Intermittent breath holding during moderate bicycle exercise provokes consistent changes in muscle oxygenation and greater blood lactate response.

AIM: This study examined the effect of intermittent breath holding (IBH) on physiological response, including oxygenation in working muscle, to moderate-intensity exercise. METHODS: Thirteen men performed bicycle exercise for 5 min at 65% of peak oxygen uptake with normal breathing (NB) and with IBH. Muscle oxygenation, concentration changes of oxyhemoglobin (ΔOxy-Hb), deoxyhemoglobin (ΔDeoxy-Hb) and total hemoglobin (ΔTotal-Hb), in the right vastus lateralis were continuously monitored using near-infrared spectroscopy (NIRS). Finger capillary blood samples were taken after exercise for analyzing blood lactate concentration (BLa). RESULTS: NIRS parameters showed acute changes to each BH episode in the IBH condition (Total-Hb and ΔOxy-Hb decreased, ΔDeoxy-Hb increased). Accordingly, in the IBH condition, ΔOxy-Hb was lower (P<0.05) and ΔDeoxy-Hb was higher (P<0.05) compared to that in the NB condition, whereas there was no difference in ΔTotal-Hb in the both conditions. BLa levels were greater (P<0.05) in the IBH condition compare to the NB condition. CONCLUSION: These results suggest that IBH during moderate-intensity exercise provokes consistent changes in muscle oxygenation, leading to lower tissue oxygenation. Our data also indicate that exercise with IBH induces higher BLa.

Identification of parathyroid hormone-related protein-derived peptides immunogenic in human histocompatibility leukocyte antigen-A24+ prostate cancer patients.

Parathyroid hormone-related protein (PTHrP) is a key factor in the development of bone metastases, which are a major barrier in treating prostate cancer patients. In this study, we attempted to identify PTHrP-derived peptides immunogenic in human histocompatibility leukocyte antigen (HLA)-A24(+) prostate cancer patients. Among four different PTHrP peptides carrying the HLA-A24 binding motif, both the PTHrP(36-44) and PTHrP(102-111) peptides efficiently induced peptide-specific cytotoxic T lymphocytes from peripheral blood mononuclear cells (PBMCs) of HLA-A24(+) prostate cancer patients. Peptide-stimulated PBMCs showed cytotoxicity against prostate cancer cells in an HLA-A24-restricted manner. Experiments using antibodies and cold inhibition targets confirmed that their cytotoxicity was dependent on PTHrP peptide-specific and CD8(+) T cells. Immunoglobulin G reactive to the PTHrP(102-111) or PTHrP(110-119) peptide was frequently detected in the plasma of prostate cancer patients, suggesting that the PTHrP(102-111) peptide is able to elicit cellular and humoral immune responses in cancer patients. These results indicate that the PTHrP could be a promising target molecule for specific immunotherapy of HLA-A24(+) prostate cancer patients with metastases.

Identification of epidermal growth factor receptor-derived peptides immunogenic for HLA-A2(+) cancer patients.

Epidermal growth factor receptor (EGFR) is one of the most appropriate target molecules for cancer therapy because of its relatively high expression in about one-third of all epithelial cancers in correlation with neoplasmic progression. With respect to EGFR-targeted therapies, antibodies and tyrosine-kinase inhibitors have been intensively studied, a novel EGFR-tyrosine-kinase inhibitor ZD1839 has been approved as an anticancer drug, and many other agents are now under clinical trial. In addition, cytotoxic T lymphocyte (CTL)-directed epitope peptides could be another class of compounds useful in EGFR-targeted therapies. However, there is presently no information on CTL-directed peptides of EGFR. Therefore, from the viewpoint of development of peptide-based cancer therapy, this study was intended to determine the EGFR-derived peptides recognised by both cellular and humoral immunities in HLA-A2(+) epithelial cancer patients. We herein report finding of two such types of EGFR-derived peptides at position 479-488 and 1138-1147, both of which were recognised by the majority of patients' sera (IgG), and also possessed the ability to induce HLA-A2-restricted peptide-specific CTLs against EGFR-positive tumour cells in peripheral blood mononuclear cells (PBMCs) of epithelial cancer patients. These results may provide a scientific basis for the development of EGFR-based immunotherapy for HLA-A2(+) cancer patients.

TCR gamma delta + T cells in peripheral blood of patients with adult Still's disease.

OBJECTIVE: Adult Still's disease, a systemic inflammatory disorder of unknown etiology, shows few specific laboratory markers and histological features. We investigated T cell subsets in peripheral blood lymphocytes (PBL) of patients with adult Still's disease to elucidate immunological features of the disease. METHODS: We studied T cell subsets in PBL of 12 patients with adult Still's disease by flow cytometric analysis. T cell subsets were also investigated for more than 6 months in PBL of 3 patients with adult Still's disease. RESULTS: Both the percentage and absolute number of T cell receptor gamma delta positive (TCR gamma delta +) T cells in active adult Still's disease (n = 6) were significantly (p < 0.05) higher than those in inactive adult Still's disease (n = 6), inactive rheumatoid arthritis (n = 8), or healthy controls (n = 20). An increase of TCR gamma delta + T cells was observed in 5 of 6 patients with adult Still's disease at the active phase. TCR gamma delta + T cells also increased for a considerable period in all the patients tested. In contrast, there were no significant differences in the other T cell subsets (CD3, CD4, CD8, TCR alpha beta) between all the patients and healthy donors. Levels of TCR gamma delta + T cells in PBL correlated well with those of serum ferritin and C-reactive protein in one of the 3 patients whose PBL could be serially investigated. These increased TCR gamma delta + T cells mostly consisted of a V gamma 9/V delta 2 subset. CONCLUSION: TCR gamma delta + T cells in PBL are significantly increased in the active phase in patients with adult Still's disease.

Collision of malignant lymphoma and multiple early adenocarcinomas of the stomach.

An unusual case of coexisting malignant lymphoma and adenocarcinoma of the stomach is described. A 61-year-old man with weight loss, malaise, and tarry stool demonstrated diffuse lymphoma, large-cell type, and two early gastric carcinomas. Each of the two early carcinomas collided with malignant lymphoma, respectively. Two histologically different tumors were precisely diagnosed preoperatively in this case. Frequent endoscopy with biopsies from various sites of the lesion is important in achieving a correct diagnosis.

The effects of excess amino acids on maintenance of pregnancy and fetal growth in rats.

The effects of diets, each with an excess of one essential amino acid, on the maintenance of pregnancy and fetal growth were investigated in rats. Rats were fed on 6% casein diet containing 5% threonine, methionine, valine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, or lysine from day 1 to day 14 or 21 of pregnancy. Excess methionine and leucine diets resulted in complete and 80% loss of fetuses, respectively. This fetal wastage was prevented by daily injection of 0.5 microgram of estrone and 4 mg of progesterone. Judging from the total food consumptions and body weight gains during pregnancy, methionine had the most severe effects, followed in order by leucine, tryptophan, valine, lysine, isoleucine, threonine, phenylalanine, and tyrosine. The weights of fetuses in the excess amino acid groups were significantly lower than those in the respective pair-fed controls. Excess aromatic amino acids caused growth retardation of fetal brain, although the levels of free tyrosine and phenylalanine in fetal brain were not high. The concentrations of free methionine and threonine were markedly elevated in the maternal plasma when these amino acids were fed in excess, but those of other amino acids were not increased appreciably by excess amounts in the diet. Changes in the maternal plasma levels of individual amino acids other than those in excess in the diet were small. On the contrary, the levels of not only the excess amino acids but also of other amino acids in fetal brains were appreciably elevated by these diets. These findings suggest that the blood-brain barrier is immature and that the synthesis of proteins in fetal brain is impaired by excess amino acids in the mothers. The importance of experiments on diets with excess of single amino acids in pregnant animals is discussed in connection with studies on inborn errors of amino acid metabolism.