Initial steroid bolus injection promotes vigorous CD8+ alloreactive responses toward early graft acceptance immediately after liver transplantation in humans.

We have found that steroid bolus withdrawal prior to graft reperfusion increased the incidence of acute cellular rejection (ACR). This study aims to clarify how initial steroid bolus (ISB) injection at reperfusion influences the kinetics of CD8(+) alloreactive immune responses immediately after living donor liver transplantation (LDLT). A total of 49 hepatitis C virus (HCV)-infected recipients were classified into 3 groups according to hierarchical clustering by preoperative CD8(+)CD45 isoforms. The naive T cell proportion was considerably higher in Group I than in Groups II and III, whereas Group II recipients had the highest effector memory (EM) T cells and Group III the highest effector T cells. The frequency of ACR was significantly higher in recipients without ISB than in those with ISB. In particular, the ACR rates were the highest in Group II without ISB. Following ISB, the proportion of effector T cells was promptly upregulated within 6 hours after graft reperfusion, simultaneously with the upregulation of CD27(-)CD28(-) subsets, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha and perforin expression, which significantly correlated with increasing interleukin (IL)-12 receptor beta 1 cells. These were then downregulated to below preoperative levels by tacrolimus (Tac) administered at 24 hours. These changes did not occur in the absence of ISB. In Group II without ISB, the downregulation of IL-12Rbeta1(+) cells was the greatest, consistent with the highest rates of ACR and mortality (60%). In conclusion, ISB must be done in place, especially in Group II with preexisting high EM T cells, to enable the development of early allograft acceptance.     

Measures of Explained Variation for a Regression Model Used in Survival Analysis

This paper describes a measure of explained variation (MEV) of survival times for a given regression model used in survival analysis. It quantifies the predictive power of a set of prognostic factors in the model, and therefore provides useful information for more precise prediction of patient prognosis, and for designing randomized clinical trials with the capability of determining treatment effects. The MEV defined in this article is asymptotically derived from the squared product-moment correlation; it can be interpreted as an adaptation of the multiple correlation coefficient for the normal linear model to the survival time regression model. Monte-Carlo simulations are performed to investigate the statistical behavior of the proposed MEV. The MEV is applied to estimate the predictive power of several sets of prognostic factors for gastric cancer in Japan using data from a large clinical trial.     

Fecal stream is essential for adaptive induction of glucose-coupled sodium transport in the remnant ileum after total proctocolectomy

Our previous studies demonstrated that sodium glucose cotransporter 1 (SGLT-1) was induced in the remnant ileum of total colectomized rats via the action of factors other than hyperaldosteronism. The aim of the present study was to clarify whether fecal stream is required for the enhancement of SGLT-1-mediated sodium transport. Twenty-seven pairs of ileal tissues were obtained from the proximal and distal side, respectively, of loop ileostomy after total proctocolectomy. Mucosae were mounted in an Ussing chamber to evaluate glucose-coupled sodium transport. Levels of SGLT-1 mRNA in proximal and distal mucosae were compared by Northern blotting. Villous height and crypt depth were measured to test for correlations between mucosal structure and SGLT-1-mediated sodium transport or mRNA expression levels. Both glucose-coupled sodium transport and expression of SGLT-1 mRNA were significantly lower in distal mucosae relative to proximal mucosae. In distal mucosae, villous height, but not crypt depth, was significantly lower than in proximal mucosae, demonstrating a positive correlation between villous height and SGLT-1 function and expression. Comparative studies of proximal and distal mucosae demonstrated that in addition to hormonal changes, fecal stream is required for full induction of the sodium transport system (which includes SGLT-1-mediated transport) in the remnant ileum following total proctocolectomy. Presented in part at the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 14–19, 2005 (poster presentation). This work was supported by Grants-in-Aid for Scientific Research 10557118 and 14657295 from the Ministry of Education, Science and Culture of Japan to K. Fukushima, and by Kanae Foundation to K. Fukushima.     

Remote Connection to the Kyushu University Medical Center LAN Using Digital and Analog Telephone Lines

SOHO (Small Office/Home Office) has recently become popular, as it makes working at home possible. Computers or Local Area Networks(LAN) connected to the office network from home are necessary for the implementation of this concept. Kyushu University has begun a service connecting home computers to the campus LAN for researchers, staff and students of the Faculty of Medicine. We have two different telephone connection methods. One connects the campus LAN and the home computer LAN using routers through the Integrated Services Digital Network (ISDN). The other connects computers at home to the workstation in the university, using modems and the PPP (Point to Point Protocol) through a public telephone analog line. This paper outlines our university SOHO connection system and discusses the merits and demerits of using telephone line connections.     

Acetylcholine suppresses the spread of excitation in the visual cortex revealed by optical recording: possible differential effect depending on the source of input

Optical recording with a voltage-sensitive dye was performed in visual cortical slices of the rat to determine the effect of acetylcholine (ACh) on the spread of excitation. In the presence of ACh, the spread of excitation initiated by stimulation at the white matter/layer VI (WM/VI) was greatly suppressed throughout the cortex, with less suppression in the middle layers. By comparing the effect of ACh with that of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the fraction of the synaptic component that was sensitive to ACh was evaluated. ACh suppressed approximately 40-50% (maximum 55.8%, n = 11) of the initial synaptic component in the superficial and deep layers. In the middle, however, the effect was weakest and only approximately 20-30% (minimum 20.9%, n = 11) of the initial synaptic component was suppressed. On the basis of histological analysis, the region with the weakest ACh effect extended from upper V to lower II/III. To identify the site of ACh action in terms of pre- versus postsynaptic localization, exogenous glutamate was applied. Because ACh did not suppress the excitation induced by glutamate, the site of the ACh action was indicated to be presynaptic. When layer II/III was stimulated instead of WM/VI, the suppression was uniform throughout the cortex. A muscarinic receptor antagonist, atropine, blocked the suppression by ACh. In conclusion, our results indicate the following two points. First, ACh strongly suppresses intracortical connectivity through presynaptic muscarinic receptors. Secondly, in contrast to the intracortical connection, some group(s) of fibres, possibly thalamocortical afferents that arise from white matter and terminate in the middle cortical layers are suppressed much less by ACh. While ACh has been reported to have confusingly diverse effects, e.g. direct depolarization and hyperpolarization as well as synaptic facilitation and suppression, its effect on the propagation of excitation is very clear; suppression on intracortical connection, leaving thalamocortical inputs rather intact. We postulate that cholinergic innervation enables the afferent input to have a relatively dominant effect in the cortex.     

Micro-mainframe-link Personal Clinical Research System

We constructed a micro-mainframe-link clinical research system for personal use (Personal Clinical Research System). This system was developed with both a mainframe computer and a personal computer (PC). The prepared programs included a database manager (on the mainframe computer), a user interface program (on the PC), and a communication control program that connected the mainframe computer with the PC. The database on the mainframe computer was constructed by two methods. The first method was to transmit data from the PC to the mainframe computer. The second method was to extract data from the patient information database. Using this system, a physician is able to construct a personal research database that contains interesting data for the physician. In addition, the physician is able to accumulate data on a special field using this system. A discharge summary system is now in operation as an example of this system.     

Endoscopic mucosal resection of a rectal malakoplakia in a healthy adult

Malakoplakia in the gastrointestinal tract is rare in healthy young people without underlying disease. Sufficient tissue is required for accurate diagnosis. We describe a malakoplakia that developed in a healthy young woman and was treated by endoscopic mucosal resection (EMR). A 40‐year‐old woman with a history of taking oral contraceptives until one year earlier was referred to our hospital with anal bleeding and constipation. A colonoscopy carried out at our another hospital 18 months earlier disclosed no abnormal findings. Colonoscopy at presentation revealed a yellowish‐white tumor, 5 mm in diameter, in the rectum. The lesion was slightly protruded and had a smooth flat surface, without erosion or ulceration. EMR was carried out for a definitive diagnosis. Histopathological examination showed that the tumor contained granular histiocytes, positive for CD68 and negative forcytokeratin (AE1/AE3). Several histiocytes contained intracytoplasmic round bodies (Michaelis–Gutmann bodies), which reacted positively with periodic acid‐Schiff and calcium (Von Kossa) stains. Intracytoplasmic Escherichia coli (von Hansemann bodies) were identified by Giemsa staining. Based on these results, the tumor in the rectum was diagnosed as a malakoplakia. Following EMR, the patient did not receive further treatment for malakoplakia because she had no symptoms associated with malakoplakia. She has been well for more than 9 months, with no symptoms of disease. Awareness of colorectal malakoplakia is important in patients taking steroids, including oral contraceptives.