[Longitudinal study on dental health of inhabitants in Western areas of Iriomote Island in Okinawa].
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Biomedical subjects
Publications and source records attributed to K Handa.
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We used purified class I antigen incorporated into liposomes to examine the response of secondary cytolytic T lymphocytes (CTL) to chemically modified self. By generating the secondary response in the presence of T cell helper factor, the level of CTL response was limited by CTL recognition of added antigen rather than by helper cell generation of lymphokines. We found a strong secondary response against chemically modified self when spleen cells from trinitrophenyl (TNP)-primed C3H/HeJ mice were stimulated with a) TNP-modified liposomes containing H-2Kk, b) liposomes containing H-2Kk purified from TNP-modified RDM-4 (H-2k) cells, or c) liposomes containing the limited trypsin proteolysis product of H-2Kk that had been directly modified with TNP. In contrast, we were not able to generate a significant CTL response with unmodified H-2Kk incorporated into vesicles along with TNP-modified membrane components lacking H-2Kk. These results suggest that TNP-modified H-2Kk is a major antigenic site recognized by CTL from C3H/HeJ mice after priming against TNP-modified self.
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A 41-year-old male patient underwent transurethral resection for multiple bladder tumors in January, 1979. The pathological examination of the specimen revealed non-invasive transitional cell carcinoma G 2. Thereafter, transurethral coagulation and vesical instillation of various antitumor agents were carried out several times for tumor recurrence during the following eight months. X-ray examination for evaluation of macrohematuria, 15 months following the above treatment, showed left renal pelvic tumor. Left total nephro-ureterectomy was performed in July, 1981. However, microhematuria and class V in urine cytology were continuously observed postoperatively. Right total nephroureterectomy, followed by surgery of the internal shunt, was performed in January, 1982, after diagnosis of renal pelvic tumor by further investigation. Under maintenance hemodialysis, vagotomy and pylorus plastic operation were performed for gastroduodenal bleeding after the above surgery. Total cystectomy and urethrectomy along with irradiation during and after surgery were performed for tumor recurrence in November, 1982 and July, 1983 respectively. Unfortunately, the patient died of multiple liver metastasis and gastro-intestinal bleeding in September, 1983. All the tumor specimens showed the same histological characteristics, i.e., transitional cell carcinoma G 3. Twenty six Japanese cases of epithelial tumors of the bilateral upper urinary tract are reviewed.
In the accompanying paper, we showed that natural killer (NK) cells were a major population in the naive spleens of normal mice that responded directly to a T cell growth factor, interleukin 2 (IL 2), and clonally replicated without other stimulating agents. The cloned cells growing in IL 2 showed a potent NK activity against several NK targets without addition of an NK-activating agent, interferon (IFN). In the present study, therefore, we examined whether these cloned NK cells on their own produced IFN. It was found that all NK clones growing in IL 2 produced IFN in the culture fluids. The titers of IFN produced in the IL 2-containing media correlated well with the number of growing cells. With the culture in the absence of IL 2, neither cell growth nor IFN production could be detected. Addition of Con A into the culture in the IL 2-free media showed no IFN production. The antiserum neutralizing IFN alpha and IFN beta failed to significantly neutralize IFN produced by NK clones. Treatment with either a pH of 2.0 or antiserum neutralizing mouse IFN gamma resulted in a marked reduction of IL 2-induced NK IFN, indicating that a major part of IFN produced was IFN gamma. These results indicate that IL 2 stimulates NK clones to proliferate, accompanied by IFN gamma production. The results also show that an NK clone, when stimulated with Sendai virus, produced a type 1 IFN (IFN alpha and/or IFN beta), suggesting that murine NK cells can produce both type 1 (alpha and/or beta) and type 2 (gamma) IFN, depending on inducers.
The proliferative response of murine natural killer (NK) cells to a T cell growth factor, interleukin 2 (IL 2) was investigated by using the NK-enriched, low-density fractions (F.1) and NK-depleted, T cell-enriched, and high-density fractions (F.3) of normal spleen cells after Percoll-discontinuous density gradient centrifugation. When F.1 and F.3 cells were cultivated with IL 2-containing medium without addition of any other factors, like lectins, feeder layer, or macrophage products, F.1 but not F.3 cells showed an IL 2-dependent proliferative response. Growing populations showed a potent NK activity and consisted largely of cells with a morphology of large granular lymphocyte (LGL) and a surface marker profile characteristic for murine NK cells. By limiting dilution in the liquid culture and colony formation in the soft agar medium, F.1 but not F.3 cells showed a high frequency of clonal replication in IL 2. Almost all growing colonies in either medium showed a typical morphology of LGL. Further, F.1 cells treated with anti-asialo GM1 antibody and C, from which NK cells and cytolytic activity were almost completely abrogated and for which T cells were enriched, conversely formed a few IL 2-dependent colonies. From the colonies in soft agar, 11 clones, all of which showed a typical morphology (LGL), a typical surface profile with the exception of lacking IgG-Fc receptors for NK cells (Thy-1 +/-, Ly-5+, ASGM1+, Lyt-1-, Lyt-2-, Fc gamma R-), and a cytotoxic activity of activated nature, were established and maintained for a period of longer than 1 yr in the medium containing IL 2 alone. These results indicate that a major population in the naive spleens of normal mice that respond directly to IL 2 and clonally replicate without other stimulating factors may be NK cells.
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Hemodynamic responses to prostacyclin (PGI2) were studied in sheep in the conscious state as well as under pentobarbital-halothane anesthesia. PGI2 in doses of 0.02-1.0 microgram/kg were administered as a bolus into the right or left atrium in the conscious sheep. PGI2 decreased systemic arterial pressure (PSA), systemic (SVR) and pulmonary vascular resistance (PVR) and increased cardiac output (CO) and heart rate (HR) in a dose-dependent manner. The changes of each parameter were almost similar regardless of the sites of administration. Pulmonary arterial pressure (PPA) was increased. There was no change in left (PLA) or right atrial pressure (PRA). A bolus administration of 0.5 microgram/kg of PGI2 in the anesthetized sheep produced a decrease in PSA, SVR and PVR, and increase in CO and HR. PPA remained unchanged when administered into the right atrium and increased slightly when administered into the left atrium. PLA and PRA did not change. Comparing hemodynamic responses to 0.5 microgram/kg of PGI2 of the conscious and anesthetized states, decrease in PSA was smaller and increases in CO and HR were greater in the former. Decreases in SVR and PVR were similar in both states. Increase in PPA was greater in the conscious sheep. This data confirms that PGI2 dilates the systemic as well as the pulmonary circulation of the sheep and an inactivation of this compound in the lungs is minimal. Furthermore, it may be suggested that general anesthesia significantly alters hemodynamic responses to PGI2 in the sheep.
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