Analysis of the T cell receptor V beta repertoire in 2,4,6-trinitrobenzenesulfonic acid induced colitis in mice

The aim of this study was to analyze which types of T cells are at work and the specific nature of their response, using a mouse 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis model. The response of T cells to TNBS was analyzed by anti-TNBS mixed-lymphocyte reaction. T cell clones were established by limiting dilution. Phenotypes and T cell receptor (TCR) V beta of T cells were analyzed by flow cytometry. Colitis was induced by administration of TNBS enemas, and lamina propria lymphocytes were isolated and analyzed. The proliferative responses to TNBS of spleen T cells were partially inhibited by the addition of antimouse CD4 or CD8 antibodies to the mixed-lymphocyte culture. Conversely, these were inhibited by the addition of both antibodies. Flow cytometric analysis showed that TCR V beta 14 T cells specifically increased in the CD8+ T cell population. We established CD8+ TCR V beta 14 T cell clones which were TNBS reactive and self-restricted. Investigation using lamina propria lymphocytes in TNBS-induced colitis revealed that the rate of CD8+ TCR V beta 14 T cells changed with histological inflammatory activity which also attained a peak on day 5 following enema administration. Both CD4+ and CD8+ T cell subsets responded to TNBS, and the rate of CD8+ TCR V beta 14 T cells changed with histological inflammatory activity in TNBS-induced colitis.     

The role of protein kinase C isoforms in cell proliferation and apoptosis

Protein kinase C (PKC) was first described as a calcium-activated, phospholipid-dependent serine/threonine protein kinase 22 years ago, and it has since been studied extensively as a second messenger transducing diverse signals regarding cell proliferation, activation of cellular function, differentiation, and even apoptosis. Because PKC consists of at least 11 isoforms, with possibly different biological properties, it is necessary to reevaluate its known functions as functions of each isoform. Recent studies have revealed that several other lipid metabolites generated by signal-induced hydrolysis of membrane phospholipids, such as ceramide and phosphatidylinositol-3,4,5-triphosphate, may also have the potential to mediate external signals. Here we describe the roles of PKC isoforms in cell proliferation and apoptosis, particularly in relation to other lipid metabolites.     

Suicide inactivation of androstenedione aromatase in human placenta by fluoroethindrone (10 beta-fluoro-17 alpha-ethynyl-19-nortestosterone)

The inhibitory effects of androstenedione aromatase activity in human placenta using fluoroethindrone (10 beta-fluoro-17 alpha-ethynyl-19-nortestosterone), which is a derivative of norethindrone (17 alpha-ethynyl-19-nortestosterone, ENT) and, unlike ENT, is considered to be refractory to aromatization, was investigated in this study. When fluoroethindrone was added to the placental microsomes in the presence of NADPH, androstenedione aromatase activity in the placental microsomes was decreased time dependently and dose-dependently by fluoroethindrone compared with the samples without NADPH. This finding suggests that fluoroethindrone acts as a suicide substrate for androstenedione aromatase in human placenta.     

Prognostic significance of macroscopic serosal invasion in advanced gastric cancer

BACKGROUND/AIMS: Although histologic invasion of the gastric serosa is associated with poor prognosis in patients with gastric cancer, the prognostic significance of macroscopic invasion of the serosa is not clear. The aim of this study was to clarify the clinical significance of macroscopic serosal invasion in advanced gastric cancer. METHODOLOGY: Clinicopathologic data from 257 patients who underwent curative gastrectomy for advanced gastric cancer was analyzed to evaluate the prognostic significance of macroscopic serosal invasion. On the basis of macroscopic findings, tumors were classified as SO, negative serosal invasion; S1, positive serosal invasion; or S2, invasion extending to the adjacent organ. We also examined the relation between the extent of macroscopic serosal invasion (SO, S1, S2) and volumetric shape of cancerous invasion (funnel, column, and mountain types). RESULTS: In comparison with SO tumors, S1 and S2 tumors were significantly more likely to be more than 5cm in diameter and show histologically serosal invasion. Volumetric analysis showed that S1 and S2 tumors were more frequently column- or mountain-shaped than were SO tumors. The 5-year survival rate differed significantly between patients with SO, S1, and S2 tumors (88% us. 65% vs. 18%, P<0.01). Multivariate analysis indicated that macroscopic serosal invasion was an independent prognostic factor. CONCLUSIONS: Macroscopic serosal invasion is associated with extensive cancerous invasion of the deep gastric wall. The presence of macroscopic serosal invasion indicates advanced tumor progression and poor prognosis for patients with advanced gastric cancer. Clinically, knowledge of the extent of macroscopic serosal invasion is helpful in planning adjuvant chemotherapy.     

Dose requirement for caudal anesthesia in pediatric patient

A series of 305 infants and children between 1 day to 14 years of age were operated upon using caudal anesthesia. We used 1% mepivacaine 1.2 ml.kg-1 to obtain a level of anesthesia above T10, 1.0 ml.kg-1 above L1, and 0.8 ml.kg-1 above S. Complete failure occurred in 4.3% of patients. We investigated the blood concentration of mepivacaine in 17 patients, and it ranged from 0.5 microgram.ml-1 to 5.0 micrograms.ml-1. In a two month old infant, weighing 6.7 kg, apnea and bradycardia occurred. This was managed by tracheal intubation and controlled ventilation. But there were no other severe complications. We also investigated the distance between C7 and sacral hiatus (D) in each case. The coefficients of correlation between D and height is 0.97, and high correlation existed also between D and body weight (r = 0.93). This confirms that body weight can be used as a parameter to determine the dose of local anesthetic agent. We conclude that this technique is a safe, reliable and simple way to produce surgical analgesia in infants and children.     

The inductive effects of progestogens on aromatase activity in stromal cells of human uterine endometrium

Aromatase activity for androstenedione was measured in stromal cells of human uterine endometrium throughout the menstrual cycle. The effect of progestogen on aromatase activity was also examined in the endometrial stromal cells. Aromatase activity tended to be high in the proliferative cells compared to the secretory cells. Moreover, its enzyme activity was enhanced at the concentration of 0.1 or 1.0 microM of medroxyprogesterone acetate (MPA) and norethindrone (ENT) in all phases of menstrual cycle. MPA stimulated aromatase activity in the stromal cells more strongly than did ENT. These results may suggest that although aromatase in uterine endometrium is not regarded to be so much influenced by endogenous progesterone during menstruation, the increase of aromatase activity by progestogen added lead to the more differentiated endometrium.