Shohei Ogoshi

HLA-DR antigen- and S-100 protein-positive dendritic cells in esophageal squamous cell carcinoma— Their distribution in relation to prognosis

SummaryThe distribution of immunohistochemically labeled HLA-DR antigen- and S-100 protein-positive dendritic cell (DR+ DC and S100+ DC) was investigated in 59 human esophageal squamous cell carcinomas (SCCs). A dense infiltration of both DR+DC and S100+DC was detected in 11, only DR+ DC in two, and only S100+ DC in one. In the remaining 45 tumors infiltrating DC were sparse. By means of double immunostaining or the miroor section method, three different types of DC, namely S-100-negative and HLA-DR-positive DC(S100− DR+ DC), S-100-positive and HLA-DR-negative DC(S100+ DR− DC) and double-positive DC (S100+ DR+ DC) were clearly identified. With regard to postoperative survival, these patients with tumours in which there was a dense infiltration of DR+ DCs and/or S100+ DCs showed a significantly better survival rate than those in which DC were sparse (DR+ DCs—P<0.001; S100+ DCs—P<0.01). These results indicate that DC infiltration may be a prognostic factor in esophageal SCCs.

Complement Activation in Cardiopulmonary Bypass, with Special Reference to Anaphylatoxin Production in Membrane and Bubble Oxygenators

Complement activation by cardiopulmonary bypass (CPB) was studied in 82 patients divided into membrane (MOG) and bubble oxygenator groups (BOG). The influence of primed homologous to circulating autologous blood volume (H/A) ratio was also evaluated. C4a increased very slowly during CPB in both groups, maintaining slightly higher levels in the BOG than in the MOG, with the exception of a marked initial rise in the BOG with a high H/A ratio (greater than or equal to 20%). Anaphylatoxin C3a levels increased more steeply in the BOG than in the MOG. An obvious rise in anaphylatoxin C5a production was observed in the BOG alone. The influence of high H/A ratio perfusion on complement activation was milder in the MOG than in the BOG. In 20 monkeys (Macaca fascicularis), continuous intraaortic infusion with bubbled autologous blood increased C4a and C3a levels, while autologous blood extracorporeally contacted with nylon increased C3a levels alone. In vitro studies revealed that human immunoglobulin fractions denatured by oxygen bubbling produced C4a, C3a, and C5a in a dose-dependent manner, although human albumin treated identically as human immunoglobulin did not produce these complements. It was thus inferred that (1) during CPB, complement is predominantly activated via the classical pathway in the BOG and via the alternative pathway in the MOG; (2) higher anaphylatoxin levels in the BOG than in the MOG are related to mode and grade of blood trauma; (3) anaphylatoxin level differences in both groups tend to increase with high H/A perfusion; and (4) immunoglobulin-free sera may reduced classical pathway activation.

Arginine-Supplemented Diet Decreases Expression of Inflammatory Cytokines and Improves Survival in Burned Rats

BACKGROUND We examined whether the expression of inflammatory cytokines in organs was influenced by the enteral diet supplemented with arginine in burned rats. METHODS Male Wistar rats weighing about 200 g underwent catheter jejunostomy and received scald burns covering 30% of the whole-body surface area. Animals were divided into two groups: a control group (no supplemental arginine, n = 12) and an arginine group (supplemental arginine: 7.7 g/L, n = 10), which continuously received total enteral nutrition for 7 days (250 kcal/kg/d, 1.72 gN/kg/d). The following were measured after the experiment: (1) messenger RNA (mRNA) expression of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-1beta (IL-1beta), and IL-6 in the spleen, thymus, lung, and liver by a semiquantitative reverse transcription-polymerase chain reaction method, (2) inflammatory cytokines in the plasma and supernatant of cultured splenic lymphocytes by enzyme-linked immunosorbant assay, (3) nitric oxide (NO) product, NO2-/NO3-, in the plasma and supernatant of cultured splenic lymphocytes by the Griess method, and (4) survival rate by the Kaplan-Meier method. RESULTS The mRNA expression of TNF-alpha was significantly decreased in the spleen and lung (p < .01, p < .05), IFN-gamma in the lung (p < .05), IL-1beta in the spleen (p < .05), and IL-6 in the thymus and liver (p < .05, p < .05) in the arginine group when compared with the control group. The production of TNF-alpha by splenic lymphocytes was suppressed in the arginine group in both concanavalin A (Con A)-treated and -untreated cultures (p < .01, p < .05). The production of IFN-gamma by splenic lymphocytes treated with Con A was suppressed in the arginine group (p < .05). The NO product in the supernatant without Con A was increased in the arginine group (p < .05). The mortality rate of the arginine group (0%) was lower than that in the control group (33.3%) on day 7 after the burn injury (p < .05). CONCLUSIONS The data suggest that dietary arginine supplementation decreases the mRNA expression of inflammatory cytokines in organs and improves the survival rate after thermal injury.

Effect of nucleotide and nucleoside mixture on rats given total parenteral nutrition after 70% hepatectomy.

After partial hepatectomy rats were used as a model of patients with liver tumor after extensive hepatectomy. Supplementation of a nucleotide and nucleoside mixture to the total parenteral nutrition solution in rats after 70% hepatectomy resulted in earlier restoration of the nitrogen balance in the first 3 days than the solution without this supplementation. This supplementation had no unfavorable effects on the compositions of the blood and urine, and particularly the metabolites of nucleic acids such as uric acid, beta-alanine, and beta-aminoisobutyric acid. A suitable ratio of nucleotides plus nucleoside to amino acids was tentatively concluded to be 1:2 g N with a calorie supply of 400 kcal.

Effects of total parenteral nutrition with nucleoside and nucleotide mixture on D-galactosamine-induced liver injury in rats.

The effect of a nucleoside-nucleotide mixture on liver injury of rats induced by D-galactosamine was studied by examining changes in function and histopathology of the liver. Animals with liver damage received total parenteral nutrition with glucose and amino acids supplemented with a nucleoside-nucleotide mixture containing inosine, cytidine, GMP, uridine and thymidine, or with uridine which inhibits galactosamine injury, or with liver cell extract containing flavin adenine dinucleotide and nucleic acid derivatives. As control, animals with liver damage received total parenteral nutrition with glucose and amino acids only. The serum GOT and GPT concentrations were significantly lower in the group supplemented with nucleoside-nucleotide mixture than those in other groups. A large dose (1.2 g/kg) of uridine inhibited liver injury, but a lower dose (0.14 g/kg) did not have any effect, whereas nucleoside-nucleotide mixture containing the same amount of uridine inhibited the injury. Liver cell extract also did not improve liver function. Thus infusion of a physiological and balanced mixture of nucleosides or nucleotides may improve liver function in rats with liver injury.

Effects of Dietary Arginine Supplementation on Protein Turnover and Tissue Protein Synthesis in Scald-Burn Rats

We assessed the effects of dietary arginine supplementation on protein turnover and organ protein synthesis in burned rats. Male Wistar rats weighing about 200 g underwent catheter jejunostomy and received scald burns covering 30% of the whole-body surface area. Animals were divided into a control group (n = 9) and an arginine group (n = 9) and continuously received total enteral nutrition for 7 d (250 kcal.kg-1.d-1, 1.72 gN.kg-1.d-1). Changes in body weight, plasma total protein, plasma albumin, urinary excretion of polyamines, nitrogen balance, whole-body protein kinetics, and tissue protein synthesis rates were determined. Whole-body protein kinetics and tissue fractional protein synthetic rates (Ks, percent/d) were estimated using a 24-h constant enteral infusion of 15N glycine on the last day. The changes in body weight were not different between the control and arginine groups. The urinary excretion of polyamines was higher in the arginine group than in the control group (P < 0.01). Burned rats enterally fed arginine-supplemented diet yielded significantly greater cumulative and daily nitrogen balance on days 3 and 5 than those fed a control diet (cumulative, P < 0.05; day 3, P < 0.01; day 5, P < 0.01). Whole-body protein turnover rate was significantly elevated in the arginine group as compared to that in the control group (P < 0.05). The Ks of rectus abdominis muscles were significantly increased in the arginine group in comparison to the control group (P < 0.01). We have shown that dietary arginine supplementation improved protein anabolism and attenuated muscle protein catabolism after thermal injury.

Assessment of internal thoracic artery graft with intraoperative color doppler ultrasonography

BACKGROUND Intraoperative ultrasonography has the potential to provide anatomic and functional information about internal thoracic artery (ITA) graft, but this potential has been hindered by the relatively large standard probe. In this study, we used a color Doppler microprobe to evaluate ITA grafts. METHODS The subjects were 15 consecutive patients who underwent elective coronary artery bypass grafting either with cardiopulmonary bypass (n = 14) or without (n = 1). All patients underwent anastomosis of the left ITA to the left anterior descending artery. The ITA graft was assessed before the chest was closed, with the microprobe placed directly on the graft. RESULTS A good-quality color Doppler image of the ITA graft was easily obtained in all 15 patients within a few minutes. The ITA graft function was assessed by analyzing the shape of the pulsed Doppler wave. All ITA grafts were patent, and the mean graft diameter was 1.8 +/- 0.04 mm. The peak systolic velocity, peak diastolic velocity, and mean velocity were 52.0 +/- 14.9 cm/s, 58.3 +/- 22.4 cm/s, and 36.5 +/- 10.9 cm/s, respectively. The ratio of peak diastolic velocity to peak systolic velocity was 1.24 +/- 0.66. The ITA graft seemed to function well when the biphasic diastolic predominant flow appeared. The mean blood flow was 55.1 +/- 22.0 mL/min. CONCLUSIONS Intraoperative ultrasonography using the microprobe provides adequate anatomic and hemodynamic information regarding ITA grafts. As the Doppler flow evaluation has high sensitivity and specificity, we suggest that intraoperative ultrasonography is useful for the assessment of these grafts.

Intraoperative detection of embedded coronary arteries in MIDCAB using a color Doppler microprobe

Intraoperative detection of deeply embedded coronary arteries is difficult, especially in minimally invasive coronary artery bypass grafts. This report describes an effective method to identify embedded coronary arteries by using a color Doppler microprobe. Five embedded left anterior descending coronary arteries were successfully identified by intraoperative ultrasonography. We believe that the color Doppler microprobe is helpful for surgeons in this difficult situation.

Quenching the Effects of L-Arginine on Free Radical Injury in Cultured Cardiomyocytes

Neutrophil activation and oxygen-derived free radical formation have been implicated in cardiac ischemiareperfusion injury. To elucidate the mechanism of ischemiareperfusion injury, we thus determined the effect of the nitric oxide (NO) precursorl-arginine on the free radical injury of cultured cardiomyocytes which were obtained from patients undergoing corrective surgery for tetralogy of Fallot. Free radicals were generated from hypoxanthine via xanthine oxidase, and the cellular changes were determined microscopically.All concentrations of L-arginine (0.5 to 3 mM) prolonged the myocyte survival time compared to the control group, with 0.5 mMl-arginine increasing the survival time to the greatest extent. Cellular susceptibility to free radical injury was the lowest with 0.5 mMl-arginine. Further experiments were performed with 0.5 mMl-arginine plus 100 mM or 1 000 mM of the NO synthase (NOS) inhibitorNG-nitro-l-arginine methylester (l-NAME) to determine whether or not the effects of L-arginine are mediated through the NO pathway. The survival time for the cells treated with a concentration ofl-NAME was shorter than for the cells treated with 0.5 mMl-arginine alone. These results suggest thatl-arginine acts through the NO-dependent pathway. In conclusion, our findings thus confirmed the quenching effects of NO on free radical injury in cultured cardiomyocytes.

Route of Feeding Influences the Production and Expression of Tumor Necrosis Factor α in Burned Rats

Abstract The effect of nutritional route on tumor necrosis factor α (TNF-α) production in burned rats was examined. Scald burns covering about 30% of the whole body surface area were inflicted on 43 male Wistar rats weighing about 200 g. The animals were divided into three groups: CHOW (n = 10), total parenteral nutrition (TPN) (n = 22), and total enteral nutrition (TEN) (n = 11), continuously given a chow diet, TPN solution, or an enteral diet, respectively, for 7 days after the burn injury. The rate of detection of TNF-α in plasma on day 7 was significantly higher in the TPN group than in the CHOW or TEN groups. The messenger RNA (mRNA) expression of TNF-α was significantly increased in the spleen, lungs, liver, and ileum of the rats receiving TPN compared with the CHOW and TEN rats. On the other hand, the expression of TNF-α mRNA was markedly decreased in the thymus of the TPN group compared with the CHOW group. The mortality rate in the TPN group (63.6%) was higher than that in the CHOW (0.0%) or TEN (27.3%) groups on day 7 after burn injury. These data suggest that TPN increases the expression of TNF-α mRNA in organ tissues and systemic TNF-α production, and reduces the survival rate of rats after thermal injury, but TEN does not.