Abstract Cytotoxic T lymphocytes (CTLs) play an essential role in immunologic responses for tumor rejection. In the past decade, various melanoma tumor–associated antigens (TAAs) have been ...identified, and several clinical trials of vaccination immunotherapy and adoptive immunotherapy using such antigens with or without adjuvants have had fascinating results. However, this has not been the case with oral squamous cell carcinoma (OSCC) because of the difficulty of establishing oral cancer cell lines and CTLs against autologous oral cancer cells. Therefore, few oral cancer antigens have been identified with such CTLs. We herein present the successful establishment of an oral squamous cell carcinoma cell line, POT-1, and an HLA-A24–restricted CTL line (TcPOT-1) from a patient's autologous peripheral blood lymphocytes. TcPOT-1 recognized autologous POT-1 cells in an HLA-A24–restricted manner, and also allogeneic HLA-A24 (+) OSCC cell lines OSC-70 and HSC-2. We also succeeded in isolating two distinct CTL clones from TcPOT-1, HLA-A24–restricted CTL clone 4F11 and HLA-A33–restricted clone 4A11. Both of these clones recognized autologous POT-1 but not allogeneic OSSC cell lines. These data imply that the TcPOT-1 CTL line may include several CTL subpopulations with distinct antigen specificities, such as an HLA-A24–restricted POT-1–specific clone, HLA-A33–restricted POT-1–specific clone, and HLA-A24–restricted allogeneic OSCC-recognizing clone. Therefore, precise analysis of TcPOT-1–recognizing antigens may provide us with important information on as-yet-unknown tumor rejection antigens in OSCC.
The existence of the J-curve in hypertension treatment remains controversial. The major question is whether the increase in mortality from coronary disease is induced by the lowering of blood ...pressure (BP) or by the severity of underlying coronary artery disease. We recruited patients with a history of hypertension (systolic BP (SBP) >160 mmHg and⁄or diastolic BP (DBP) >90 mmHg) and a diagnosis of angina pectoris with angiographically confirmed coronary artery lesion. The relationship among the treated levels of SBP and DBP, the severity of coronary artery lesion, and the clinical consequences were investigated. Among the 234 enrolled patients, 115 experienced further events, 19 of which were serious. There were no significant differences in the average BP of patients with and those without events, but the coronary severity indices (CSI) were significantly greater in patients with events. As a function of DBP from ≤74 to 105≤mmHg, there was a positive association with the incidence of serious events, and a reversed J-curve in CSI with a nadir at 95-104 mmHg. A similar relationship was observed in SBP, but a potentially unfavorable outcome was suggested in the lowest SBP range of ≤124 mmHg. In conclusion, there was no J-curve for DBP in hypertensive patients with angina pectoris; rather, the lower the DBP, the better was the prognosis. Interestingly, the severity of coronary lesion is in a reversed J-curve relation with DBP, suggesting that high BP plays a critical role in serious events in hypertensive patients with moderate coronary artery lesions. (Hypertens Res 2002; 25: 381-387)
The purpose of this study was to verify whether the accuracy of left ventricular parameters related to left ventricular function from gated-SPECT improved or not, using multivariate analysis.
...Ninety-six patients with cardiovascular diseases were studied. Gated-SPECT with the QGS software and left ventriculography (LVG) were performed to obtain left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV). Then, multivariate analyses were performed to determine empirical formulas for predicting these parameters. The calculated values of left ventricular parameters were compared with those obtained directly from the QGS software and LVG.
Multivariate analyses were able to improve accuracy in estimation of LVEF, EDV and ESV. Statistically significant improvement was seen in LVEF (from r = 0.6965 to r = 0.8093, p < 0.05). Although not statistically significant, improvements in correlation coefficients were seen in EDV (from r = 0.7199 to r = 0.7595, p = 0.2750) and ESV (from r = 0.5694 to r = 0.5871, p = 0.4281).
The empirical equations with multivariate analysis improved the accuracy in estimating LVEF from gated-SPECT with the QGS software.
We report on a 14 7/12-year-old Japanese female patient with CHARGE syndrome and CHD7 mutation who also exhibited Kallmann syndrome (KS) phenotype. She had poor pubertal development and apparently ...impaired sense of smell. A GnRH test showed severely compromised responses of LH (<0.5 → <0.5 IU/L) and ESH (<0.5 → 1.2 IU/L), and magnetic resonance imaging delineated hypoplastic olfactory bulbs. Mutation analysis revealed a heterozygous nonsense mutation at exon 33 of CHD7 (7027C>T, Q2343X). The results provide further support for the notion that KS phenotype can be included in the phenotypic spectrum of CHARGE syndrome, and indicate that CHARGE syndrome with KS phenotype is caused by a CHD7 mutation.
We describe a 66-year-old woman who had an alternating bundle branch block consisting of coexisting occurrence of right bundle branch block (RBBB) and left bundle branch block (LBBB) combined with ...Mobitz type II atrioventricular block (AVB). A prolonged PQ interval was associated with the RBBB pattern whereas it was not apparent in the LBBB pattern. Electrophysiologic study revealed that the LBBB pattern was combined with a double His bundle potential. On the other hand, the RBBB pattern was combined with a markedly prolonged HV interval with a low voltage monophasic His bundle potential, which we speculated was the former part of the split His bundle potential seen during the LBBB pattern. A combination of the longitudinal dissociation in the His bundle and the gap phenomenon at the intra-Hisian block portion may account for this observation.
We established a new cell line, HPC-3P4a, with high peritoneal disseminated potential in nude mice. HPC-3P4a was derived from a human pancreatic carcinoma cell line (HPC-3) that had low capacity for ...peritoneal dissemination. HPC-3P4a developed peritoneal dissemination in 10 of 11 (90.9%) cases, whereas parental HPC-3 developed peritoneal dissemination in one of six (16.7%) cases. The metastatic foci in the peritoneum showed essentially the same histologic appearance of parental involvement. The tumorigenicity, motility, and adhesive activity of HPC-3P4a to the extracellular matrix were stronger than were those of the HPC-3. In FACS analysis, HPC-3P4a significantly increased the expression of alpha6 and alpha(v)beta5 integrins, while it decreased alpha2 integrin, hCD44H, and hCD44v 10, as compared with HPC-3. The VEGF production of HPC-3P4a was significantly lower than that of HPC-3. Analysis of gene macroarrays showed a variety of cytokines, interleukin, and other immunomodulatory, and their receptors were up-regulated and down-regulated on an mRNA level in HPC-3P4a cells, compared with HPC-3 cells. Intrasplenic injection of HPC-3P4a produced no liver metastasis. We named our original highly liver metastatic cell line HPC-3H4 (previously reported). This HPC-3H4 cell was established by repeated intrasplenic injection from parental cell HPC-3; thus, it developed high liver metastasis. Moreover, HPC-3H4 developed peritoneal dissemination by intra-abdominal injection. In contrast, HPC-3P4a did not develop liver metastasis by intrasplenic injection. These findings are very interesting and might suggest that the process of hematogenous metastasis differed from that of peritoneal dissemination. Thus, this cell line may be useful for investigating the mechanism of peritoneal dissemination in human pancreatic cancer.
With the growth of the aged population, untreated elderly patients who have malocclusion with prognathism will increase. When a patient with prognathism becomes edentulous, we often experience, ...during treatment, complete dentures not being stable and the patient is not satisfied with the form of the dentures because the relative position of the maxilla and mandible is skeletal Class III. We report a case of mandibular prognathism with edentulous maxilla by orthognathic treatment. The patient is a 58-year-old woman. Her complaint is that because the full maxillary denture is not stable, she cannot bite right and where the mandibular protrusion is. The diagnosis is a mandibular protrusion with edentulous maxilla and partially edentulous mandible (7-4). We made a full maxillary denture and sagittal split ramus osteotomy (SSRO) was performed. After orthognathic surgery, the position of the maxilla and mandible were improved. Thereafter, we made a definitive prosthesis. As the dentures were stable and the mandibular protrusion had improved, the patient was satisfied.
In normal rat and human, most of the nuclei of hepatic parenchymal cells are centrally located in the cytoplasm. However, it is reported that the nuclei of hepatic parenchymal cells are situated at a ...deviated position on sinusoidal surfaces under pathological situations such as chronic hepatitis, hepatocellular carcinoma, adenomatous hyperplasia, or regeneration. During a study on the mechanism of extreme vitamin A-accumulation in hepatic stellate cells of arctic animals including polar bears, arctic foxes, bearded seals, and glaucous gulls, we noticed that these arctic animals displayed the nuclear deviation in hepatic parenchymal cells on sinusoidal surfaces. In this study, we assessed the frequency of hepatic parenchymal cells showing the nuclear deviation on the sinusoidal surfaces in arctic animals. A significantly higher frequency of the nuclear deviation in hepatic parenchymal cells was seen in polar bears (89.8±3.4%), arctic foxes (68.6±10.5%), bearded seals (63.6±8.4%), and glaucous gulls (24.2±5.8%), as compared to that of control rat liver (9.8±3.5%). However, no pathological abnormality such as fibrosis or necrosis was observed in hepatic parenchymal and nonparenchymal cells of arctic animals, and there were no differences in the intralobular distribution of parenchymal cells displaying the nuclear deviation in the livers from either arctic animals and control rats. The hepatic sinusoidal littoral cells such as stellate cells or extracellular matrix components in the perisinusoidal spaces may influence the nuclear positioning and hence the polarity and intrinsic physiological function of parenchymal cells.
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