Prospect of Endoscopic Mucosal Resection for Early Gastric Cancer: Our Devices in Insulated‐Tip Electrosurgical Knife Method

In Kobe University Hospital, a new method for endoscopic mucosal resection (EMR) using insulated‐tip electrosurgical knife (IT‐EMR) for early gastric cancer (EGC) was introduced from November 2001. To achieve an effective and safe IT‐EMR procedure, we use a high‐frequency surgical unit for cutting and coagulation (ERBOTOM ICC 200) with automatically controlled cutting mode (ENDOCUT). In this study, we show not only our results of IT‐EMR for EGC in comparison with those of the conventional strip biopsy method, but also the optimal conditions for the apparatus of a high‐frequency surgical unit to prevent complications such as bleeding and perforation.     

Comparison of inhalation inductions with xenon and sevoflurane

Background: Xenon is an odorless gas with low blood-gas solubility coefficient and without occupational and environmental hazards. This investigation was performed to evaluate the speed of induction, and respiratory and cardiovascular reactions to inhalation induction with xenon compared to an equianesthetic concentration of sevoflurane.
Results: Compared to equianesthetic sevoflurane, xenon produced a faster induction of anesthesia (14759 versus 71221 s, respectively) with smaller decreases in respiratory rate, tidal volume and minute ventilation. Both agents showed comparable cardiovascular stability and oxygen saturation during induction. One patient in the sevoflurane group had breath-holding and movements of extremities and another had only breath-holding. No patients in the xenon group experienced any complications.
Conclusion: Xenon produced a faster induction of anesthesia without any complications than sevoflurane. Xenon had smaller decreases in tidal volume and respiratory rate during induction than sevoflurane. Xenon might offer an alternative to sevoflurane for an inhalation induction.
Method Twenty-four adult ASA 1–2 patients premedicated with 0.05 mg/kg of midazolam were instructed to take vital capacity breaths of 1 minimum alveolar concentration (MAC) of either xenon or sevoflurane until they lost consciousness. Induction time, total ventilatory volume, tidal volume, respiratory rate, minute ventilation, end-tidal MAC fraction, cardiovascular parameters and oxygen saturation were recorded. The patients were interviewed on the following day to evaluate their acceptability rating of the inhalation inductions.     

Oxygenated and reoxygenated tumors show better local control in radiation therapy for cervical cancer

The presence of hypoxic cells is one of the major factors affecting resistance against radiation therapy. In the clinical setting, little information exists as to the relationship between intratumoral oxygen partial pressure (pO(2)) and outcome. This study involved 30 consecutive patients with cervical cancer, who were treated with a combination of external and high-dose rate intracavitary irradiation. The pO(2) was measured before radiation therapy and at 9 Gy, using a needle-type polarographic oxygen electrode. The mean intratumoral pO(2) before radiation therapy was 17.3 +/- 10.8 mm Hg. The 3-year local control rates of patients with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg before radiation therapy were 52% and 100%, respectively, representing a significant difference (P= 0.035). At 9 Gy, mean intratumoral pO(2) was 23.6 +/- 9.1 mm Hg, a significant increase compared to the value before radiation therapy (P= 0.006). The 3-year local control rates of tumors with pO(2)< or = 20 mm Hg and pO(2) > 20 mm Hg at 9 Gy were 35% and 93%, respectively, representing a significant difference (P= 0.001). The significantly better local control for oxygenated tumors at 9 Gy as well as before radiation therapy indicated that the oxygen effect and reoxygenation by radiation played an important role in local control in radiation therapy for cervical cancer.     

Localization and expression of chondromodulin-I in the rat cornea

The localization and expression in the rat cornea of chondromodulin-I (ChM-I), an inhibitory angiogenesis factor, were examined by immunohistochemistry, Western blot analysis, ribonuclease protection assay, and real-time PCR assay. We found immunoreactivity for ChM-I in the epithelial layer but not the stromal layer or endothelial layer in the cornea, in addition to the positive ChM-I immunoreactivity in other sites in the eye such as the sclera, retina, and ciliary body. The ChM-I immunoreactivity was most intense at the outside of the basal cells and in their cytoplasm while the intensity of the immunoreactivity decreased gradually from the wing cells to the superficial cells in the corneal epithelial layer. No reactivity however, was detected in the Bowman's membrane or conjunctival epithelial cells which had continuity with the corneal epithelial cells. The expression of ChM-I mRNA was demonstrated in the cornea at one-third less intensity than that in the sclera with choroids and retinal pigment epithelium by ribonuclease protection assay and real-time PCR. ChM-I in the corneal epithelial layer may prevent neovascularization and maintain avascularity in the cornea.     

Fc receptor-mediated accumulation of macrophages in crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody administration in WKY rats

Anti-glomerular basement membrane (GBM) glomerulonephritis induced in WKY rats is characterized by glomerular accumulation of CD8(+) T cells and monocytes/macrophages, followed by crescent formation. The mechanism of leukocyte accumulation after antibody binding to GBM is still unclear. To unveil an involvement of Fcgamma receptors (FcgammaR) in leukocytes recruitment we examined the expression of FcgammaR in glomeruli and the effects of the administration of F(ab')(2) fragment of anti-GBM antibody or FcgammaR blocking on the initiation and progression of this model. A gradual increase of FcgammaR mRNA expression in glomeruli during the time course of disease suggested their significance in the development of glomerulonephritis. Glomerular lesions and proteinuria were induced only in rats injected with intact IgG of anti-GBM antibody, but not with the F(ab')(2) fragment. In vivo blocking of FcgammaR by administering heat-aggregated IgG led to the decrease of mRNA expression for all types of FcgammaR (types 1, 2 and 3) and a significant amelioration of glomerulonephritis manifestations. By flow cytometry and immunohistochemistry FcgammaR2-expressing cells in glomeruli were identified as macrophages, but not CD8(+) T cells. The expression of FcgammaR1 and 3 was significantly decreased, and that of FcgammaR2 became undetectable in CD8(+) T cell-depleted rats. Thus, CD8(+) T cells may stimulate FcgammaR expression on macrophages, contributing to their glomerular accumulation and injury. These studies provide direct evidence for a crucial involvement of IgG Fc-FcgammaR interaction in glomerular recruitment of macrophages and following induction of anti-GBM glomerulonephritis in WKY rats.     

The Role of Polymorphonuclear Leukocytes in Rat Chronic Serum Sickness-type Nephritis

In order to investigate the role of polymorphonuclear leukocytes (PMN) in the distribution of antigen in various organs and in the development of nephritis, chronic serum sickness type nephritis was induced in both anti rat PMN rabbit serum (APS) treated and normal rabbit serum (NRS) treated rats by preimmunization with bovine serum albumin (BSA) and subsequent daily intravenous administration of BSA for 4 weeks. Kinetic studies using radiolabeled BSA showed that accumulation of BSA after the first intravenous administration was reduced by APS treatment in the liver, lungs and spleen and increased in the circulation, but was not affected in the kidneys and glomeruli. Histological studies supported the above findings. After 4 weeks of BSA administration, the BSA accumulation in the kidneys and glomeruli was significantly less in APS treated rats than in NRS treated ones, while amounts of BSA in the circulation and other organs were not different between the two groups. Furthermore, APS treatment reduced proteinuria, PMN infiltration and IC deposition in the glomeruli. These observations indicate that PMN play a partial role in IC deposition in the glomerular capillary walls and subsequent destruction of glomerular permeability in chronic serum sickness-type nephritis. Acta Pathol Jpn 39 : 619-629, 1989.     

Differential Sensitivities of Purified Human Eosinophils and Neutrophils to Defined Chemotaxins

Functions of eosinophils and neutrophils isolated from normal human blood were determined by measuring chemotactic migration and release of beta-glucuronidase. Four well-characterized chemotaxins, the complement fragment C5a, formyl-methionyl-leucyl-phenylalanine (FMLP), platelet-activating factor (PAF), and leukotriene B4 (LTB4) were used as stimuli. Neutrophils showed remarkable chemotactic responses to all four chemotaxins. In contrast, eosinophils showed a significant chemotactic response to C5a and PAF, but only weak responses to FMLP and LTB4. Using these chemotaxins we found the following order of chemotactic potency (maximal number of migrated cells): C5a = LTB4 greater than FMLP greater than PAF for neutrophils and PAF = C5a greater than LTB4 = FMLP for eosinophils. Neutrophils elicited a significant beta-glucuronidase release when stimulated by C5a and FMLP, whereas only small amounts were released with PAF and LTB4. On the other hand, an amount of beta-glucuronidase released from eosinophils comparable to that from neutrophils was elicited only with C5a. FMLP, LTB4, and PAF caused the release of small percentages of beta-glucuronidase. The important cellular functions of eosinophils and neutrophils, chemotaxis and enzyme release, are thought to be controlled by differential responsiveness to stimuli.     

BOVINE SERUM ALBUMIN (BSA) NEPHRITIS IN RATS IV. A SEQUENTIAL EVALUATION OF MONONUCLEAR PHAGOCYTE SYSTEM (MPS) FUNCTION

A clearance kinetic study of intravenously administered ¹²⁵I-labeled aggregated human IgG (¹²⁵I-AHIgG) from the circulation and its distribution in various organs was performed weekly during the course in a model of experimental immune complex glomerulonephritis which was induced in rats immunized 8 weeks previously with 6 times a week administration of 2 mg of bovine serum albumin (BSA) for 4 weeks from week 8 to 12. The removal rates of the injected ¹²⁵I-AHIgG from the circulation were retarded in nonproteinuric rats of week 9 and 10, at almost every checked point (p-value was <0.01). The clearance in those rats with severe proteinuria returned to the level of the control and of rats in week 8. The distribution of ¹²⁵I-AHIgG in the liver 4 hours after the administration revealed a considerable decrease in non-overt proteinuric rats of weeks 9, 10, and 11. A similar tendency of decreasing depositions of the radioactivity was shown in the spleen at each 4 hours. In contrast, the uptakes in the kidney and lung at the final week of 12 were larger. Delayed clearance from the circulation and a decreasing handle of the injected macromolecule in the liver and possibly in the spleen may suggest the presence of some impairment of the MPS function in the course of this experimental glomerulonephritis.     

Effect of hypothermia on the in vitro potencies of neuromuscular blocking agents and on their antagonism by neostigmine

The effect of temperature on the potencies of neuromuscularblocking agents remains unclear. This study was undertaken toexamine the effects of different neuromuscular blocking agentsat 37 and 27 °C at a constant carbon dioxide content ( statprinciple). The effect of neostigmine 1 µmol litre^–1induced antagonism of these agents was also investigated. Phrenicnerve-hemidiaphragm preparations of rats were mounted in modifiedKrebs solution, maintained at 37 CC and aerated with a 5% carbondioxide-95% oxygen gas mixture, and at 27 °C with 4% carbondioxide to maintain the carbon dioxide content of the solutionconstant. Phrenic nerves were stimulated with 0.1 -Hz supra-maximalimpulses of 0.2-ms duration and the elicited tension of thediaphragm recorded. The potencies of the steroidal neuromuscularblocking agents (rocuronium, vecuronium, pancuronium and pipecuronium)increased significantly at 27 °C (P<0.05), while thepotencies of the benzyliso-quinolinium agents (tubocurarineand dimethyl-tubocurarine) did not change. Neostigmine-inducedantagonism of the steroidal agents did not differ significantlybetween each other but differed significantly from the benzylisoquinoliniumagents (P<0.05) at both temperatures. The ratios of IC₅₀(inhibitory concentration, 50%) with and without neostigmineat hypothermia were slightly higher for the steroidal agents,indicating slight enhancement of antagonism by neostigmine at27 °C. In contrast, the ratios were significantly greaterat 27 °C (P<0.05) for isoquinolinium agents, implyingsignificant enhancement of antagonism. Our results indicatethat at 27 °C the potency of all steroidal agents increasedand neostigmine-induced antagonism was slightly enhanced. Withthe isoquinolinium agents, hypothermia caused no change in potencyalthough neostigmine-induced antagonism was enhanced significantly.These findings suggest that the relative effects of steroidaland isoquinolinium agents on the neuromuscular junction aredifferent or that they have a different mechanism of actionon the neuromuscular junction.     

Expression of the TGF-β–ALK-1 Pathway in Dura and the Outer Membrane of Chronic Subdural Hematomas

Neovascularization of the outer membrane plays a critical role in the development and enlargement of chronic subdural hematomas (CSHs) and vascular endothelial growth factor (VEGF) may promote their progression. However, the precise mechanisms remain to be determined. We focused on the signaling pathway upstream of VEGF, transforming growth factor β (TGF-β), and activin receptor-like kinase 1 (ALK-1) to identify the mechanisms underlying the neovascularization of the outer membrane of CSH. Retrospective comparative study was conducted on 15 consecutive patients diagnosed as CSH with burr-hole drainage. Dura and the outer membrane were collected. We immunohistochemically examined the expression of VEGF, integrin-α, TGF-β, and ALK-1 on the outer membrane and dura of CSH and compared our findings with control samples and the signal intensity of hematomas on computed tomography (CT) scans. VEGF and integrin-α expression was markedly up-regulated in both the dura and outer membrane of CSH, the expression of TGF-β and ALK-1 in the dura was slightly increased in the dura and markedly up-regulated in the outer membrane. There was no significant correlation between their expression and CT density. Here we first report the expression of TGF-β and ALK-1 in the outer membrane and dura mater of CSH. We suggest that the TGF-β–ALK-1 pathway and VEGF affect neovascularization and the progression of CSH.