miller Behavioral Style Scale (MBSS) can be used to differentiate cancer patients who are likely to benefit from rehabilitation efforts with a strong information component from those who are not. METHODS: Newly diagnosed patients with breast, gastrointestinal, or prostate cancer (N = 442) were included in a randomized, prospective study of the effects (on anxiety, depression, intrusion, avoidance) of rehabilitation approximately 4 months after diagnosis as compared with control patients. Patients were classified as "monitors" or "blunters" on the basis of the MBSS (368 patients, 83%, completed the MBSS). RESULTS: The expected interaction at postintervention between coping style and experimental condition (ie, rehabilitation or control) was found only for avoidance among breast and prostate cancer patients. Assignment to the rehabilitation or control condition was of no importance for outcome among blunters. Among monitors, the response pattern differed between breast and prostate cancer patients. Prostate cancer monitors seemed to benefit from rehabilitation on all outcome measures, whereas intrusion and avoidance were reduced among breast cancer patients in the control condition. This interaction of diagnosis with condition (rehabilitation or control) among monitors is suggested to be due to demands for diagnosis-specific information during diagnostic work, in the period just after diagnosis, and before treatment decision. CONCLUSIONS: Only the monitor concept seems useful for predicting response to cancer rehabilitation with a strong information component. However, whether rehabilitation is of benefit depends also on other factors.     

The intrapulmonary arterial pattern in infants with transposition of the great arteries associated with interventricular septum defect

Summary Microangiographic and histological studies, including serial sectioning, were carried out on the lungs of seven autopsy cases of transposition of the great arteries associated with interventricular septum defect. In five of the cases other cardiovascular abnormalities were also present — valvular pulmonary stenosis, pulmonary and systemic venous anomalies, atrial septal defect and coarctation of the aorta. The ages of the subjects varied from four days to 11 months. Tortuosity of the intralobular pulmonary arteries was observed in three subjects. The number, size and course of the pulmobronchial arteries were normal. A few arterial bronchopulmonary anastomoses (diameter range 50–350 µ) were demonstrated in two subjects. The diameter range of the main bronchial arteries in the aorta-injected specimens was within normal limits. The number of bronchopulmonary arteries was moderately increased in two of the older subjects. The systemic-artery supply of the pulmonary parenchyma, however, was not as prominent as in infants of the same age with isolated transposition of the great arteries.

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Das intrapulmonale, arterielle Gefäßmuster bei Kindern mit Transposition der großen Arterien und Ventrikelseptumdefekt

Zusammenfassung Bei 7 Obduktionsfällen mit Transposition der großen Arterien und Ventrikelseptumdefekt wurden mikroangiographische und histologische Untersuchungen (einschl. Serienschnittstudien) der Lunge durchgeführt. Bei 5 Fällen lagen auch andere kardiovaskuläre Mißbildungen vor: Pulmonalklappenstenose, Venenanomalien, Vorhofseptumdefekte und Coarctatio aortae. Das Alter der Fälle betrug 4 Tage bis 11 Monate. Abnorm gewundene intralobuläre Pulmonalarterienäste wurden bei 3 Fällen beobachtet. Pulmobronchialarterien kamen in normaler Anzahl vor und zeigten keine Abweichungen hinsichtlich Größe oder Verlauf. Eine geringere Anzahl arterieller, bronchopulmonaler Anastomosen (Lumen 50–350 µ) wurde bei 2 der untersuchten Fälle beobachtet. Das Lumen der Hauptäste der Bronchialarterien war normal. Bei 2 der älteren Fälle war die Zahl der Bronchopulmonalarterien mäßig erhöht. Die Bronchialarterien des Lungenparenchyms zeigten jedoch keine so starke Vergrößerung und reiche Verästelung wie bei gleichaltrigen Fällen mit isolierter Transposition der großen Arterien.

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This investigation has been supported by grants from the Swedish National Association against Heart and Chest Diseases, Karolinska Institutes Reservationsanslag, Carin Tryggers fond, and Stiftelsen Therese och Johan Anderssons Minne.     

Changes in the peripheral blood T-Cell receptor V beta repertoire in vivo and in vitro during shigellosis.

A sequential activation of T cells in peripheral blood during shigello sis has been observer (D. Islam, P.K. Bradham, A. A. Lindberg, and B. Christensson, Infect. Immun 63:2941-2949, 1995). To further investigate the cellular response during the course of Shigella infection, changes in the T-cell receptor (TCR) repertoire in the subsets in blood in patients during shigellosis was that Shigella antigens may modulate the function of T cells carrying TCRs capable of recognizing Shigella-specific epitopes or superantigens. Such a selective preference for T cells expressing certain TCR Vbeta types could lead to the expansion or deletion of these T cells. In the present study of 27 adult male Bangladeshi patients with dysentery (14 cases caused by Shigella Dysenteriae 1 and 13 cases caused by Shigella flexneri), the changes in the TCR Vbeta repertoire of peripheral blood CD4+ and CD8+ T-cell subsets have been analyzed with a panel of nine anti-Vbeta monoclonal antibodies by flow cytometry. Twenty healthy males from Bangladesh and 20 healthy males from Sweden served as controls. Compared with the Bangladeshi controls, the patients had an increased frequency of CD4+T cells expression Vbeta2, Vbeta3, and Vbeta17, with a maximum at day 7 after the onset of disease. The frequency of CD4+T cells expressing Vbeta5.1 was increased only in patients with S. flexneri infection. Peripheral blood T cells from Shigella-infected patients also responded to in vitro stimulation in a TCR Vbeta-specific manner. Stimulation with heat-killed S. dysenteriae 1 and Shiga toxin enhanced the frequency of cells expressing Vbeta2, Vbeta3, Vbeta5.1, Vbeta13.6, and Vbeta17, especially in samples obtained at day 7. The enhanced frequency of cells expressing Vbeta2, Vbeta3, Vbeta5.1, and Vbeta17 found both in in vivo and in vitro could suggest that in shigellosis antigens or superantigens are presented to the immune system and preferentially activate certain TCR Vbeta types in T-cell subsets. The kinetics of the change in the TCR Vbeta repertoire in blood during shigellosis may indicate that following local activation, the antigen activated T cells can be retrieved in the blood and restimulated in vitro. If confirmed by parallel analysis of T cells in the gut and blood by TCR sequence analysis, the possibility suggested by our findings would facilitate further analysis of the role of cell-mediated immune responses in the pathogenesis of and protection against Shigella infection.     

Lactate dehydrogenase activity and isoform distribution in normal and hypertrophic smooth muscle tissue from the rat

The lactate dehydrogenase (LDH) activity and isoform distribution of LDH were investigated in tissue samples from the rat portal vein, aorta and urinary bladder. In addition, samples were obtained from hypertrophic urinary bladder. The total LDH activity per unit smooth muscle volume was higher in the urinary bladder compared to that in portal vein and aorta. Five LDH isoforms, reflecting different combinations of the two polypeptide chains denoted H and M, could be separated by agarose gel electrophoresis. The aorta contained more of the H form compared to the portal vein and urinary bladder. This difference suggests that the aorta, which is a slow smooth muscle, is more adapted for aerobic metabolism than the faster muscles of portal vein and urinary bladder. In the hypertrophic urinary bladder a shift in LDH isoform pattern towards less of the H form was found, which correlates with a better maintenance of contraction in anoxia in this type of hypertrophic smooth muscle.