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Biomedical subjects

T Yamamura

Publications and source records attributed to T Yamamura.

At least 163 records · Page 9Linked to original sources

Suppression of lymphocyte spontaneous proliferative response by proteolipid protein peptide in patients with HAM/TSP.

To understand the immune mechanism suggested in HTLV-I-associated myelopathy (HAM/TSP), we investigated T cell response to proteolipid protein (PLP). Because of high autologous proliferative response (APR) of peripheral blood mononuclear cells (PBMC) in culture, the lymphocyte proliferation assay was not useful in this disease. Unexpectedly, however, APR was profoundly (70-98%) suppressed in 6 of 9 cases when PLP peptide 105-124 was added in the culture. PLP peptide 85-104 or 145-159 also suppressed APR in a few cases. Time course study showed that the peptide-mediated suppression became apparent after day 4 in culture. The results can be interpreted as that suppressor cells recognizing the PLP peptides were present in the PBMC of HAM/TSP patients and suppressed the APR as the consequence of antigen specific response. This may indicate that a T cell response to certain PLP determinants is involved in the pathomechanism of HAM/TSP at least in part. Molecular mimicry between PLP and HTLV-I may account for the T cell sensitization to PLP in HAM/TSP.

Adult↗

Flexor sheath closure during delayed primary tendon repair.

We studied the effect of flexor tendon sheath closure on flexor tendon function after delayed primary flexor tendon suture in white leghorn chickens. The tendon suture was carried out after a tendon laceration. In the left foot the tendon sheath was closed after tendon suture, and in the right the sheath was excised over the tendon suture. Tendon gliding, joint motion, the fate of the closed sheath, peritendinous adhesions, and tendon healing were studied. The sutured sheath disappeared after suturing and was associated with poor tendon healing. Sheath closure did not improve flexor tendon function in a delayed primary repair.

Animals↗

Epstein-Barr virus-associated large granular lymphocyte leukemia with cutaneous infiltration.

A 36-year-old man had a high titer of antibody to Epstein-Barr virus (EBV) and recurrent necrotizing papules and nodules on his face and oral mucosa. The disease was diagnosed as CD3+4- 8+ large granular lymphocyte leukemia of T-cell origin. Southern blot analysis demonstrated that EBV DNA was present in CD8+ lymphocytes; EBV antigens were also observed in these lymphocytes. These findings demonstrated that EBV latently infected the leukemic cells and may have played a role in the pathogenesis of this disease. This is the first report of an association between EBV and large granular lymphocyte leukemia of T-cell origin.

Adult↗

Analysis of T cell antigen receptors of myelin basic protein specific T cells in SJL/J mice demonstrates an alpha chain CDR3 motif associated with encephalitogenic T cells.

Experimental autoimmune encephalomyelitis (EAE) is an animal autoimmune disease mediated by CD4+ T cells. Analysis of TCR expression revealed that limited TCR elements (V beta 8.2, V alpha 2 or 4) were utilized by myelin basic protein (MBP) specific T cells in mice with H-2u haplotype and Lewis rats. The usage of a particular beta chain complementarity determining region 3 (CDR3) motif has also been shown. However, it remains unclear to what extent these observations can be extrapolated. Here we studied the TCR sequences of MBP 89-101/I-A(s) specific T cell clones derived from SJL/J mice, using the polymerase chain reaction on reverse transcribed mRNA. Although the V beta usage was less restricted than in H-2u mice, they predominantly utilized V beta 17a and expressed LGG or related motifs in the V beta-D beta-J beta junctions. Furthermore, a single alpha chain rearrangement between V alpha 1.1 and J alpha BBM142 with no N region diversity was preferentially used. Concordantly, immunization with a peptide corresponding to the alpha chain CDR3 was found to significantly alter the clinical course of EAE. Comparison of the published TCR junctional regions demonstrates that the CDR3 motifs (LGG in beta chain, CA*R*NY motif in alpha chains) are expressed by other encephalitogenic clones. Notably, the CA*R*NY was conserved in PL/J mice clones that recognize a distinct MBP-MHC determinant. It suggests that an antigen-independent mechanism may contribute to conserving the alpha chain motif. The implications of these observations are discussed.

Amino Acid Sequence↗

ETA and ETB receptors on single smooth muscle cells cooperate in mediating guinea pig tracheal contraction.

We investigated the distribution of endothelin A (ETA) and ETB receptors in single smooth muscle cells and their contribution to ET-induced contractions of guinea pig trachea. ETA and ETB receptors were detected in smooth muscle membranes (maximum binding capacities of 810 and 360 fmol/mg protein and dissociation constants of 38 and 5.1 pM for 125I-labeled ET-1 and 125I-ET-3, respectively) and visualized autoradiographically in primary cultured cells. ET-1 and ET-3 evoked concentration-dependent increases in intracellular Ca2+ concentration and smooth muscle tension. The half-maximally effective concentrations of ET-1 and ET-3 at inducing contractions were 1.9 and 2.7 nM, respectively. The Ca2+ responses showed tachyphylaxis to both ETs after stimulation with ET-1, but only to ET-3 after stimulation with ET-3. Consecutive applications of ET-3 and ET-1 (10 nM each) classified the cells into ETA dominant (approximately 30%) responding to only ET-1, ETB dominant (approximately 20%) responding to only ET-3, and ETA- and ETB-possessing (approximately 50%) cells responding to both. The ETA antagonist, 10 microM BQ-123, attenuated ET-1-induced contractions but did not affect the ET-3-induced contractions. The results indicate that both receptors coexist in a major population of smooth muscle cells and cooperate in mediating ET-1-induced contractions.

Animals↗

The effect of fentanyl and morphine on neurons in the dorsal raphe nucleus in the rat: an in vitro study.

The dorsal raphe (DR) nucleus is a system of nuclei lying in the midline of the lower brainstem constituting the largest collection of serotonin-containing neurons in the brain. The DR nucleus, which is under the influence of various synaptic inputs containing the excitatory amino acids (EAAs), serotonin and noradrenaline (NA), has been reported to be involved in the process of nociception. We studied the effects of fentanyl and morphine on the firing activity of neurons within the DR nucleus in the rat brain slice preparation in vitro using extracellular recording techniques. The decreased activity of DR neurons induced by these opioids was reversed upon application of naloxone. Since almost all neurons were silent, N-methyl-D-aspartate (NMDA) and noradrenaline were used to excite the DR neurons. Serotonin contained in the DR nucleus acts as a neuromodulator to enhance the excitatory effects of NMDA. All DR neurons were excited by NMDA, whereas 72% of the neurons were excited by NA. NA has a long-lasting effect on the firing activity of the neurons, although the firing pattern was less regular than that induced by NMDA. Of the total number of the DR neurons excited by NMDA and/or NA, 71% were inhibited by fentanyl and 73% by morphine. The results support our hypothesis that these opioids inhibit the firing activity of DR neurons and, in turn, might alter nociception directly and/or indirectly by modifying the central serotonergic system.

Animals↗

[Home therapy approach in cancer patients-chemotherapy (case 2-2)].

We have performed intra-arterial biochemical modulation chemotherapy of 5-FU with Leucovorin for patients with unresectable liver metastases from colorectal cancer. Three regimens were performed. A; weekly bolus injection of 5-FU and Leucovorin (6 cases), B; 7 days continuous injection of 5-FU after bolus injection of Leucovorin (4 cases), C; 5 days simultaneously continuous injection of 5-FU with Leucovorin (6 cases). The results were; response rate was A:0%, B:25%, C:33% and survival rate for patients of C method was better than that for patients of A and B method. Four patients complained mild nausea of less than Grade 2, but only one patient of C method. These results suggest that simultaneously continuous intra-arterial injection of 5-FU with Leucovorin is an excellent therapy for patients with unresectable liver metastases from colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗