[The role of radiobiology in radiotherapy].
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Biomedical subjects
Publications and source records attributed to K Sakamoto.
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It is known from previous studies that fibers originating from cells in area 2 of the cat primary somatosensory cortex project topographically to area 4 of the motor cortex and that they terminate preferentially in the caudal region of the cruciate sulcus. We examined this pathway to determine more precisely the distribution pattern of fibers and the laminar arrangement of axon terminals in the motor cortex. The recently developed technique of PHA-L staining enabled us to label anterogradely the axons that form this projection. Iontophoretic injections of PHA-L were made into the rostral bank of the ansate sulcus (area 2). After 7 days the cats were perfused and the tissue was processed immunohistochemically to stain the PHA-L filled fibers. Light microscopic examination revealed that a small cluster of cells in the sensory cortex gave rise to multiple foci of labeled axons in area 4. The labeled fibers formed columnlike arrays, which were located for the most part in the posterior bank of the cruciate sulcus and were separated by irregular intervals of cortex devoid of labeled fibers. Clusters of labeled fibers were also found in the anterior region of the cruciate sulcus in some of the animals. The dimensions of the labeled areas and the small number of cells that gave rise to each group of fibers suggested that axonal branches of cells within the injection site formed the multiple foci. Variations in the immunohistochemical staining enabled us to study the laminar distribution of sensory cortex axon terminals with the electron microscope. Whereas some PHA-L labeled terminals were found in the deep cortical layers, the majority (82%) were spread throughout layers I-III. Differences in the laminar distribution of sensory cortex afferents that formed axodendritic or axospinous synapses were noted. Synapses formed with dendritic shafts were relatively sparse (28%) and were confined to the superficial layers. Some of the more numerous axospinous synapses, which accounted for 72% of identified synapses, were found in layers V and VI, although most were in layers I-III. The distribution pattern of terminals showed little variation between columns in different areas of the motor cortex, including that in the anterior cruciate region. The pattern of termination of the sensory to motor cortex projection is discussed in relation to the physiological characteristics of this pathway.
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The present study investigated the role of antigen-presenting cells (APC) in the activation of noncytolytic T cells against tumor antigens. The noncytolytic-type T cells exerted their antitumor effect by producing gamma-interferon (IFN-gamma) and by activating macrophages as the ultimate effectors. The production of IFN-gamma by these noncytolytic T cells following the stimulation with tumor cells required the participation of Ia+ APC, since the depletion of APC from cultures of tumor-immunized spleen cells resulted in almost complete inhibition of the IFN-gamma production. Both L3T4+ and Lyt-2+ subsets of T cells were capable of producing IFN-gamma, and the requirement of APC for the production of IFN-gamma was the case irrespective of whether noncytolytic T cells were of L3T4+ or Lyt-2+ phenotype. More importantly, it was demonstrated that the production of IFN-gamma by L3T4+ and Lyt-2+ T cells was inhibited by addition of the respective anti-class II and anti-class I H-2 antibody to cultures. These results indicate that antitumor L3T4+ or Lyt-2+ noncytolytic T cells are activated for the IFN-gamma production by recognizing tumor antigens in the context of self-class II or -class I H-2 molecules on APC.
To clarify the antigen specificities of autoantibodies in sera and blister fluids from patients diagnosed as bullous pemphigoid (BP) by routine histology and immunofluorescence (IF) methods, indirect IF studies using the salt split-skin technique were performed. In addition, to detect the BP antigen(s) in human epidermal extracts, Western immunoblotting analyses were carried out. Of 41 sera, 39 (95%) showed a linear pattern of fluorescence along the epidermal side of the separation. Two (5%) sera showed a linear pattern of fluorescence along the dermal side. Blister fluids produced IF staining patterns identical with those of serum samples. These fluorescence patterns were not related to the BP antigen expression of the skin used as substrates. In Western immunoblotting analyses, selected sera showing an epidermal pattern on separated skin primarily reacted with 240 kD, 220 kD, 180 kD, and 150 kD proteins extracted from normal human epidermis. Two sera showing a dermal pattern on separated skin revealed no specific bands. The protein bands recognized by blister fluids were identical with those of serum samples. These results indicated that blister fluids are also available in immunological analysis, and that BP antibodies have more than one antigenic specificity. Moreover, it is suggested that differential diagnosis between BP and other bullous diseases may be more important than previously recognized, particularly in patients with epidermolysis bullosa acquisita (EBA).
The generating capacity of interleukin 1 (IL-1) and interleukin 2 (IL-2) by peripheral blood mononuclear cells (PBMNC) was measured in 40 patients with digestive cancer (20 localized and 20 disseminated) and 20 age- and sex-matched control subjects. The localized carcinoma patients showed normal IL-1 production and a significantly depressed IL-2 production (p less than 0.05) when compared to the healthy individuals. The disseminated carcinoma patients exhibited a significant impairment of both IL-1 and IL-2 production in comparison with the healthy controls (IL-1: p less than 0.001, IL-2: p less than 0.001) and the localized carcinoma patients (IL-1: p less than 0.001, IL-2: p less than 0.001). A significant correlation was observed between IL-1 and IL-2 generation in all the cancer patients (r = 0.458, p less than 0.01). These results suggest that progressive tumor growth may result in decreased interleukin production by the host PBMNC, and that related mechanisms, which are more susceptible to lymphocytes than monocytes, may be involved in the impairment of both IL-1 and IL-2 production.
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Mobile chest radiographs obtained in the intensive care unit with a computed radiography system (one of the digital radiography systems) and a conventional screen-film technique were initially compared in 54 pairs. Features such as the air spaces and interstitium of the lungs, the mediastinum, pulmonary vessels, the tracheobronchial tree, and catheters and other devices were compared in both methods. The computed radiography system demonstrated good visualisation of the mediastinum, pulmonary vessels, the tracheobronchial tree, catheters and other devices. Automatic adjustment of the sensitivity and the wide dynamic range of this system were thought to be responsible for the decrease in the number of retakes even in patients with massive fluid collections. The few artefacts created by digital processing were mostly overcome by a routine use of simultaneous display of two different types of image processing.
We investigated the attitudes of parents toward their epileptic children with the "Taken" diagnostic test for child-parent relationships. Included were 70 epileptic children, 31 boys and 39 girls, and their parents, 16 fathers and 59 mothers. Patients were divided into group A, 35 children without neurologic complications other than seizures, and group B, 35 children with complications. The results were evaluated by comparing with the normal standard revised by Akasaka et al. The parents of group A and the fathers of group B showed rejection toward their children. The mothers of group B showed attitudes of dotage and anxiety, especially when their children were over 12 years of age and the seizures were not controlled. Our observations suggest that mental health care for the parents of epileptic children is necessary to decrease the psychological conflicts and to prevent untoward effects on their offspring.
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Plasma renin activity (PRA) was determined in a group of 610 Japanese schoolchildren aged 10-14 years in order to investigate the relationship between PRA distribution and a family history of hypertension. Plasma renin activity was higher in the subjects with a family history of hypertension (FH+) than in those without a family history of hypertension (FH-). Systolic blood pressure (SBP) was also higher in the FH+ group than in the FH- group. The FH- group showed a significant negative correlation between PRA and SBP (boys, r = -0.254, P less than 0.01; girls, r = -0.225, P less than 0.01), whereas the FH+ group showed no correlation between PRA and blood pressure. These results suggested that schoolchildren with a family history of hypertension might have an enhanced renin-aldosterone (R-A) system, resulting in elevation of blood pressure.
Procedures for successful autologous and MHC-matched allogeneic bone marrow transplantation in partially inbred, MHC-defined miniature swine have been established. All marrow recipients were conditioned with single-dose total-body irradiation at the upper level of tolerance, and supported with antibiotics and irradiated blood products during aplasia. Surgical harvest of autologous and allogeneic marrow yielded sufficient numbers of cells to successfully reconstitute recipients. Radiation control animals that received no marrow failed to show recovery of marrow function. Pigs transplanted with autologous marrow at doses greater than 10(8) cells/kg routinely engrafted and recovered normal marrow function. The major clinical complications were acute and chronic infections and hemorrhage. T cell-depleted autologous marrow also engrafted, and there was no observed increase in clinical complications. In bone marrow transplantation across non-MHC allogeneic differences, engraftment and survival were similar to that observed for autologous transplants. The T cell depletion of marrow in such MHC-matched allogeneic recipients was associated in one animal, however, with early reconstitution by cells of autologous origin.
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SSA/Ro antigen is a soluble cellular component to which antibodies are frequently produced in patients with Sjögren's syndrome and systemic lupus erythematosus. Its exact location within the cell has yet to be determined. In this study we report the expression of SSA/Ro antigen in simian virus 40 (SV40)-transformed keratinocytes. The locations of SSA/Ro, U1RNP, and DNA antigens were studied by indirect immunofluorescence using monospecific antibodies. SSA/Ro antigen was detected in both the nucleus and cytoplasm of SV40-transformed keratinocytes tested with three monospecific sera. Primary cultured keratinocytes derived from adult human skin showed localized immunofluorescent staining within the nucleus. When Ca++ concentration of the medium was switched to 0.05 mM, these cells expressed cytoplasmic SSA/Ro antigens within 48 h. Depletion of the antibody activity with insolubilized human spleen extract abolished the staining. Surface expression of this antigen could not be detected in either primary or transformed cells. Localization of U1RNP and DNA was not altered. These results indicate that expression of SSA/Ro antigen in human keratinocytes is modulated by SV40 infection and that this antigen is expressed to a greater degree in cells that are less differentiated, transformed, or proliferating.
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The present study reexamines the cell surface nature of T cells mediating in vivo protective tumor immunity with the use of anti-L3T4 and -Lyt-2 antibodies. C3H/HeN mice hyperimmune against syngeneic MH134 hepatoma or MCH-l-Al fibrosarcoma were prepared by intradermal (id) inoculation of viable tumor cells followed by surgical resection of the tumor and by repeated challenges with viable tumor cells. Spleen cells from these mice were fractionated into L3T4+ or Lyt-2+ T cell subset by treatment with anti-Lyt-2 or -L3T4 antibody plus complement (C). Winn assays performed by utilizing such fractionated T cells have revealed that both L3T4+ and Lyt-2+ T cell subsets from hyperimmune mice produced complete tumor protection. Flow microfluorometry study illustrated that the treatment with anti-L3T4 or -Lyt-2 antibody plus C resulted in the complete isolation of L3T4- Lyt-2+ (Lyt-2+) or L3T4+ Lyt-2- (L3T4+) T cell subset, respectively. This contrasted with the failure of treatment with anti-Lyt-1 antibody plus C to isolate all T cells expressing Lyt-2 marker. It was further demonstrated that each subset of T cells exerted its anti-tumor effect in a tumor-specific way and without a requirement for the other alternative subpopulation of unprimed T cells. These results indicate that Lyt-2+ T cell subset can be successfully isolated by treatment with anti-L3T4 but not with anti-Lyt-1 antibody plus C, and that each single subset of Lyt-2+ and L3T4+ T cells can function as in vivo effector T cells.
The mode of anti-tumor function in vivo of noncytolytic Lyt-2+ T cells from C3H/He mice hyperimmune to syngeneic MH134 hepatoma was investigated in a double diffusion chamber system which was recently established in our laboratory. C3H/He mice were implanted intraperitoneally with the double diffusion chamber unit in which each chamber contained either L3T4+ T cell-depleted MH134-hyperimmune spleen cells plus mitomycin C-treated MH134 tumor cells or other syngeneic X5563 viable tumor cells plus normal spleen cells as a source of macrophages. Inclusion of anti-MH134 Lyt-2+ T cells together with MH134 tumor cells in one chamber resulted in comparable growth inhibition of viable X5563 tumor cells in the other chamber to that obtained by unfractionated MH134-hyperimmune spleen cells. The induction in the Lyt-2+ T cell-containing chamber of anti-tumor effect to be delivered into the other chamber was dependent on the co-existence of Ia-positive adherent cells along with Lyt-2+ T cells. Although adherent cell-depleted Lyt-2+ T cells regained the inducibility of anti-tumor immunity when supplemented with splenic adherent cells, the addition of adherent cells pretreated with chloroquine failed to restore the ability of Lyt-2+ T cells to induce their anti-tumor effect. In addition, paraformaldehyde-treated MH134 tumor cells instead of untreated tumor cells were not capable of activating Lyt-2+ T cells. These results indicate that a portion of Lyt-2+ T cells exerts their anti-tumor effect by a mechanism distinct from direct tumor cell lysis and that their activation for mediation of this type of tumor immunity requires the recognition of tumor antigens processed and presented by Ia-positive adherent cells.