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This paper reviews the problems and methods in the treatment of patients suffering from short bowel syndrome (SBS) after removal of large parts of the small intestine. Twenty-eight patients with severe SBS received medical treatment at our department from 1966 through 1989. All patients who could pass through the first postoperative period with the help of intravenous hyperalimentation (IVH) received further IVH or enteral hyperalimentation at home to maintain nutritional condition and promote social rehabilitation. Six patients unable to receive hyperalimentation died from insufficient nutrition within 2 years after the intestinal resection. Seventeen (77%) of the 22 patients who received parenteral or enteral hyperalimentation at home survived and rehabilitated socially. Of five patients (23%) whose remnant small intestines were shorter than 70 cm, four died of pneumonia caused by malnutrition in spite of receiving parenteral or enteral hyperalimentation. The other died of senility 13 years after the operation. The nutritional assessment indicated that the serum concentrations of albumin in those patients who died of malnutrition were significantly decreased compared with those of the survivers. Among many other nutritional parameters, only the percentage of AMC (arm muscle circumference) and serum concentrations of PA (prealbumin), RBP (retinol binding protein) and Zn showed statistically significant decreases from the normal range in the longer surviving patients. Among the causes of the nutritional deficiency of patients with SBS, statistically significant derangements of digestion and absorption of fat and protein were observed. In order to ensure hyperalimentation at home for SBS patients the following measures are essential: 1) Patients whose remnant small intestine is shorter than 30 cm will need home parenteral nutrition (HPN) throughout life. 2) Although 2/3 of patients whose remnant small intestine is 30-70 cm in length gradually become able to tolerate

This paper reviews the problems and methods in the treatment of patients suffering from short bowel syndrome (SBS) after removal of large parts of the small intestine. Twenty-eight patients with severe SBS received medical treatment at our department from 1966 through 1989. All patients who could pass through the first postoperative period with the help of intravenous hyperalimentation (IVH) received further IVH or enteral hyperalimentation at home to maintain nutritional condition and promote social rehabilitation. Six patients unable to receive hyperalimentation died from insufficient nutrition within 2 years after the intestinal resection. Seventeen (77%) of the 22 patients who received parenteral or enteral hyperalimentation at home survived and rehabilitated socially. Of five patients (23%) whose remnant small intestines were shorter than 70 cm, four died of pneumonia caused by malnutrition in spite of receiving parenteral or enteral hyperalimentation. The other died of senility 13 years after the operation. The nutritional assessment indicated that the serum concentrations of albumin in those patients who died of malnutrition were significantly decreased compared with those of the survivers. Among many other nutritional parameters, only the percentage of AMC (arm muscle circumference) and serum concentrations of PA (prealbumin), RBP (retinol binding protein) and Zn showed statistically significant decreases from the normal range in the longer surviving patients. Among the causes of the nutritional deficiency of patients with SBS, statistically significant derangements of digestion and absorption of fat and protein were observed. In order to ensure hyperalimentation at home for SBS patients the following measures are essential: 1) Patients whose remnant small intestine is shorter than 30 cm will need home parenteral nutrition (HPN) throughout life. 2) Although 2/3 of patients whose remnant small intestine is 30-70 cm in length gradually become able to tolerate

Restorative proctocolectomy with ileal reservoir has become an accepted form of treatment for ulcerative colitis and familial adenomatous polyposis. Five types of reservoirs have been developed: the S pouch, J pouch, H pouch, W pouch and K pouch. This paper reviews the differences in the clinical and functional outcomes among the various reservoir designs and their sizes. From the results of the reported series, the best clinical function is apparently that associated with a large volume and highly compliant pouch which empties spontaneously. The S pouch has a high rate (35-53%) of catheterization for evacuation. On the other hand, the W and K pouches have larger and wider reservoirs with a higher compliance than of the J pouch. However, since cases in which the K pouch as well as H pouch have been used are few, a larger number of patients will be necessary to reach a conclusion regarding the best treatment. The present conclusion is that the W pouch has the best functional outcome concerning defecation.

The effects of eight weeks of endurance training on autonomic nerve function was assessed by measuring spectral changes in heart rate variability and blood cell counts in 12 healthy subjects. After the 8 week training program, heart rates significantly decreased after training at pre-load resting, during loading, and post-load resting. Low frequency component (LF) power slightly increased from the pre-load resting to the loading phase before the training, but slightly decreased from the pre-load resting to the loading phase after the training. These were not significant, but the difference between the slight increase and the slight decrease was significant (p<0.05). The other parameters including high frequency vagal component (HF) power and LF/HF were not significantly changed from the pre-load resting to the loading phase both before and after the training. These results show that sympathetic nerve activity from pre-load resting to loading decreased after training, while parasympathetic nerve activity was not changed. Mean corpuscular volume increased significantly, while lymphocyte count (LYP) decreased significantly (p <0.05) from before to after training (p<0.05), respectively. Changes in LF power at pre-load resting were positively correlated with changes in LYP from before to after training (p<0.05). Changes in HF power at pre-load resting were negatively correlated with changes in LYP from before to after training (p<0.05). In conclusion, eight weeks of endurance training caused an adaptation in the sympathetic nerve function, but not in the parasympathetic nerve function.

This study was done to determine the correlates of restenosis after deployment of the PalmazSchatz stent. Clinical, procedural and quantitative angiographic data from 85 consecutive patients (92 lesions) with successful stent deployment (diameter stenosis <50%) were analyzed. All patients had follow-up angiography 6.5±2.5 months after stenting. Minimal luminal diameters and diameter stenosis before and immediately after the procedure were 0.82±0.35 mm, 67.8±11.5% and 2.96±2.16mm, 0.9±19.3%. The number of deployed stents was 1.1 ±0.4. At follow-up, minimal luminal diameter was 1.93±0.75 mm and diameter stenosis was 23.4±27.6%. Restenosis (diameter stenosis≧50%)occurred in 16 (17.4%) lesions. The incidence of diabetes was significantly higher in the restenosis group than non-restenosis group (62.5% vs. 19.7%; p=0.0005), and lesion length was longer (16.2± 9.2 mm vs. 10.0±6.2 mm; p=0.0077). Other variables did not show differences between the two groups. Using logistic regression analysis, a multivariate study showed that restenosis was correlated only with diabetes (p < 0.0001, RR=18.18, 95%CI=3.38-97.68). In diabetic patients, HbAlc was higher in the restenosis group than the non-restenosis group at the time of stent deployment (7.6±0.7% vs. 6.3±1.4%; p=0.0484). Conclusion: Restenosis after the Palmaz-Schatz stent is strongly concerned with diabetes mellitus.

We report an interesting case with a primary ulcerating tumor of the ampulla of Vater associated with multiple primary pancreatic ductal microadenocarcinomas. All of these pancreatic microcarcinomas (number, 69; size, 0.04-1.25mm) were histologically proved to be primary and independent of each other, and were distributed throughout the head, body, and tail of the pancreas. They were all located in the small interlobular ducts and the ductules (including intercalated ducts and centroacinar cells). Sixty-three of 69 microcarcinomas were in-situ carcinomas, and the remaining 6 were microinvasive. All microcarcinomas were well-differentiated tubular adenocarcinomas with ordinary cell phenotypes, high-grade cytologic atypia, and adjacent only to normal ordinary pancreatic ductal cells, but not to mucous cell hyperplasia. Immunohistochemically, all of the microcarcinomas showed p53-protein overexpression (p53 positive index: 91.6 ± 8.10% in 12 tumors tested), high proliferative activity (Ki-67 positive index: 64.9 ± 13.3% in the same 12 tumors), and no Ki-ras mutation detected by nested PCR-RFLP in the 12 carcinomas. We concluded that pancreatic microcarcinoma in this case arose from ordinary pancreatic ductal cells of the small ducts and ductules by way of p53 alteration without Ki-ras mutation, and that histogenesis was different from that of the more common Ki-ras-mutated carcinoma arising from metaplastic mucous cells of mucous cell hyperplasia.

Two patients with postoperative traumatic chylothorax following thoracic esophagectomy for esophageal carcinoma are presented. Both cases of chylothorax were cured by transhiatal supradiaphragmatic ligation of the thoracic duct, our original expedient for supradiaphragmatic ligation of the thoracic duct without thoracotomy. This procedure is simple and easy to perform, and should be feasible for any type of traumatic chylothorax because of the anatomical pathway of the thoracic duct. It also should be preferable for patients with severe intrathoracic adhesions or those with cardiopulmonary complications. We expect that the transhiatal technique for supradiaphragmatic ligation of the thoracic duct will have comprehensive feasibility as a surgical modality for traumatic chylothorax, and might well be an alternative to the transthoracic procedures currently advocated.

In the present study the frequency of hemoglobin'S' was determined based on 10 tribal families and 31 non-tribal families of Andhra Pradesh, South India. The incidence of sickle cell anemia was found to be high in males as compared to females in both populations. Sickle cell trait remained more or less equal in both sexes. The gene frequency (q) of HbS was also predominantly high in males (0.231, 0.387 and 0.347) as compared with females (0.072, 0.297 and 0.241) in native, nonnative, and pooled sample' respectively. Sex ratio in HbSS individuals in both groups was found to be 2: 1, which showed a statistical significance, whereas no such deviation was observed in heterozygotes (SS). There was no significant relationship between parental genotypes or sex ratio among offspring. It is known that in acute anemic conditions, the chain synthesis is switched on to combat anoxic conditions due to a lowered hemoglobin level. We have estimated HbF levels in different genotypes, i. e. AA, AS & SS. The mean HhF levels were significantly elevated in SS genotype. This indicates that the γ chain synthesis is an alternative in acute hemolytic episodes due to the sickling.

Two fatty acid binding proteins, liver and intestinal, have been identified in the rat intestine. Both are thought to be closely related to the absorption and metabolism of fatty acids in the intestinal epithelium. However, the underlying mechanism is not clearly understood. The purpose of this study was therefore to investigate the roles of these two fatty acid binding proteins in the intestinal absorption of fatty acids. Rats were fed diets varying in fat content for two or four weeks. Liver and intestinal fatty acid binding proteins were extracted from the duodenum, jejunum and ileum, and their concentrations were measured using the single radial immunodiffusion method. Rats fed with a high fat diet for two weeks had a significantly increased liver fatty acid binding protein concentration in the jejunum, and a significantly increased intestinal fatty acid binding protein concentration in both the jejunum and the ileum in comparison with the duodenum. Rats fed a high fat diet for four weeks also had a significantly increased liver fatty acid binding protein concentration in the jejunum, and a significantly increased intestinal fatty acid binding protein concentration in the ileum compared with that in the duodenum. Since the increase in the concentrations of liver and intestinal fatty acid binding proteins varied depending on the amount of fat, we speculate that liver and intestinal fatty acid binding proteins possess different mechanisms in the absorption and metabolism of fatty acids.

We previously demonstrated that tumorspecific effector cells could be generated from tumordraining lymph node cells by in vitro sequential activation with anti-CD3 mAb and IL-2. In the present study, we further examined cellular interactions and mechanisms of the antitumor effect. Tumor-draining lymph node cells (TDLN) of a weakly immunogenic fibrosarcoma, MCA 205, were activated by the anti-CD3/IL-2 method and transferred into the peritoneal cavities of mice bearing 5-day established peritoneal dissemination of MCA 205 tumor cells. Intraperitoneal injection of anti-CD3/IL-2-activated TDLN significantly prolonged the survival period, and 80% of treated mice remained tumor free for more than 80 days. In vivo depletion of host macrophages with GdCI_3 clearly abrogated the antitumor effect, while the elimination of host T cells with sublethal irradiation (500 R) did not, indicating that host macrophages are indispensable in the antitumor effect. In vitro cytotoxicity and cell proliferation were further examined in detail to determine the commitment of macrophages and mediator cytokines. Although anti-CD3/IL-2 activated cells mediated minimal cytotoxicity in a 4-hr ^<51>Cr releasing assay, tumor specific cytolytic action was detected in an 18-hr assay with coexisting peritoneal cells. The results suggest that peritoneal macrophages play an indispensable role in this treatment effect and that T cell-macrophage interactions were mediated by IFN-γ, the importance of which was exhibited in the early phase of the tumor-effector-macrophage contact.

Localization of thymosin β4(Tβ4) in human and rat skin was examined by immunohistochemistry using a monoclonal antibody against Tβ4. The specificity of the monoclonal antibody to Tβ4 was verified by Western blot analysis, where the antibody reacted to recombinant Tβ4 but not to thymosin β10(Tβ10), and stained a band corresponding to Tβ4 in the homogenate of human skin. By double immunostaining for Tβ4 and S-100 protein or by immunohistochemical staining for Tβ4 and CD1a or HLA-DR on sequential sections, the Tβ4^+ cells were identified in the epidermis as cells which also expressed S-100 protein, CD1a or HLA-DR. The findings indicate that Tβ4^+ cells in the epidermis are Langerhans cells (LC), and propose Tβ4 to be a marker of LC in the epidermis. Actinfilaments in the LC may be implicated in the migration of their progenitors from the circulation to the epidermis and in their intimate adhesion to keratinocytes. Tβ4 may play an important role in the polymerization and depolymerization of actin during these processes.

The products of homeobox genes are DNAbinding transcription factors. However, little is known about downstream genes whose activities are regulated directly or indirectly by the homeobox genes. In the current study, we tested a differential display (DD) method using the tissue of a knockout mouse in order to identify the downstream genes of a homeobox gene Msx1 systematically. Our previous in situ hybridization analysis of a Msx1 deficient mouse showed that Msx1 induced by epithelial bone morphogenetic protein 4 (BMP4) and fibroblast growth factors (FGFs) induces Bmp4, the HMG box gene Lef1, and the heparan sulfate proteoglycan syndecan-1 in the tooth mesenchyme. Although it is a very powerful approach for identifying downstream genes of a homeobox gene to test whether the candidate gene's expression is affected in the knockout mouse, this approach is not directly applicable to the identification of unknown genes downstream of Msx1. In the current study, we performed DD using total RNA from E14.5 Msx1 mutant mandibles and were able to obtain four novel downstream genes of Msx1 from 20 cDNA clones verified by Northern blot hybridization and semiquantitative RT-PCR. Despite several problems inherent to this method, we concluded that DD analysis using the tissue of a knockout mouse is a useful systematic approach for the identification of downstream genes of a homeobox gene.

Background/Aims: We investigated intrahepatic leukocytes in the regenerating rat liver following 70% partial hepatectomy, using anti-CD4 and CD8 antibodies on a FACScan. Materials and Methods: Rat leukocytes were divided into two groups by CD4 single staining, CD4^ and CD4^.CD4b^ cells were mainly CD3^+T lymphocytes, while CD4^ cells were mainly macrophages in the blood or normal spleen as previously reported. Results: We found CD4^CD3^- cells specifically in the liver in normal rats by two-color flow cytometry. This cell type was not present in the blood or spleen in normal rats. However, their numbers decreased in the liver and increased in the spleen following 70% partial hepatectomy. CD8^+T cells displayed a lower expression of CD3 molecules than did CD4^+T cells. Conclusions: CD4^CD3^- cells were demonstrated mainly in the liver. Their numbers were affected by the 70% partial hepatectomy. They therefore may play a role in liver regeneration after partial hepatectomy.

The possible mechanisms leading to acute cardiopulmonary arrest (CPA) soon after a subarachnoid hemorrhage (SAH) are still controversial. Cardiac arrest, which has been thought to be mainly related with arrhythmia triggered by the onset of SAH, is less common than respiratory arrest without circulatory collapse but is not a negligible cause of sudden death after SAH. A 69-year-old man with angina pectoris suffered cardiac arrest immediately after the loss of consciousness during coronary angiography. His angiogram revealed a vasospasm of the left coronary arteries which had induced the cardiac arrest. The cause of loss of consciousness was diagnosed as a SAH by brain computed tomography (CT). It is strongly suggested that the onset of the SAH triggered the coronary vasospasm which in turn induced cardiac arrest. Our case clarified that sudden death soon after SAH may be partly caused by cardiac arrest induced by coronary vasospasm. This case report may resolve some aspects of the controversy over the cause of primary cardiac arrest following SAH.

Carbon monoxide (CO) is a candidate for neural messengers involved in synaptic plasticity. Heme oxygenase (HO), which produces carbon monoxide (CO) by oxygenation of heme, is present in neocortical pyramidal cells. In this study, we investigated the role of CO in neocortical long-term potentiation (LTP) using slices prepared from the rat auditory cortex. Tetanic stimulation of layer IV pruduced LTP of field potentials in layer II/III (LTP_II/III ) and in layer V (LTP_v ). CO (8 nM-5 ,uM) showed no significant effect on LTP_II/III , while CO significantly suppressed LTP_v at concentrations of 40 nM and 200 nM. N^G-nitro-Larginine(NA, 10 ,uM), a NO synthase inhibitor, blocked LTP_v • This blockade of LTP_v by 10,uM NA was reversed by 8-bromo-cGMP (Br-cGMP, 1 mM), a membranepermeable cyclic GMP analog. CO (40 nM) did not suppress LTP_v in the presence of 10,uM NA and 1 mM Br-cGMP. o-Aminolevulinic acid(ALA, 30,uM), which is a substrate for heme synthesis and is believed to facilitate endogenous CO production, significantly suppressed LTP_v • ALA showed no effect on LTP_II/III • These results strongly suggest that LTP_v but not LTP_II/III is suppressed by exogenous and endogenous CO probably via suppression of NO-induced cGMP formation.

Fiber type distributions of the fast-twitch extensor digitorum longus muscle in rats were examined after exposure to hypobaric-hypoxia for 5 weeks from the postnatal age of 5 weeks or for 10 weeks from the postnatal age of 10 weeks. Muscle fibers were classified into fast-twitch oxidative glycolytic (FOG), fast-twitch glycolytic (FG), or slow-twitch oxidative (SO). The percentage of FOG fibers was increased and that of FG fibers was decreased in the hypoxic rats at 10 weeks of age, while there was no difference in the percentage of SO fibers between the normoxic and hypoxic rats. There was no difference in the fiber type distribution between the normoxic and hypoxic rats at 20 weeks of age. These results indicate an age-specific response of hypobarichypoxia on the fiber types of the rat extensor digitorum longus muscle.

The effect of noradrenaline (NA), acetylcholine (ACh) and 5-hydroxytryptamine (5-HT) on the contractility of the vas-deferens smooth muscle isolated from rats treated with heat-killed E. coli (endotoxin) was investigated. The contractile tension to these drugs was significantly decreased as compared with control values at different post-treatment time periods except for 5-HT at 48 h post treatment time. The 48 h tissues showed an increased sensitivity to 5-HT, while the same doses produced a decreased contractility in the 72 h tissues. The structural integrity of the vas deferens is vital in the ionic transport mechanism essential to ExcetationContraction coupling. E. coli induced a decreased responsiveness of the vas deferens to these mediators probably due to the liberation of free radicals. The latter itself could cause damage to the oxidizable muscle membrane structures or by a direct action on the membrane enzyme systems. Either of these postulates will interfere with smooth muscle contractility and thus impede the passage of spermatozoa to the testes in the septic state.

A woman (gravida-2 para-0) with a history of two intrauterine fetal deaths accompanied with severe preeclampsia, who was positive for anticardiolipin- beta2 glycoprotein I antibody, was treated using prednisone and low-dose aspirin during a third pregnancy. This pregnancy continued uneventfully, and the prophylactic therapy was considered to be efficacious.

To determine the computed tomography (CT) and magnetic resonance (MR) characteristics of pineal region germinomas, the author reviewed images from 40 patients with pineal region tumors. These tumors were divided into two groups: those with germinomas (n =17), and those with other tumors in the pineal region (5 with a germ cell tumor other than germinoma; 8, mixed germ cell tumor; 8, pineal parenchymal tumor; and 2, miscellaneous tumors; n = 23). All cases were investigated with CT; 31 of the cases were also investigated with MR imaging. The following parameters comprised statistically significant differences between the two groups: maximum size of the tumor, tumor density of the precontrast CT, signal intensity of precontrast T1-weighted spin-echo images, and homogeneity of the tumor on both precontrast and postcontrast studies. This study found that extension patterns of pineal region tumors into the thalamus have significant implications in differentiating germinomas from other tumors of this region. Germinomas are characterized by thalamic extension without lateral displacement of the third ventricle walls due to direct compression by tumors (P =.0034). The analysis of tumor extension patterns, combined with the parameters mentioned above, may provide a more accurate differential diagnosis in pineal region tumors, leading to prompt and appropriate treatment.

We have previously demonstrated that pulsed electromagnetic fields (PEMF) affect the functional differentiation of rabbit growth plate chondrocytes in culture by enhancing the response of the parathyroid hormone (PTH). In this study, we examined whether the PEMF affect the proliferation of cultured chondrocytes as well as how their effect on the PTH response of the chondrocytes is related to the calcium metabolism. We cultured growth plate chondrocytes isolated from the ribs of young rabbits and treated them with Verapamil, a calcium blocker, under exposure to PEMF (pulsating recurrent burst, an average of 2 gauss). No significant effect on [3H] -thymidine incorporation into DNA synthesis in either the confluent or logarithmic phase was observed under exposure to PEMF. Verapamil: 1) inhibited DNA synthesis dose-dependently, whereas it did not change the level of glycosaminoglycan (GAG) synthesis; and 2) did not alter the level of PTH-dependent GAG synthesis in the presence or absence of PEMF. These findings indicated that PEMF stimuli resulted in the functional differentiation of growth plate chondrocytes by enhancing GAG synthesis in response to PTH, and that this effect was not affected by the change in the concentration of calcium ions.

To determine the efficacy of endoscopic retrograde cholangiopancreatography (ERCP) in detecting retained stones or bile duct injury immediately after following laparoscopic cholecystectomy (LC), 113 patients were reviewed undergoing LC between September 1993 and September 1996. Among them, 44 patients (38.9%) underwent ERCP within postoperative day 4. ERCP was indicated as follows: 1) patients with postoperative cholestasis and/or excessive amounts of bilious drainage from the intraabdominal drain; 2) patients with discrepancies between preoperative imaging modalities and intraoperative findings; and 3) patients without either preoperative ERCP or intraoperative cholangiography (IOC). Postoperative complications detected by ERCP included bile duct injury in 2 patients, retained common bile duct (CBD) stone in 1 patient, and hepatolithiasis in 1 patient. One patient mistakenly clipped CBD not to a cystic duct, and subsequent ERCP showed interruption of the bile duct so that an emergency operation was performed. Another patient had leakage from a cystic duct-CBD junction, and subsequent ERCP showed abundant leakage of the bile duct, so that endoscopic nasobiliary drainage (ENBD) was performed. The retained CBD stone was removed by endoscopic sphincterotomy (EST) following ERCP. In conclusion, ERCP immediately following LC in the selected patients on the basis of the above indications of 1) and 2) may be recommended as one useful method which detects accurately retained stones and bile duct injury.

This study measured luminol-enhanced chemiluminescence in patients with portal hypertensive gastropathy and investigated whether superficial reddening, a gastric mucosal change observed in patients with portal hypertension, should be included in the category of endoscopic findings of patients with portal hypertensive gastropathy. The subjects consisted of 36 histologically confirmed cirrhotic patients with a snake skin appearance or discrete red spots on the gastric mucosa (Group 1), 42 patients with superficial reddening on the gastric mucosa who had no liver disease (Group 2) and 32 controls. Luminol-enhanced chemiluminescence study of the gastric mucosal biopsy specimens showed that a significantly larger amount of chemiluminescence was produced in Group 1 than in either Group 2 or the controls, and that there was no significant difference between Group 2 and the controls. In histological examination, no significant differences were observed among the three groups in the extent of mucosal infiltration of small round cells and neutrophils. The mean ratio of the total vascular area to total mucosal stromal area was significantly higher in Group 1 and 2 than in the controls. Moreover, the ratio in Group 1 was statistically higher than that in Group 2. In a gastric mucosal hemodynamic study, Group 1 had a higher mean value of the index of mucosal blood volume (IHB ratio) and a lower mean value of the index of mucosal oxygen saturation (ISO_2 ) than Group 2 or the controls, which suggested congestion. In Group 2, ISO_2 was significantly lower than in the control group, but the IHB ratio was not different from the controls, which suggested that the superficial reddening reflected the increased consumption of oxygen in the mucosa but was not associated with congestion. From these findings, it is suggested that the differences in luminolenhanced chemiluminescence are related to the presence and absence of congestion. In view of the fact that congestion plays an important

Background: Insulin-like growth factor-I (IGF-I) is a polypeptide hormone that is an important mediator of cellular growth, replication, and differentiation. IGF-I provides a major stimulus for enterocyte proliferation and the absorptive function. The aim of this study was to determine the effect of the intraluminal administration of IGF-I on the gastrointestinal tracts of rats with methotrexate (MTX)-induced enterocolitis. Study design: Male Sprague-Dawley rats weighing 140 to 205 g were intraperitoneally implanted with osmotic minipumps that delivered either 0.9% NaCl (saline group; n=8) or 10 nM IGF-I (IGF group; n= 9) to the ileal lumen through a short silastic catheter at a rate of 1μL/h. Rats received 20 mg/kg intraperitoneal MTX at the time of catheter insertion. Forty-eight hours after the MTX infusion, the small intestine was excised to measure mucosal protein and DNA content in jejunal and ileal segments. Additional measurements during the study period included changes in body weight and urinary nitrogen loss. Results: No significant difference in plasma IGF-I levels was seen between the groups. The saline group lost more body weight than the IGF group (p<0.05). In the IGF group, neither protein nor DNA content of the jejunum differed from those measured in the ileum. However, the ratio of the ileal to the jejunal protein content was significantly higher in the IGF group than in the saline group. Conclusion: Intraluminal administration of IGF-I may play a role in changing the distribution of gut mucosal proteins, in this rat model of MTX-induced enterocolitis.

We investigated the presence of autoreactive T and B cells, extrathymic T cells (intermediate TcR cells), natural killer (NK) marker-positive T cells, and CD5^+B cells in the liver of older rats. Results showed that lymphocyte function-associated antigen-1 (LFA-1)^<+++>CD3^+ cells, which have a phenotype similar to that of intermediate TcR cells of mice, increased in the liver, spleen, and peripheral blood of older rats (55 weeks and 64 weeks of age) compared with young, normal rats. Conversely, LFA-1^<++>CD3^+ cells decreased in older rats. The LFA-1^<+++>CD3^+ cells displayed an intermediate staining intensity for CD3 compared with that of LFA-1^<++>CD3^+ cells and they seemed similar to extrathymic T cells in mice. However, the LFA-1^<+++> CD3^+ cells were almost all CD8^+, in contrast to those of mice. Double negative (DN) CD^<4->CD^<8->T cells comprised less than 1% of the T-cell population in rats. NK3.2.3^<++> T cells also increased in the liver, but not in the peripheral blood of older rats; conversely, NK cells decreased in older rats. CD5^+ B cells increased in the liver but not in the spleen and peripheral blood of older rats. Furthermore, class II positive T cells and interleukin-2 receptor (IL-2R) positive T cells increased in the liver of older rats. These results suggest that T cells with a phenotype similar to the extrathymic T cells of mice are present in the rat liver.

Portal venous blood flow (PVF) and systemic arterial pressure (SAP) were examined after dopamine (DA) injection into the portal or femoral vein in 66 percent hepatectomized rats. The portal injection of DA at 25 μg/kg/min evoked an increase in PVF without any change in SAP. PVF response due to portal DA injection tended to be dose dependent, and when portal venous resistance was defined as portal venous pressure/PVF, the resistance was reduced concomitant with an increase in PVF. The same dosage of DA injected into the femoral vein increased PVF with an increase in SAP. These results suggest that DA directly contributes to the PVF control under a hepatectomized condition, and that DA receptor in the portal vasculature is involved in this response.

To determine whether the administration of an angiotensin-converting enzyme inhibitor (ACEI) affects the renal hemodynamic changes and the renal handling of urinary protein excretion in response to a protein meal ingestion, we examined the changes in creatinine clearance (CCr) and urinary albumin excretion rate (AER) in response to the ingestion of a meal of tuna fish before and after the administration of enalapril 2.5 mg/day for one week in 7 healthy male volunteers. Before treatment with enalapril, CCr 0, 1, 2, and 3 (before and 1, 2, and 3 h after protein loading; mean±SD) were 118.8 ± 21.6, 136.8±21.7, 144.9^* ±23.2 and 135.9 ± 15.3 ml/min/1.73 m^2 (^*: p < 0.05 vs CCr 0), respectively. Corresponding values after treatment with enalapril were 124.9 ±21.4, 146.6^* ± 16.3, 139.3^* ± 16.9 and 136.0^* ±22.7 ml/min/1.73 m^2 (^*: p<0.05 vs CCr 0). Mean CCr 0, CCr 2 and individual maximal CCr after protein loading did not show any significant difference before and after enalapril administration (individual maximal CCr: before enalapril 150.3± 13.7 vs after enalapril 153.4±13.6 ml/min/1.73 m^2 , NS). Irrespective of the administration of enalapril, no significant differences were observed in AER values before and after the ingestion of the tuna fish meal. Thus, it might appear that in humans who have normal renal function and are receiving long-term treatment with ACEI, CCr 2 or individual maximal CCr after the ingestion of a tuna fish meal could be used as an index of "renal functional reserve". Furthermore, irrespective of the administration of enalapril, the ingestion of tuna fish meal did not affect the renal handling of urinary albumin excretion.

Homogenic T cells were injected into the renal subcapsule of 19 Lewis rats and the liver subcapsule of 8 Lewis rats to examine apoptotic changes induced by T cells. Resulting phenomena were compared with graft-versus-host reaction (GvHR) induced in 5 F_1 (DAxLewis) male rats by the injection of DA female lymphocytes. The positive cell numbers of interleukin II receptor (IL-2R), CD18 or CD5 antigen were counted on the peripheral and splenic lymphocytes. The proportions of peripheral IL-2R (αβ)-positive cells ranged from 3±2% to 12±5% in 23 of the 27 Lewis rats. Splenic IL-2R-positive cells ranged from 10% to 25% in all 27 rats. Based on the numbers of CD5-positive splenic lymphocytes, 20% to 100% of splenic T cells were judged to express IL-2R. In three of the remaining four rats, peripheral IL-2R (αβ)-positive cells ranged from 47% to 85%. One of the four remaining rats showed 94% expression of IL-2R (αβγ) on the peripheral lymphocytes: IL-2R (αβγ)-positive lymphocytes of the rat also expressed strongly CD18 and CD5 antigens. In the F_1 rats with early GvHR, IL-2R expression was observed on 13±2% of peripheral lymphocytes and 59±5% of splenic T lymphocytes, while IL-2R-positive cell % of control F_1 males were 15±7 and 55±9, respectively. Renal tubular disappearance due to apoptosis and glomerular accumulation were found in the renal cortex of the female rat with 94% IL-2R-positive cells. The same renal lesions were also observed in 6 other rats. Abundant Golgi's complexes were shown in a glomerular epithelial cell. In the T cell-inoculated liver, only focal lymphocyte proliferation was found abnormally around the sinusoid without the other apoptotic changes. IL-2R was strongly expressed on hepatocytes surrounding the focal lymphocyte proliferation. In the plasma of the F_1 rats with GvHR, secreted humoral factors which activated monocytes but not neutrophils were indicated by the phagocytic functions of apoptotic cells, in vitro. It was concluded that IL-2R on T ce

The effects of dietary fat and fiber on colonic carcinogenesis and tumor growth in rats were assessed. Over a period of 30 weeks, four groups of 10 animals were fed diets with: high fat and high fiber content; high fat content and no fiber; no fat and high fiber content; or no fat and no fiber. Five weeks after starting these diets, each group was divided into two subgroups, one receiving 10 weekly injections of the carcinogen 1, 2-dimethylhydrazine (DMH); (20 mg/kg/ week). The other (control) subgroups recieved no DMH. At 30 weeks the rats were killed and autopsies were performed. Results showed cancers were limited to rats receiving DMH. The average numbers of cancers per rat were 4.8±2.6 for the high fat and fiber group; 6.2± 4.6 for the high fat, no fiber group; 2.3± 1.5 for no fat, high fiber; and 2.2±0.8 for no fat, no fiber. High-fat animals tended to have more DMH-induced cancers than no-fat animals. Aggregate cancer volume per rat was smallest for the no-fat, high-fiber diet.

The preparation of biliary epithelial cells is fundamental for their biologic and pathophysiologic evaluation. A new method for the isolation of extrahepatic biliary epithelial cells, using explants of murine extrahepatic bile ducts and gallbladder, is presented. First, small tissue pieces of the extrahepatic biliary tree and the gallbladder were plated as primary explants on collagen gel. The epithelial cells spread from the explants toward the periphery as a monolayer sheet, while the nonepithelial mesenchymal cells of the explants migrated into the gel below the epithelial layer. These different growth patterns created areas in epithelial cell sheets in which no mesenchymal cells were present. These areas were cut with scissors and then cultured on another collagen gel as secondary explants. From these explants, epithelial cells without nonepithelial mesenchymal cells spread out as a monolayer on the collagen gel. At the front and periphery of both the primary and secondary monolayer cell cultures, epithelial cells exhibited a polygonal flattened morphology, and BrdUpositive S-phase cells were densely distributed. In the central parts of both explants, the cells were cuboidal or low columnar with a luminal mucin positive layer and BrdU-positive S-phase cells were sparsely distributed, suggesting that the in vivo morphologic characteristics of the epithelial cells of the extrahepatic biliary tree were retained. This method provides purification and a monolayer cell culture or extrahepatic biliary epithelial cells that can be employed in various types of studies.

To investigate the fetal development of the nail epithelium, the expression of hard keratin and epidermal keratin in human fetal skin at various stages of gestation was studied by immunofluorescence microscopy using anti-hair keratin and anti-epidermal keratin 10 monoclonal antibodies. Specimens were obtained from digits and scalps of fetuses at 11, 13, 16 and 20 weeks estimated gestational age. At 11, 13 and 16 weeks, hard keratin was coexpressed with epidermal keratin 10 in the nail epithelial field. At 20 weeks, the epidermal keratin 10 was no longer observed and only hard keratins were expressed in the nail matrix and bed, which were covered by an adult-like mature nail plate. In the hair apparatus and epidermis, such a coexpression of hard keratin and epidermal keratin 10 was not observed in any of the fetal stages examined. In conclusion, the coexpression of hard and epidermal keratins is one biological characteristic of the nail epithelium distinguishable from those of the epidermis and hair apparatus during human fetal development of keratinizing epithelia of the skin.

The effects of prostaglandin E_1 (PGE) on portal venous blood flow (PVF) and hepatic arterial blood flow (HAF) were examined in hepatectomized rats. The jugular injection of PGE produced a dose-dependent increase in PVF in 90 percent hepatectomized rats. The magnitude of flow responses obtained in order of the PVF per wet liver weight due to PGE fell into the following order: the 66 percent hepatectomized rats, the 90 percent hepatectomized rats, and lastly, the 40 percent hepatectomized rats. Intramuscular injection of indomethacin failed to affect PVF in the 66 percent hepatectomized animals. PGE had no effect on HAF in hepatectomized rats. These results suggest that the PGE action on PVF is amplified according to the volume of liver resected, but such PGE action is diminished when 90 percent of the liver is resected, and endogenous prostaglandins are inactive in the hepatectomized situation.

Twelve samples of α_1-anlitrypsin (AAT) were purified from six patients with hepatocellular carcinoma, one with pancreatic cancer and five healthy individuals, and subjected to the measurement of the fucosylated sugar chain. We compared different results from crossed immunoaffinoelectrophoresis (CIAE) with Lens culinaris agglutinin (LCA) and by the carbohydrate analysis of high-performance liquid chromatography (HPLC) with the pylidylaminated (PA・) oligosaccharides obtained from each AAT. A significantly good correlation was obtained between the percentage of PA-fucosylated biantennary sugar chains in whole PA-oligosaccharides of each AAT sample by HPLC analysis and the percentage of LCA-reactive species of AAT examined by CIAE. Thus, the percentages of LCA-reactive species of AAT examined by CIAE can be used as a substitute for the amount of fucosylated sugar chain of AAT.

In order to analyze the expression of cytokine receptors on a specified cell population, two-color flow cytometric analysis of cytokine receptors and surface markers using fluorescence labeled cytokines and monoclonal antibodies was performed. In normal peripheral blood cells, granulocytes expressed granulocyte colony-stimulating factor (G-CSF) receptor and interleukin-6 (lL-6) receptor, but mostly expressed interleukin-3 (lL-3) receptor weakly. Monocytes were positive for each receptor. In lymphocytes, CD3 positive T cells did not express any of these receptors; however, CD19 positive B cells expressed G-CSF receptor, IL-3 receptor, and partly expressed IL-6 receptor. In clinical cases, leukemic cells of acute myeloid leukemia (AML) patients tended to show the same characteristics as normal granulocytes and, in common acute lymphoblastic leukemia (ALL), B cell type chronic lymphocytic leukemia (CLL), leukemic cells tended to show the same characteristics as normal B cells. This shows that G-CSF receptors are expressed not only on myeloid cells but also on normal and leukemic B cells. Results show that two-color flow cytometry accompanied with surface marker analysis allows for the easy analysis of the expression of cytokine receptors on the specified cell population and the obtaining of useful information for clinical cytokine therapy.

From 1969 to 1995, 15 patients with Ebstein's anomaly underwent surgery at Niigata University Hospital. Two patients with an infantile form presented heart failure and cyanosis immediately after birth, and underwent a staged operation resulting in long-term survival in one of them (operative mortality 50%). For 13 patients with the adult form, 14 operations were performed on the tricuspid valve (10 valve replacements and 4 valvuloplasties) with 1 early death (operative mortality 7.7%). Five patients with bioprosthetic valve replacement had satisfactory results without any early or late deaths; however, 4 patients with mechanical ball or tilting disc valve replacement showed poor results with 1 early death, 1 reoperation, and 2 late deaths. Over the last four years, newly invented valvuloplasty techniques (Danielson's method and Carpentier's method) have been successfully performed on 4 patients, and we propose that the valvuloplasty should be considered in adult form cases whenever the anatomy is favorable.

The distribution of HLA Class I antigens was analyzed in 38 patients with reproductive autoimmune failure syndrome (RAFS), defined as patients who were positive for antiphospholipid antibodies and had experienced either recurrent fetal wastage and/or one or more experience of intrauterine fetal growth retardation with severe preeclampsia, and compared with the distribution in the general population in Niigata Prefecture, Japan. The distribution of HLA-A and -B antigens in patients with RAFS was not significantly different from that in the control group. The number of patients positive for HLA CW7 was significantly higher than that of the general population (132 normal healthy individuals) in this prefecture (Relative Risk; 3.47, 95% Confidence interval; 1.18-10.2). The compatibility of HLA antigens in spouses was also analyzed in 22 patient couples and 26 normal fertile couples, and there was no significant difference. Thus, it is suggested that HLA antigen systems might be involved in the genesis of reproductive autoimmune failure syndrome.

A 20-year-old man with two episodes of spontaneous hemorrhage occurring about 1 month before a hepatic artery aneurysm rupture is presented. The first hemorrhage appeared as intraperitoneal bleeding from a subserosal hematoma of the ascending colon, but soon after surgery the patient required transcatheter embolization for bleeding from a branch of the left iliac artery. The hepatic artery aneurysm was identified at emergency laparotomy a few weeks later. In retrospect, the earlier hemorrhages probably similarly represented small congenital visceral aneurysms. Multiple visceral aneurysms of a congenital nature involving different arteries are extremely rare. We here report a case with a unique combination of arterial sites.

Background: The systemic inflammatory response syndrome (SIRS) occurs after a wide variety of insults. Recent studies have revealed that the number of SIRS criteria exhibited by a patient may have clinical importance. For this reason, we sought to determine whether the magnitude of a surgical insult is associated with the number of SIRS criteria satisfied. Study design: We retrospectively investigated relationships between the number of SIRS criteria and the type of surgical procedure, either transthoracic (n = 79) or transhiatal esophagectomy (n =42), in 121 consecutive male patients younger than 75 years of age with carcinoma of the esophagus. Results: Operative injury was more extensive in the transthoracic group than in the transhiatal group in terms of the mean operative time (392 ± 65 versus 215 ± 70 min, p<0.0001) and estimated intraoperative blood loss (693±309 versus 436±316 mL, p<0.0001). Prevalence of SIRS did not differ between the two groups. Pyrexia was more frequent in the transthoracic group than in the transhiatal group (p =0.004). Conversely, tachypnea was commoner in the transhiatal than in the transthoracic group (p=0.0039). The mean number of SIRS criteria exhibited was the same, 2.1 ±0.9 in the transhiatal group and 2.3±0.7 in the transthoracic group. Conclusion: There was no difference in the mean number of SIRS criteria exhibited following either transthoracic or transhiatal esophagectomy for carcinoma of the esophagus, even though the magnitude of the operative injury was greater in patients undergoing transthoracic esophagectomy in terms of operative time and estimated blood loss. Our results show more a frequent occurrence of fever in the transthoracic group and a higher rate of tachypnea in the transhiatal group, a pattern possibly reflecting mechanical ventilation of the transthoracic patients.

The purpose of this study was to investigate the effects of various plant extracts of the genus used elsewhere on plasma glucose and serum insulin concentrations in normal and diabetic rats. Extracts of Solanum incarnum ripe fruit, Solanum incarnum roots, Opuntia megacantha leaves, Aloe chabaudii leaves, Morus alba leaves, Ficus thoningii bark, Allium sativum bulb and Tapinathus nyasicus leaves were given orally over a 5 week period at a dose of 20 mg/l00 g body weight to normal rats and rats made diabetic by streptozotocin (STZ). All the plants except S. incarnum roots and T. nyasicus leaves lowered plasma glucose concentrations. M. alba leaves, A. sativum bulb and F. thoningii bark had the greatest effect in both normal and diabetic rats, lowering glucose by between 17-31% in normal rats and 17-21% in diabetic rats in comparison with their respective controls. The plant extracts did not have any significant effects on plasma insulin levels in either normal or diabetic rats. The mechanisms for the hypoglycaemic effects observed are not clear but appear to involve mechanisms the are not insulinometric.

Retinol-binding protein (RBP) is the specific blood carrier protein for the transport of retinol (vitamin A). RBP is mainly synthesized in the liver, though several extrahepatic organs including the placenta may also synthesize RBP as high amounts of RBP mRNA have been detected in these. Here we purified human placenta RBP (pRBP) and examined its characteristics in comparison with human plasma RBP (sRBP). pRBP showed cross-immunoreactivity with sRBP, but the difference was noted in the molecular weight as determined by SDS-PAGE. Since the amino-terminal amino acid sequence of pRBP was identical with that of sRBP, the lower molecular weight of pRBP suggests that pRBP is the truncated form in which several carboxyl-terminal amino acid residues of sRBP have been removed. pRBP can also be distinguished from sRBP in the elution pattern on high performance liquid chromatography and in the time course of fluorescence quenching of retinol bound as ligands to RBPs. These data suggest that pRBP may playa specific role in the placenta in connection with reports that extrahepatic RBP may be involved in the retinol transport and recycling.

Background: Clinically, many attempts at small intestinal transplantation in humans have been performed. Although little is known about the long term results on motor function of the transplanted small intestine, small intestinal motility should continue to be one of the most important issues in small intestinal transplantation. Study design: We investigated small intestinal motility 10 to 15 months after orthotopic small intestinal transplantation in rats. Six male Lewis rats underwent orthotopic jejunoileal transplantation. Intestinal myoelectric activity was recorded in the rats using Ag-AgCl bipolar electrodes. Six age-matched Lewis rats were also studied as controls. Results: The cycle length of migrating myoelectric complexes (MMCs) in the transplanted jejunum (T-J), recipient's jejunum (R-J), and jejunum of the control rat (C-J) groups were 16.2±3.8 min, 13.7±1.4 min, and 1l.1±0.3 min, respectively. In the C-J and T-J, a respective 98.1% and 96.5% of phase IIIs at the distal site occurred following the phase IIIs at the proximal site within 20% variation of the MMC period. However, between the R-J and T-J, only 31.0% of phase IIIs occurred within 20% variation of the MMC period. Coordination of the MMCs between the recipient and transplanted intestine did not occur at 10 to 15 months after the operation in the rat. During fasting, MMCs were clearly identified in the small intestine of both control and transplanted rats. Feeding interrupted the periodic activity, and irregular spike activity was observed along the entire small intestine, though conversion of the fasting to the fed pattern was delayed by about a minute in the graft intestine. The slow wave frequencies in the T-J, R-J, and C-J were 32.8±2.7 cpm, 36.3 ± 2.7 cpm and 36.3 ± 2.4 cpm, respectively. Conclusion: These results suggest that the motility of the transplanted small intestine is mostly preserved, however, temporal coordination of the MMCs across the anastomosis did not occur after transplant

The sites of atrial fibrillation genesis and electrophysiological parameters of the atria were evaluated in 24 patients with Wolff-Parkinson-White (WPW) syndrome with induced atrial fibrillation in an electrophysiologic study. The twenty-four patients, 8 females and 16 males had a mean age of 42± 16 years. Atrial electrogram was recorded at three atrial sites during the initiation of atrial fibrillation: the high right atrium (HRA), the His bundle electrogram recording site (HBE), and the coronary sinus (CS). The site of atrial fibrillation genesis was determined as the recording site that first showed fragmented atrial electrogram at the time atrial fibrillation occurred. Atrial fibrillation was generated from the HRA site in 15/24 patients, the HBE site in 6/24 patients, and the CS site in 3 patients. Atrial effective refractory period (AERP), atrial wave duration at the HRA site (A1), prolongation of atrial wave during premature beat at the HRA site (%A2/A1), prolongation of atrial wave duration at the CS site during retrograde excitation of the atrium (% Cret/Cant), antegrade and retrograde effective refractory period of the accessory pathway (Kant-ERP, KretERP), and wavelength index (WLI) were evaluated in each patient. Only the %A2/A1 and WLI were significantly different among the groups with different sites of atrial fibrillation genesis. Atrial vulnerability of the HRA site was highest in patients with HRA genesis of atrial fibrillation as represented by the largest %A2/A1 and shortest WLI at the HRA recording site. Although different types of atrial fibrillation might occur, the HRA site is considered to play an important role in initiating atrial fibrillation in patients with WPW syndrome.

We investigated the relationship between the activation of phospholipase A_2 (PLA_2) and C (PLC) induced by thrombin in human platelets. Lysophosphatidylinositol (LPI) formation, an indicator of PLA_2 activation, was completely inhibited by pretreatment with pertussis toxin, but inositol-1, 4, 5-triphosphate (IP_3) formation, an indicator of PLC activation, was reduced by about 50%. Prostaglandin E_1 inhibited IP_3 formation completely, but only reduced LPI formation by about 50%. However, cholera toxin did not affect either formation. Conclusion: 1) The differential sensitivity of PLA_2 and PLC to pertussis toxin and PGE_1 strongly suggests that the activity of both enzymes is modulated by distinct GTP- binding proteins; 2) pertussis toxin sensitive G-protein is involved in the thrombin-induced platelet activation process, but cholera toxin is not.

Ultrasonography of a 65-year-old male experiencing pain in the epigastric region and fever revealed a thickened gallbladder wall with an oval, linear intraluminal structure. The patient was diagnosed as having acute cholecystitis with desquamated mucosa and was conservatively treated with antibiotics. Follow-up ultrasonography performed one week later revealed many mobile fragments with no acoustic shadowing in the gallbladder. Two weeks later, ultrasonography showed sludge in the gallbladder, which disappeared spontaneously 4 weeks later. After endoscopic retrograde cholangiopancreatography (ERCP) confirmed gallstones in the common bile duct, cholecystectomy with choledocholithotomy was performed two months later. In this report, the follow-up ultrasonograms, taken over a 4-week period, are presented in order to show the healing process of desquamated mucosa associated with acute cholecystitis.

A 53-year-old woman exhibited an endometrial squamous cell carcinoma (ESCC). There was a large mass in the corpus. The residual normal endometrial gland adjacent to ESCC showed no metaplasia. We may consider this case as carcinogenesis from pluripotential stem cells.

Background: Endocrine cell tumors of the gastrointestinal tract are divided into the carinoid tumor (CD), a low-grade malignancy, and endocrine cell carcinoma (ECC), a high-grade malignancy. In this study, nuclear morphometry and proliferating cell nuclear antigen (PCNA) immunohistochemistry were performed to distinguish objectively between CDs and metastasizing CDs or ECCs. Methods: Nuclear morphometry and PCNA immunohistochemistry were performed on the following colorectal endocrine cell tumors: 15 primary CDs and 1 metastatic focus, 5 primary ECCs and 3 metastatic foci, and their counterparts of 5 solid adenocarcinomas and 3 metastatic lesions. To differentiate the tumors from one another and to elucidate which features are responsible for metastasis in CDs. Results: Nuclear morphometric values (area, circumference, and short diameter) significantly increased in the order of CDs, ECCs, and adenocarcinomas, and were positively correlated with the PCNA index (PI) and particularly with a PI of strongly positive cells (PI-S). The PI and PI-S significantly increased in the order of CDs, ECCs, and adenocarcinomas (p <0.01). A 20.0 x 17.0 mm CD, which extended down into the muscle layer metastasized to the lymph nodes and liver, contained a high-grade atypical (HGA) area. The HGA area, 10.6 mm^2 located in the submucosa, showed nuclear morphometric values quite similar to those of a nodal metastatic lesion, and its PI and PI-S were significantly higher than in the remaining primary CD area, but lower than in ECCs. Conclusions: Nuclear morphometry and PCNA index are useful for distinguishing CDs from more malignant CDs or ECCs, and for detecting the progressive potentiality of CDs.

The effects of the oral administration of ginseng extract (GE, the root of panax ginseng C. A. Meyer) and its constituents (GRG, ginsenoside-Rg_1 and GRB, ginsenoside-Rbl_1) on liver regeneration were examined in 66% hepatectmized rats. When liver regeneration was evaluated by the mitotic index of the hepatocyte (MI), a significant increase in the MI was observed 2 and 3 days after GE administration, and the MI response was dose-dependent. Food intake was not affected by GE administration, nor there was any change in the serum insulin concentration. It was also noted that the oral administration of GRG produced a MI response similar to that caused by GE administration. Serum parameters indicating liver and kidney function were unchanged after GE administration. These observations lead us to conclude that orally administered GE and its specific constituent are capable of stimulating liver regeneration without serious systemic effects.

Serum thrombomodulin (sTM) concentration, a marker for the endothelium, is increased by endothelial damage or by decreased renal clearance. In this study, we followed up 65 diabetic patients for more than five years to assess the relationship between complications and sTM concentrations. At the beginning, 31 of 65 patients had a high sTM concentration (≧25.9 ng/ml). In this group (the HsTM Group), prevalences of diabetic retinopathy and nephropathy amounted to 14 cases (45%) with 9 cases (29%) at the beginning, and 17 cases (55%) and 7 cases (23%) at the end of follow-up period, respectively. On the other hand, in 34 patients with normal sTM concentrations (the NsTM Group), there were 11 cases (32%) and 4 cases (12%) at the beginning, and 14 cases (41%) and 6 cases (18%) at the end of the period, respectively. There was a negative correlation between sTM and TM clearance (CTM) both for those with and without diabetic nephropathy; the sTM levels with nephropathy were higher than those without nephropathy at the same CTM, suggesting more marked endothelial damage in the patients with nephropathy than those without nephropathy. Furthermore, 11 out of 24 patients in the HsTM Group were diagnosed to have ischemic heart diseases, and 3 patients later died of myocardial infarction. On the other hand, only four out of 31 patients in the NsTM Group had ischemic heart disease. In conclusion, sTM concentration seems to be a warning marker for developing diabetic complications, especially coronary heart disease. Increased endothelial damage seems to result in increased sTM levels even in the patients with diabetic nephropathy.

Mutation of the K-ras codon 12 was examined in 17 gallbladder carcinomas and 14 nonneoplastic gallbladder mucosa in patients with anomalous arrangement of the pancreaticobiliary duct (APBD), using nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. In addition, we investigated the relationship between the K-ras mutation and cellular proliferation using Ki-67 (MIB1) monoclonal antibody. Mutation of K-ras codon 12 was found in 7 of 17 (41.2%) gallbladder carcinomas but not in nonneoplastic gallbladder mucosa. There was neither a correlation between the presence of the K-ras mutation and the size or depth of invasion of the carcinoma, nor any statistically significant difference in cellular proliferation of the same grade of cytologic atypia between tumors with and without K-ras mutation (Ki-67 labeling index, high grade; 35.2 ±13.3% and 31.6±13.9%, low grade; 14.2±4.9% and 21.2± 12.8%, respectively). This indicates that mutation of K- ras codon 12 may be involved in the development of gallbladder carcinomas preferentially in patients with APBD, but not in the progression of the Ki-67 labeling index, tumor size, or tumor invasion.

Glucagon-like peptide-1 (GLP-1) has a potent glucose-dependent insulin secretory effect, and is thought to play an important role in regulating blood glucose levels as an "Incretin". In the early stage of non-insulindependent diabetes mellitus (NIDDM), impaired glucose-regulated insulin secretion in the rapid phase is a common feature. This feature is regarded to be partly due to defects in the biological actions of GLP-1, which are mediated by the GLP-1 receptor. Thus, defects in the islet B cell GLP-1 receptor gene may contribute to NIDDM. To test this hypothesis, we examined the association of the reported simple tandem repeat polymorphism (STRP) in GLP-1 receptor gene with NIDDM in Japanese. Genomic DNAs were extracted from peripheral blood leukocytes obtained from 24 independent NIDDM patients as well as 31 independent normal control subjects. The DNA fragments containing the reported STRP region were amplified by PCR. The sizes of the amplified DNA fragments varied between 108 to 122 bp (corresponding to 17 to 24 CA repeats); accordingly 8 different alleles were observed. The allelic frequencies did not differ between the Japanese NIDDM patients and the control subjects. These results indicate the absence of any obvious association of GLP-1 receptor gene STRP with NIDDM in Japanese.

Diagnostic conization is performed especially in the case of endocervical lesions with early cervical neoplasia because it is diffiucult to biopsy endocervical canal lesions in such cases. We analyzed the indications and usefulness of diagnostic conization by comparing its results with those of preoperative cytology and histology. The subjects consisted of 69 patients who underwent diagnostic conization at our hospital between January 1, 1988 and August 31, 1995. Preoperative histology by biopsy showed under diagnosis in 34 (49.3%), and over diagnosis in 16 (23.2%) compared with the diagnosis by conization, respectively. When the cytology indicated mild or moderate dysplasia and biopsy indicated moderate dysplasia or a less advanced lesion, no diagnostic conization was required because the final diagnosis bore out the earlier indications. When the cytology indicated carcinoma in situ (CIS) or invasive cancer, diagnostic conization was required because CIS or microinvasive cancer was ultimately diagnosed even if the biopsy showed no neplastic change. When the cytology indicated severe dysplasia to invasive carcinoma, 18.2% of the patients diagnosed as moderate dysplasia or a less advanced lesion by conization did not undergo hysterectomy. This study showed indication for diagnostic conization and the usefulness of conization for the reservation of the uterus.