Search for a light pseudoscalar particle in the decay K_{L};{0}-->pi;{0}pi;{0}X.

We performed a search for a light pseudoscalar particle X in the decay K_{L};{0}-->pi;{0}pi;{0}X, X-->gammagamma with the E391a detector at KEK. Such a particle with a mass of 214.3 MeV/c;{2} was suggested by the HyperCP experiment. We found no evidence for X and set an upper limit on the product branching ratio for K_{L};{0}-->pi;{0}pi;{0}X, X-->gammagamma of 2.4x10;{-7} at the 90% confidence level. Upper limits on the branching ratios in the mass region of X from 194.3 to 219.3 MeV/c;{2} are also presented.

Search for the Decay K L0-->pi0nu nu[over].

We performed a search for the K L0-->pi0nu nu[over] decay at the KEK 12-GeV proton synchrotron. No candidate events were observed. An upper limit on the branching ratio for the decay was set to be 6.7 x 10(-8) at the 90% confidence level.

Simple fluctuation of Ca2+ elicits the complex circadian dynamics of cyclic AMP and cyclic GMP in Paramecium.

The circadian dynamics of cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) were simulated in Paramecium multimicronucleatum. The mathematical functions determined closely mimic the Ca2+ dependence of adenylate cyclase (AC) and guanylate cyclase (GC) activities as documented in P. tetraurelia. Patterns of cAMP concentration ([cAMP]), cGMP concentration ([cGMP ]), and the ratio [cGMP]/[cAMP] were calculated with respect to Ca2+ concentrations ([Ca2+]) fluctuating sinusoidally with a period of 24 hours at three different levels: low, medium, and high. The functions displayed varying patterns of [cAMP] characteristic for [Ca2+] fluctuating at each level, while patterns of [cGMP] and [cGMP]/[cAMP] almost paralleled [Ca2+] fluctuations. Similar patterns were observed for actual [cAMP] and [cGMP] measured during the light/dark cycle in P. multimicronucleatum, grown in axenic media additionally containing [Ca2+] at 25 (low), 100 (medium), or 400 (high) microM, respectively. The coincidence between simulated and measured fluctuations of [cAMP] and [cGMP] suggests that the circadian fluctuations of intracellular [Ca2+] primarily stimulate activities of AC and GC via their different degrees of Ca2+ dependence, which are ultimately responsible for the circadian spatiotemporal organization of various physiological functions in Paramecium.

Neuronal activity in monkey visual areas V1, V2, V4 and TEO during fixation task.

We analyzed 577 neurons recorded from visual areas V1, V2, V4, and the inferotemporal area (TEO) of macaque monkeys, which performed a visual fixation task and a spot-off-on (blink) test during the fixation period. Among these neurons, 35% were defined as task-related cells, because they gave responses at the task-start, fixation, or task-end periods but were unresponsive to the spot blink, which was physically identical to these stimuli. Blink-responsive cells accounted for 29% and task-unresponsive cells for 30% of the neurons. The task-related response was large and frequent in V4 (34%) and TEO (41%), but small and less frequent in V1 (31%) and V2 (27%). Other observations further demonstrated nonsensory activities in these areas: In some cells, response to the fixation spot was inhibitory, whereas light stimulation on the fovea was excitatory; some V1 and V2 cells had color-irrelevant responses, and some cells responded to the spot-off only when the monkey regarded it as a task-end cue.

[In vitro study on the effect of sex steroid and growth factor on growth and laminin, collagen IV, and tissue plasminogen activator production of normal endometrial cells and endometrial cancer cells in culture].

The mechanism of the invasion and proliferation of endometrial cancer is closely related to interactions between the endometrial glands and stroma. In this study, we examined the biological role of sex steroids (estradiol; E2, progesterone; P) and growth factors (epidermal growth factor; EGF, transforming growth factor-beta; TGF-beta) on cell growth and laminin, collagen IV and tissue plasminogen activator (t-PA) production of normal endometrial cells and endometrial cancer cells in culture. Normal endometrial gland cells and stromal cells, and endometrial cancer cell lines (Ishikawa, OMC-2) were used. E2, P, EGF and TGF-beta were added to the culture in physiological concentrations. The growth of normal endometrial gland cells was promoted by E2 and EGF, whereas that of Ishikawa cells and OMC-2 cells was promoted by EGF. E2 enhanced the effects of EGF in normal endometrial gland cells. The growth of normal endometrial stromal cells was not affected by them. OMC-2 was inhibited by anti-EGF receptor antibody. On the other hand, the production of laminin and collagen IV of these cultured cells was inhibited by EGF and promoted by TGF-beta, whereas that of t-PA was promoted by EGF and inhibited by TGF-beta. These results suggest that the growth of normal endometrial gland cells with estrogen receptor (ER) is controlled by both E2 and EGF, whereas that of endometrial cancer cells is affected only by EGF, and those cells without ER depend particularly on the autocrine growth mechanism of EGF.(ABSTRACT TRUNCATED AT 250 WORDS)

[Study on the management of dysplasia of the uterine cervix].

In this study, we investigated problems on the management of dysplasia on the basis of our clinical data obtained in the past ten years. In addition, we also examined the biological significance of protooncogene expression and human papilloma virus (HPV) infection in the initiation and promotion of dysplasia. Among 540 cases of dysplasia we have managed, 48.8% of the cases of mild, moderate and severe dysplasia which we followed up for more than 6 months regressed, and 24.1% of the cases progressed. The cure rate for laser therapy based on the follow up for 6 to 96 months was significantly high (97.9%) in 342 cases treated by the cone method, and low (89.5%) in 38 cases treated by the vaporization method. Preoperative histological findings confirmed 60.5% of postoperative findings, and several early cervical carcinomas were found in preoperative cases of dysplasia by laser conization. Among 28 cases (8.2%) of incomplete excision, 24 cases (85.7%) regressed spontaneously. On the other hand, the positive rate of immunostaining of epidermal growth factor receptor (EGF-R) and c-myc oncogene product (c-myc protein) increased from mild or moderate to severe dysplasia, and the positive rate for EGF-R was significantly high (80.0%) in the progressive group. The positive rate for HPV genome was quite low (16.0%) in dysplasia. Among them, EGF-R was most associated with the prognosis of dysplasia. These results suggest that laser conization should be performed for many cases of dysplasia because of the preoperative possibility of the existence of early cancer, and EGF-R is also useful in determining the necessity for therapy for dysplasia.

[In vitro studies on the expression of c-myc oncogene product in gynecological cultured cancer cells].

In this study, immunocytochemical and biochemical detection of c-myc protein in gynecological cultured cancer cells were performed together with gene expression of the cells. OMC-1 (cervical squamous carcinoma cell line), OMC-2 (endometrial adenocarcinoma cell line), OMC-3 (ovarian mucinous adenocarcinoma cell line) and OMC-4 (cervical adenocarcinoma cell line) were used. Immunocytochemically, c-myc protein was detected in both nuclei and cytoplasms of cultured cells when they were fixed in 95% ethanol, 10% formalin and 4% paraformaldehyde (PFA) including 10mM NaCl. However, it was detected in the nuclei of almost all of the cells in nuclei of the cells when they were fixed in 4% PFA including 1,000mM NaCl. Western blotting against a nuclear fraction of the cells demonstrated 66Kd protein in OMC-1 and 62Kd protein in OMC-2,3,4, respectively. They were completely absorbed by c-myc synthetic peptide. However, there was no reaction against the cytoplasmic fraction of the cells. Slot blot hybridization against the DNA of the cells demonstrated 15 times and 5 times c-myc gene amplification in OMC-2 and OMC-4, respectively. These results suggest that OMC-1,2,3,4 can be used as positive controls for the immunocyto- and histochemical detection of c-myc protein in clinical materials. However, it must be noted that the redistribution of c-myc nuclear protein into the cytoplasm may occur in the fixation process.

Neuronal activity in visual, auditory and polysensory areas in the monkey temporal cortex during visual fixation task.

The activity of 252 neurons in the inferotemporal visual area TEO, the superior temporal auditory area (AA), and the superior temporal polysensory area (STP) during the performance of a visual spot-fixation task and two variations, blink and tone tests, was examined in two behaving monkeys. A considerable number of not only TEO cells (45%) but also AA (29%) and STP (34%) cells were activated during the spot-fixation task, but unresponsive to the blanking of the spot during the fixation stage in the blink test. In addition, it was found that the activity of a third of the TEO, AA and STP cells which fired during the task-start stage in the spot-fixation task was modulated by cross-interaction between spot and tone simultaneously presented in the tone test: among these, the spot-induced activity of all TEO cells was enhanced by the tone, whereas the spot-induced activity of all AA and STP cells was suppressed by the tone. These findings are discussed in relation to the process of attending selectively to a fixation-spot.

Two-stage model of visual pattern discrimination learning in macaque monkeys (Macaca mulatta and Macaca fuscata).

To investigate the nature underlying the process of pattern discrimination learning, a series of seven experiments on seven working assumptions were undertaken. The main findings are as follows. The pattern discrimination learning consists of two time-dependent stages: The initial or first learning stage is the period of performance at chance, and the succeeding or second stage is the period of performance from just above the chance to a criterion level. The duration of the first stage is dependent on the degrees of cue-response separations, whereas that of the second stage is independent of. During the first stage, monkeys do not attend to the discriminative cue even at small cue-response separations, whereas during the second stage, they achieve pattern discrimination, or pattern perception and cognition, regardless of cue-response separations. After having learned the first pattern task with a cue-response separation, they learned new pattern tasks by means of the second stage, showing marked saving of the duration of the first stage. The findings in the present studies indicate that the first stage of learning is predominantly involved in the process of attending to the discriminative cues remote from the response site (a selective attention to the cue), whereas the second stage is concerned with the process of perception and cognition of the discriminative cue.

A role of amygdala in visual perception and cognition in macaque monkeys (Macaca fuscata and Macaca mulatta).

To elucidate the role of the amygdala in visual perception and cognition, the effects of ablations of the amygdala and inferotemporal cortex on several visual tasks were compared with each other, and also the distribution patterns of the projections between them were investigated. The findings indicate that the inferotemporal cortex plays a critical role in visual perception, cognition and memory, whereas the amygdala is involved fundamentally in controlling emotional and motivational behavior. However, the amygdala is concerned with vision in the following ways: It receives neutral visual information highly processed in the visual cortex, invests the information with emotional and motivational significance through interactions with the cortical and subcortical systems of emotion and motivation, and then it returns the information coded to the visual areas to be re-processed; to be consciously perceived in area TEO, and to be meaningfully cognized, recognized and memorized in areas TE and TEG. Therefore, two channel model regarding the mechanism of visual information processing in the inferotemporal cortex is proposed: A first channel is concerned with processing neutral information, while the second one, with processing meaning information coded emotionally and motivationally in the amygdala. In addition, the present studies demonstrate that area TEG, which is cytoarchitecturally a transitional area between areas TE and TG and whose functional significance has remained unclear, is involved significantly in visual cognition rather than visual perception.

[Bone marrow suppression in gynecological patients with malignant tumor treated with combination chemotherapy cyclophosphamide, pirarubicin and cisplatin].

We treated 14 patients with cyclophosphamide, adriamycin and cisplatin (CAP), and 16 patients with cyclophosphamide, Pirarubicin and cisplatin (CTP). Hematological changes in the peripheral blood were compared in the two groups to determine whether there was any difference in bone marrow suppression. 1) The lowest leukocyte counts were similar in the two groups. The leukocyte count reached its nadir at 11.6 +/- 2.1 days in the CTP group and at 15.1 +/- 2.8 days in the CAP group, a significant difference (p less than 0.01). 2) The leukocyte count recovered rapidly in the CTP group and was significantly higher (p less than 0.01) at 3 to 4 weeks than in the CAP group, and it returned to the pretreatment level in the CTP group in the fourth week. 3) The platelet count reached its lowest level in the second week in both groups. In the CTP group, it was significantly higher (p less than 0.01) than in the CAP group. 4) Reticulocyte count reached its lowest level in the first week in both groups, and then started increasing. 5) In the CTP group, a course of treatment was 28.0 +/- 2.3 days and it was 29.5 +/- 2.3 days in the CAP group. In 28% of the CPA group, it took 30 days or more for the leukocyte count to return to normal after one course, while none of the CTP group did the leukocyte count remain low for 30 days. These results show that CTP causes more rapid bone marrow suppression (particularly leukocytopenia) than CAP, does but that a recovery is more rapid with CTP. These CTP may be a better form of treatment than CAP.

[A study of the expression of class II antigen on uterine cervical cancer cells and cell lines].

An immunohistochemical method with monoclonal antibody to DR antigen was used to study class II antigens and HLA-DR antigen in 20 patients with uterine cervical cancer. Eight patients had various amounts of DR antigen. Regional infiltrating lymphocytes were also examined with anti-Leu 1, Leu 2a, Leu 3a, and Leu 10. Among the many infiltrating T cells, Leu 3a-positive cells were relatively predominant surrounding the cancer nests which contained DR antigen. Cervical cancer cell lines OMC-1 and OMC-4 both demonstrated DR antigen. Interferon (IFN)-gamma treatment enhanced the expression of DR antigen in OMC-1 and OMC-4. The DR antigen in OMC-1 and OMC-4 were capable of stimulating allogenic lymphocytes in mixed lymphocyte reaction (MLR), and their stimulatory activity was significantly enhanced by IFN-gamma treatment. These results demonstrated the expression of class II antigen, especially DR, on some cervical cancer cells and cell lines and showed that the DR antigen in uterine cancer cell lines can stimulate MLR.

[EGF receptor and effects of EGF on growth and tumor marker secretion in uterine cervical cancer cells].

Effects of EGF on proliferation and tumor marker secretion of cervical cancer cells are reported together with the characteristics of EGF receptors on the cells. TA-4 producing cell line (OMC-1) originating from cervical squamous cell carcinoma and CA-125 producing cell line (OMC-4) originating from cervical adenocarcinoma, were used. Scatchard plot of EGF binding to OMC-1 indicated a single class of binding sites with a dissociation constant (Kd) of 360pM, whereas that of OMC-4 was curvilinear suggesting two classes of binding sites with a Kd of 170pM and 510pM. The theoretical maximum number of binding sites of OMC-1 and OMC-4 was 2.4 X 10(4) and 1.6 X 10(5), respectively. Effects of EGF on growth were studied by monitoring cell number and the incorporation of 3H-thymidine into the DNA of the cells. OMC-1 was stimulated by EGF at low concentrations (0.01-0.1nM) and inhibited at higher concentrations. OMC-4 was not stimulated by EGF. The TA-4 secretion of OMC-1 was slightly stimulated by EGF at low concentrations (0.01-1nM) and significantly stimulated at high concentration (10nM). The CA-125 secretion of OMC-4 was not stimulated by EGF. These results suggest that there are some differences between cervical squamous cell carcinoma and adenocarcinoma in the mechanisms of regulation of proliferation and tumor marker secretion by EGF.

Polysensory properties of neurons in the anterior bank of the caudal superior temporal sulcus of the macaque monkey.

1. We examined the sensory properties of cells in the anterior bank of the caudal part of the superior temporal sulcus (caudal STS) in anesthetized, paralyzed monkeys to visual, auditory, and somesthetic stimuli. 2. In the anterior bank of the caudal STS, there were three regions distinguishable from each other and also from the middle temporal area (MT) in the floor of the STS and area Tpt in the superior temporal gyrus. The three regions were located approximately in the respective inner, middle, and outer thirds of the anterior bank of the caudal STS. These three regions are referred to, from the inner to the outer, as the medial superior temporal region (MST), the mostly unresponsive region, and the caudal STS polysensory region (cSTP), respectively. 3. The extent of MST and its response properties agreed with previous studies. Cells in MST responded exclusively to visual stimuli, had large visual receptive fields (RFs), and nearly all (91%) showed directional selectivity. 4. In the mostly unresponsive region, three quarters of cells were unresponsive to any stimulus used in this study. A quarter of the cells responded to only visual stimuli and most did not show directional selectivity for moving stimuli. Several directionally selective cells responded to movements of three-dimensional objects, but not of projected stimuli. 5. The response properties of cells in the superficial cortex of the caudal superior temporal gyrus, a part of area Tpt, external to cSTP were different from those of cells in the three regions in the anterior bank of the STS. Cells in Tpt were exclusively auditory, and had much larger auditory RFs (mean = 271 degrees) than those of acoustically-driven cSTP cells (mean = 138 degrees). 6. The cSTP contained unimodal visual, auditory, and somesthetic cells as well as multimodal cells of two or all three modalities. The sensory properties of cSTP cells were as follows. 1) Out of 200 cells recorded, 102 (51%) cells were unimodal (59 visual, 33 auditory, and 10 somesthetic), 36 (18%) cells were bimodal (21 visual+auditory, 7 visual+somesthetic, and 8 auditory+somesthetic), and four (2%) cells were trimodal. Visual and auditory responses were more frequent than somesthetic responses: the ratio of the population of cells driven by visual: auditory: somesthetic stimuli was 3:2:1. 2) Visual RFs were large (mean diameter, 59 degrees), but two-thirds were limited to the contralateral visual hemifield. About half the cells showed directional selectivity for moving visual stimuli. None showed selectivity for particular visual shapes.(ABSTRACT TRUNCATED AT 400 WORDS)

[Immunohistochemical studies on epidermal growth factor receptor in experimental squamous cell carcinoma of the uterine cervix of mice].

The tissue localization of epidermal growth factor receptor (EGF-R) in experimental squamous cell carcinoma of the mouse uterine cervix was examined immunohistochemically. Carcinoma was induced by the insertion of a 20-methylcholanthrene (MC)-impregnated thread into the cervical canal of the mouse. Tissue sections (of normal columnar epithelium, proliferation, atypical proliferation, early invasive carcinoma, invasive carcinoma and metastatic carcinoma) were stained by the avidin/biotin immunoperoxidase technique using anti-EGF-R monoclonal antibody. Normal columnar epithelium was negative for EGF-R, whereas proliferation was partly positive. The lesions of atypical proliferation and early invasive carcinoma had a positive staining for EGF-R. The staining for EGF-R declined in the lesion of invasive carcinoma. Metastatic carcinoma was not stained for EGF-R. These results suggest that EGF-R may play an important role in the early stage of carcinogenesis of the mouse uterine cervix induced by 20-MC.

Direct projections from the ventral TE area of the inferotemporal cortex to hippocampal field CA1 in the monkey.

Anterogradely labeled terminals were found densely in field CA1, but not in any other field, of the hippocampal formation following injections of horseradish peroxidase into the ventral TE area of the inferotemporal cortex, whereas no label was seen in any field of the hippocampal formation following injections into the dorsal TE area. The labeled terminals were distributed mainly in a medial part of the stratum moleculare of field CA1 throughout its rostrocaudal extent. The present finding provides the first demonstration of direct projections from the inferotemporal cortex to the hippocampal formation.