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Biomedical subjects

T Tsujimoto

Publications and source records attributed to T Tsujimoto.

At least 55 records · Page 3Linked to original sources
PubMed1996

Plasma cells induce apoptosis of pre-B cells by interacting with bone marrow stromal cells.

By using two-color phenotypic analysis with fluorescein isothiocyanate-anti-CD38 and phycoerythrin-anti-CD19 antibodies, we found that pre-B cells (CD38+CD19+) signifcantly decreased depending on the number of plasma cells (CD38++CD19+) in the bone marrow (BM) in the cases with BM plasmacytosis, such as myelomas and even polyclonal gammopathy. To clarify how plasma cells suppress survival of pre-B cells, we examined the effect of plasma cells on the survival of pre-B cells with or without BM-derived stromal cells in vitro. Pre-B cells alone rapidly entered apoptosis, but interleukin-7 (IL-7), a BM stromal cell line (KM-102), or culture supernatants of KM-102 cells could support pre-B cell survival. On the other hand, inhibitory factors such as transforming growth factor-beta1 (TGF-beta1) and macrophage inflammatory protein-1beta (MIP-1beta) could suppress survival of pre-B cells even in the presence of IL-7. Plasma cells alone could not suppress survival of pre-B cells in the presence of IL-7, but coculture of plasma cells with KM-102 cells or primary BM stromal cells induced apoptosis of pre-B cells. Supernatants of coculture with KM-102 and myeloma cell lines (KMS-5) also could suppress survival of pre-B cells. Furthermore, we examined the expression of IL-7, TGF-beta1, and MIP-1beta mRNA in KM-102 cells and primary stromal cells cocultured with myeloma cell lines (KMS-5). In these cells, IL-7 mRNA was downregulated, but the expression of TGF-beta1 and MIP-1beta mRNA was augmented. Therefore, these results suggest that BM-derived stromal cells attached to plasma (myeloma) cells were modulated to secrete lesser levels of supporting factor (IL-7) and higher levels of inhibitory factors (TGF-beta1 and MIP-1beta) for pre-B cell survival, which could explain why the increased number of plasma (myeloma) cells induced suppression of pre-B cells in the BM. This phenomenon may represent a feedback loop between pre-B cells and plasma cells via BM stromal cells in the BM.

ADP-ribosyl Cyclase↗
PubMed1996

Frontal mental theta wave recorded simultaneously with magnetoencephalography and electroencephalography.

Frontal mental theta waves were recorded simultaneously with magnetoencephalography (MEG) and electroencephalography (EEG) in normal subjects. MEG analyses demonstrated that theta burst activities distribute widely in the frontal cortices of both the cerebral hemispheres during concentration on mental calculation. On the other hand, EEG showed the theta activities seemed maximal on the frontal midline part (Fz), as if they might have been generated mainly in the frontal midline cortical area.

Adult↗
PubMed1996

Changes in the distribution of cells expressing tumour-associated antigen in lymph nodes during the progression of enzootic bovine leukosis.

A monoclonal antibody (MAb), c143, that recognizes a tumour-associated antigen that is "upregulated" on neoplastic B cells in cattle with enzootic bovine leukosis (EBL), was used as a marker to study disease progression. An immunohistochemical examination of neoplastic tissue and superficial cervical lymph nodes from 14 animals with EBL revealed three morphologically definable stages of change in the structure of lymph nodes, associated with the distribution of c143-positive cells: (1) the presence of c143-positive cells at the marginal sinus with no apparent changes in lymph node structure; (2) the presence of positive cells extending into and distorting the architecture of the lymph node, with clear evidence of proliferation before overt changes (enlargement of lymph nodes) were evident; and (3) the presence of positive cells throughout the lymph node with total disruption of lymph node structure when clinical signs of lymph node enlargement were evident. The results indicated that the bovine leukaemia virus-transformed lymphocytes or neoplastic cells in peripheral blood accumulate in the marginal sinus area at the earliest stages, and subsequently proliferate and infiltrate into follicles, leading to the development of clinical signs of lymphosarcoma.

Animals↗
PubMed1996

Studies on integrative functions of the human frontal association cortex with MEG.

Our MEG studies on the human frontal association cortex are briefly reviewed. (1) The no-go potential was first found at go/no-go reaction-time hand movement task with discrimination between different colour light stimuli in the prefrontal cortex of monkeys. The potential was recorded in human subjects with EEG over the scalp, but its current dipoles could be localized only by use of MEG, in the dorsolateral part of the frontal association cortex in both cerebral hemispheres. The function for no-go decision and subsequent suppressor action was thus substantiated in the human frontal cortex. (2) Utterance of a short noun in Japanese was found to be initially preceded by an activity in the lower lateral part of the frontal lobe and then by that around the central sulcus. The area of the former, often in both hemispheres, appears to correspond to Broca's motor speech centre and that of the latter, always in both hemispheres, to correspond to the motor-somatosensory cortices. (3) Intensive and continuous concentration on mental calculation and some 'abstract' thinking for a few minutes were often associated with magnetic theta (5-7 Hz) wave bursts in the frontal part of the scalp. Dipole fitting suggested that the electrical current dipoles occur successively and scattered in wide areas of the frontal lobe on both sides. They are to be called "frontal mental theta wave", revealing dynamic and active participation of the frontal lobe in mental functions.

Adult↗
PubMed1996

Identification of early plasma cells in peripheral blood and their clinical significance.

In the peripheral blood (PB) we detected so-called early plasma cells that might already be committed to entering the bone marrow (BM). By two-colour staining with FITC-anti-CD38 antibody, their intensity (CD38++) of expression of CD38 antigen was between that of germinal centre (GC) B cells (low expression (CD38+)) and that of BM plasma cells (high expression (CD38++)), and their phenotype was CD38++ CD19+ CD10- CD20- CD21+ CD24- CD39+ CD5- VLA-4+ VLA-5- MPC-1- without expression of surface membrane IgM (SmIgM). Morphological and immunological examination of the sorted cells confirmed that they were plasmacytoid cells with expression of cytoplasmic IgG (cIgG). Variations of these early plasma cells were examined in various diseases. In active systemic lupus erythematosus, bacterial septicaemia and liver cirrhosis, early plasma cell levels were significantly increased in PB, and after subsidence of such inflammation (inactive states) these cells returned to normal levels. In contrast, normal early plasma cells were significantly suppressed in myelomas, whilst normal or slightly increased numbers of early plasma cells was found in benign monoclonal gammopathy (BMG). In addition, the number of normal early plasma cells returned to a normal level in myeloma cases with complete responses. Therefore, early plasma cells were identified phenotypically, and an increase and decrease in these cells in PB may reflect mobilization and suppression, respectively, of activated B cells into BM plasma cells.

ADP-ribosyl Cyclase↗
PubMed1995

Clinical and chronobiological effects of light therapy on nonseasonal affective disorders.

Light therapy (bright or dim light) was given at different times (morning or evening) to 27 unmedicated patients with nonseasonal depression (according to DSM-III-R criteria) and 16 normal volunteers. Circadian rhythms in body temperature were measured before and after light therapy. Bright light significantly improved clinical symptoms of depression, as measured by the Hamilton Rating Scale for Depression (HRSD), independent of the time of phototherapy. Dim light therapy had no effect on HRSD scores. Circadian rhythms of body temperatures in patients with affective disorder were more sensitive to the entraining effects of bright light than those of normal subjects, but these effects were not related to clinical improvement. Bright light exposure has an antidepressant effect on patients with nonseasonal depression, but the effect is unlikely to be mediated via the same circadian system that regulates body temperature.

Body Temperature↗
PubMed1995

Expression of CD21 antigen on myeloma cells and its involvement in their adhesion to bone marrow stromal cells.

The mature myeloma cells express very late antigen 5 (VLA-5) and MPC-1 antigens on their surface and adhere to bone marrow (BM) stromal cells more tightly than the VLA-5-MPC-1- immature myeloma cells in vitro. The VLA-5 and MPC-1 antigens possibly function as two of the molecules responsible for interaction of mature myeloma cells with BM stromal cells. However, the immature myeloma cells do interact with BM stromal cells, and it is unclear which adhesion molecules mediate their interaction. In this study, we found that both immature and mature myeloma cells expressed CD21, an adhesion molecule known to bind to CD23. CD21 was also detected on normal plasma cells. To evaluate the role of CD21 expression on myeloma cells, two myeloma cell lines, NOP-2 (VLA-5-MPC-1-) and KMS-5 (VLA-5+MPC-1+), were used as representatives of immature and mature myeloma cell types, respectively, and an adhesion assay was performed between the myeloma cell lines and BM stromal cells. Antibody-blocking results showed that adhesion of the mature type KMS-5 to KM102, a human BM-derived stromal cell line, or to short-term cultured BM primary stromal cells was inhibited by monoclonal antibodies (MoAbs) against CD21, VLA-5, and MPC-1, and inhibition of adhesion of the immature type NOP-2 to KM102 by the anti-CD21 MoAb was observed as well. Furthermore, CD23 was detected on KM102. Treatment of KM102 with an anti-CD23 MoAb also inhibited adhesion of either KMS-5 or NOP-2 to KM102. Therefore, we propose that CD21 expressed on myeloma cells likely functions as a molecule responsible for the interaction of immature myeloma cells as well as mature myeloma cells with BM stromal cells, and CD23 may be the ligand on the stromal cells for the CD21-mediated adhesion.

Base Sequence↗
PubMed1995

Estimates for the pool size of releasable quanta at a single central synapse and for the time required to refill the pool.

Local superfusion of limited dendritic areas with hypertonic or hyperkalemic solutions stimulates the release of quanta from a small population of synapses made on rodent hippocampal neurons maintained in primary culture, and each quantal event can be detected in the postsynaptic neuron. With maintained stimulation, the initial release rate is about 20 quanta per sec per synapse, and this rate declines exponentially to a final low level. These observations can be interpreted as depletion of available quanta and, with this interpretation, a bouton would contain one to two dozen quanta in its readily releasable pool. Tests with a second application of the solution that produces release reveal that the pool of readily releasable quanta is replenished with a time constant of about 10 sec (36 degrees C). The pool of quanta defined in this way may correspond to the population of vesicles docked at the bouton's active zone.

Animals↗
PubMed1995

Differentiation of early plasma cells on bone marrow stromal cells requires interleukin-6 for escaping from apoptosis.

The bone marrow (BM) is well known to be the major site of Ig production in secondary immune responses; thus, the microenvironment of BM is considered to be essential for final differentiation of plasma cells. We identified in the peripheral blood (PB) early plasma cells (CD38++CD19+VLA-5-) committed to entering the BM. The sorted early plasma cells rapidly entered apoptosis in vitro, but these cells could survive and further differentiate into mature plasma cells (CD38 CD19+) just as BM plasma cells in the presence of a BM-derived stromal cell line (KM-102). Culture supernatants of KM-102 cell lines could also support survival of these cells, and antibody to interleukin-6 (IL-6) completely blocked the effect of these supernatants. Furthermore, recombinant IL-6, but not IL-1 or IL-3, could support their survival and their differentiation into mature plasma cells (CD38 CD19+VLA-5+) with expression of VLA-5 mRNA. Therefore, here is direct evidence that early plasma cells found in the PB differentiated into mature plasma cells with stromal cell-derived IL-6 in vitro; thus, BM stromal cells control the final checkpoint of plasma cell differentiation with secretion of IL-6 in the BM.

ADP-ribosyl Cyclase↗
PubMed1995

Motor speech centres in the frontal cortex.

Activities of the frontal cortices in both cerebral hemispheres preceding utterance of a short word were recorded and analyzed with multichannel SQUID gradiometers. Light stimuli of two different colours of 500 ms duration were delivered in front of a subject at random time intervals and in irregular order of the different colours. The subject should respond to either of the stimuli by uttering a short word, e.g., 'en' [en] ('round' in Japanese) or another by a short simple voice without meaning as a word, e.g., 'e' [e]. The initial sounds of both voices are to be the same, i.e., 'e' [e] in these examples. The 37 gradiometers covering either the left or the right frontal-parietal part of the hemisphere recorded different magnetic fields between the word and the simple voice. Magnetic fields averaged 100 times at the onset of the stimuli revealed that the utterance of a word is preceded by significant magnetic field changes at a peak latency of 120-165 ms from the onset of light stimuli, whereas the utterance of a simple voice is not preceded by such changes. At a peak latency of 160-190 ms, about 20-40 ms before the start of perioral EMGs, both the utterances are commonly preceded by magnetic field changes. Dipole fittings based on these magnetic fields suggest that the earlier magnetic fields reflect electrical activities in the ventral lateral part of the frontal association area, usually in both left and right hemispheres, and that the later fields represent those in the sensorimotor area in both the hemispheres. That part of the frontal association area appears to be the centre for organizing words to speak and to correspond possibly to the Broca's speech area.

Adult↗
PubMed1995

A new phenotypic classification of bone marrow plasmacytosis.

Here, we propose a new phenotypic classification of bone marrow plasmacytosis. By 2-color phenotypic analysis with FITC anti-CD38 and PE anti-CD19, -CD56, -VLA-5 or MPC-1 antibody, plasma cells are easily identified on the histogram, even though no more than 1% of plasma cells are found in the bone marrow. Hence, plasma cells are phenotypically classified into polyclonal (reactive) (CD19+CD56-) or monoclonal (neoplastic) plasma cells (mostly CD19-CD56+), and furthermore immature (VLA-5-MPC-1-), intermediate (VLA-5-MPC-1+) and mature plasma cells (VLA-5+MPC-1+). According to these findings, plasmacytosis in the bone marrow can be classified into polyclonal marrow plasmacytosis (POMP) and monoclonal marrow plasmacytosis (MOMP) states. The MOMP state is further subclassified into MOMP-1 and MOMP-2, MOMP-3 and MOMP-4; MOMP-1 is defined by co-existence of monoclonal plasma cells and polyclonal plasma cells, and MOMP-2 to MOMP-4 are dependent on increased proportions of VLA-5-MPC-1- immature myeloma (plasma) cells. We found that the cases of benign monoclonal gammopathy (BMG) according to the conventional classification were in the MOMP-1 state, and myelomas could be classified into the MOMP-2 to MOMP-4 state. Subclassification of the MOMP state may be useful in determining the prognosis of myelomas, where an increase in immature myeloma cells is reported to correlate well with their aggravation during the clinical courses. Therefore, this new phenotypic classification of bone marrow plasmacytosis (POMP and MOMP-1 to MOMP-4) will contribute to differential diagnosis and understanding of therapeutic responses and prognosis in myelomas.

Antigens, CD19↗
PubMed1995

Safety and pharmacokinetics of iotrolan in hysterosalpingography. Retention and irritability compared with Lipiodol.

RATIONALE AND OBJECTIVES: The authors compared the safety and pharmacokinetics of Iotrolan (water-soluble) in hysterosalpingography (HSG) with those of Lipiodol (oil-soluble). METHODS: Iotrolan and Lipiodol were administered intraperitoneally at doses of 100 mg iodine/kg to female rabbits. Retention in the body was investigated by x-ray imaging, plasma kinetics, and urinary and fecal excretion. Irritability in the abdomen was investigated by histologic examination. RESULTS: Iotrolan was entirely excreted into the urine within 2 days after administration. Conversely, Lipiodol was excreted into the urine, had a half-life of 50 days, and was retained for more than 21 days in the abdomen. Iotrolan induced no inflammatory reaction in the abdomen, whereas Lipiodol induced a marked abdominal inflammatory reaction, including granuloma formation. Iotrolan had no effect on iodine concentration in the thyroid; Lipiodol increased iodine concentration significantly. CONCLUSIONS: Iotrolan, which is a water-soluble and nonionic dimeric contrast medium, has potential greater safety for use in HSG than Lipiodol.

Abdomen↗
PubMed1995

High proportions of VLA-5- immature myeloma cells correlated well with poor response to treatment in multiple myeloma.

Using two-colour phenotypic analysis with anti-CD38 antibody, human myeloma cells can be classified into VLA-5- immature and VLA-5+ mature cells. We examined the relationship between variations of these subpopulations and clinical responses during treatment in multiple myeloma (MM). 39 patients with MM were treated with combined chemotherapy. First estimation of clinical responses after induction therapy showed that early clinical responses were correlated with the percentage of immature myeloma cells present after induction therapy (P < 0.01), not at diagnosis. After three courses of cyclic maintenance therapy, immature myeloma cells significantly decreased in proportion along with a decrease in total myeloma cells in maintained or more responsive cases (P < 0.01). On the other hand, immature myeloma cells were still found in high proportions in nonresponsive cases with no change (NC) or minor response (MR) (P < 0.01). Furthermore, in relapsing cases from partial response (PR) or progressive disease (PD) from nonresponsive cases, immature myeloma cells increased markedly. Therefore these results show that high proportions of VLA-5- immature myeloma cells remaining after induction therapy and during maintenance therapy correlate well with a declining clinical course of MM during maintenance therapy.

ADP-ribosyl Cyclase↗
PubMed1994

Dynamic activities of the frontal association cortex in calculating and thinking.

We found 5-7 Hz magnetic theta waves in the frontal association cortex of adult human subjects during calculation and musical imagination by using 37-channel SQUID gradiometers. Simultaneous recording from the left and right cerebral hemispheres with two sets of 37-channel gradiometers revealed that the theta activity appeared in a waxing and waning manner in the frontal cortices of both hemispheres during the mental exercises. Electrical current dipoles for the theta waves were estimated to occur repeatedly and scatteringly in various parts of the frontal lobes of both hemispheres during continuous and intense mental exercises for 2 min. The results suggest a dynamic mode of activities in the frontal association cortex during mental effort such as calculating and thinking.

Adult↗
PubMed1994

Bullous lymphoma of the skin.

We describe an extremely rare case of cutaneous B-cell lymphoma associated with bulla formation. The term, 'bullous lymphoma' is proposed for this variant of cutaneous lymphoma.

Aged↗
PubMed1993

Effect of cooling the dentate nucleus of the cerebellum on hand movement of the monkey.

The functional role of the cerebellum in voluntary movement was investigated by local cooling of the cerebellar nuclei in three Japanese monkeys which performed hand movement tasks in response to visual stimuli. We implanted electrodes in various areas of the cerebral hemispheres to record field potentials in the cortex, and examined effects of the cooling upon the movement and field potentials. Cooling of the dentate nucleus ipsilateral to the moving hand reversibly increased the reaction time and reduced the size of surface-negative, depth-positive (s-N, d-P) field potential in the motor cortex contralateral to the hand. The potential preceded the movement by an almost constant time of about 100 ms in the normal condition. The cooling remarkably prolonged and deviated the time. By shifting the cooling probe to different distances from the nucleus, we noted various decreases of the cooling effect. We also found a close correlation between the size of the s-N, d-P potential and the reaction time, i.e., when the potential was small, the reaction time was long. These findings support the following ideas; the motor command for this task comes to the motor cortex through the cerebello-thalamo-cortical pathway which includes the dentate nucleus, and produces the s-N, d-P potential as EPSP currents in pyramidal neurons in the motor cortex. We also studied self-paced movement task. In some cases, the cooling reduced the size of readiness potential in the motor cortex.

Animals↗