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It has been reported that time to peptic ulcer healing is shorter with proton pump inhibitors (PPI) than with H2-receptor antagonists (H2-RA). This study was designed to examine the difference in the healing process between gastric ulcers treated with PPI and those treated with H2-RA.The healing of deep gastric ulcers treated with PPI (n = 11) or H2-RA (n = 13) was evaluated with endoscopic ultrasonography (EUS). Every 2 weeks during treatment EUS variables such as the width and the depth of the ulcer crater, the thickness and size of the low echoic area of the ulcer base, and the distance of the disrupted muscularis propria were measured. The contraction rates of EUS variables, the ratios of the contraction rate of the depth to that of the width of the ulcer crater (D/W ratio) and the contraction rate of the distance of the disrupted muscularis propria layer to that of the width of the ulcer crater (Dm/W ratio) were calculated.Only at week 2 were the D/W ratio and Dm/W ratio significantly higher in the group receiving PPI (D/W ratio, 1.79 +/- 0.701; Dm/W ratio, 0.938 +/- 0.207) than in the group receiving H2-RA (D/W ratio, 1.10 +/- 0.559; Dm/W ratio, 0.641 +/- 0.166).This study demonstrated that PPI therapy is associated with more rapid and stronger healing than obtained with H2-RA during the early treatment period.

To clarify the cellular differentiation of colorectal villous tumours in malignant transformation, compared with that of tubular tumours (tubular adenoma and adenocarcinoma arising in tubular adenoma).Forty-nine cases of colorectal villous tumours [six cases of low-grade villous adenoma, 21 of high-grade villous adenoma (VA), nine of invasive carcinoma in villous adenoma (CIVA), and 13 of pure villous carcinoma (PVC)] and 46 cases of tubular tumours [14 cases of low-grade and 17 of high-grade tubular adenoma (TA), and 15 cases of carcinoma in tubular adenoma (CITA)] were selected for this study based on their expression patterns of CD10 (small intestinal brush border), MUC2 (intestinal goblet cell), and HGM (gastric foveolar epithelium). HGM was more frequently expressed in the adenomatous components of villous tumours (63%) than in those of tubular tumours (14%) (P0.05). CD10 expression of high-grade TAs (47%) and carcinomas arising in TA (60%) was significantly higher than that of villous tumours (0%) (P0.05).There were significant differences in the phenotypic expression of adenoma and adenocarcinoma between villous and tubular tumours, respectively. Villous tumours have a pathway of malignant transformation different from that of tubular tumours. Because of biological differences, colorectal villous tumours should be distinguished from tubular neoplasia. The analysis of the phenotype of colorectal neoplasms is useful for the evaluation of tumour progression.

A 66-year-old male, whose primary skin lesion in extramammary Paget's disease had been surgically resected 4 years previously, was hospitalized with liver metastases. Hepatic arterial infusion chemotherapy was carried out and the tumours clearly reduced in size. Serum levels of some common tumour markers were not elevated, even prior to therapy. We measured serum levels of a novel tumour-associated antigen, RCAS1, because its expression was detected in the tumour cells. The patient's serum RCAS1 level was elevated (22.0 U/mL) before therapy and fell during (10.5 U/mL) and after (5.0 U/mL) therapy. Therefore, serum RCAS1 levels may be valuable as a potential biomarker for monitoring therapeutic efficacy against Paget's disease.

Primary hepatic carcinoid tumor (PHCT) is a extremely rare. The authors describe a patient with PHCT and review previously published cases of the disease.A 75-year-old man, presenting with weight loss and pain in the right upper abdomen, had multiple masses in both lobes of the liver. He was diagnosed as PHCT by radiological examination, laboratory findings with high levels of 5-hydroxyindoleacetic acid (5-HIAA) in the serum and urine, and histological findings including positive staining of tumor cells for Grimelius and chromogranin A. The patient received totally transcatheter arterial chemoembolization (TACE) five times over 27 months; this treatment provided excellent palliation and caused a decrease in urinary 5-HIAA levels. Fifty-three cases of PHCT have been reported in the English-language literature.Analysis of these published cases revealed that PHCT occurs in the middle age (mean age = 48.2 years) and is more frequent in females (males/females = 20/33 cases). Of the symptomatic patients, the major findings is abdominal pain, fullness, and/or a palpable mass (56% of symptomatic patients). In contrast, only 2 cases out of 53 presented with symptoms of typical carcinoid syndrome. In most cases, PHCT was detected as a hypervascular lesion by radiological examination. By histological analysis, 80% and 84% of the cases were positive for Grimelius silver stain and immunohistochemically positive for chromogranin A, respectively. Surgical resection is the treatment primarily recommended with an 18% of recurrence rate and a 74% of a survival rate after 5 years. For unresectable and recurrent cases, TACE may be recommended.

The elevated serum leptin level of patients with alcoholic cirrhosis has been reported, however, the precise mechanism is still unknown. Leptin expression and protein synthesis have also been detected in activated hepatic stellate cells in cell cultures, which play a major role in hepatic fibrosis. We evaluated the serum leptin levels of patients with nonalcoholic liver diseases including cirrhosis and chronic hepatitis. We also investigated the hepatic clearance of leptin by determining the serum leptin level in blood samples obtained from the portal and hepatic veins.The serum leptin level of 44 patients with nonalcoholic chronic liver disease (male/female = 21/23, cirrhosis/chronic hepatitis = 30/14) and 40 control subjects (male/female = 20/20) was determined in blood samples obtained from the antecubital vein by enzyme-linked immunosorbent assay. We also assessed the relationship between the leptin level and various biochemical tests of liver function. Additionally, we determined the leptin levels in the portal and the hepatic venous blood (nonalcoholic cirrhosis = 10, nonhepatic disease = 4).There were positive correlations between the serum leptin level and body mass index among males and among females in the liver disease group and in the control group. However, the serum leptin level of the liver disease group and control group did not differ significantly. Among the 44 liver disease patients, only the serum cholesterol level was significantly correlated with the serum leptin level after adjusting for sex and body mass index by multiple regression analysis. Furthermore, the leptin level in hepatic venous blood was significantly lower than that in portal venous blood. However, the ratio of [leptin level in hepatic venous blood]/[leptin level in portal venous blood] in the cirrhosis group, and that in the nonhepatic disease group, did not significantly differ.The serum leptin level of patients with nonalcoholic liver diseases is not elevated. On the other hand, the serum leptin level of patients with alcoholic cirrhosis has been reported to be elevated. The difference in the serum leptin level of patients with nonalcoholic liver disease and that of patients with alcoholic cirrhosis may be due to a difference in factors such as the levels of cytokines or sex steroids, and/or nutrition. Furthermore, it is likely that leptin is cleared in part by the portosystemic circulation through the liver.

In this study, five single clones were randomly established by limiting dilution method from each of the HTLV-I positive T cell lines - HUT 102 and ATL-2, and examined for the all-trans retinoic acid (ATRA) sensitivity, respectively. For each clone, we found a significant correlation between the reduction in 3[H]-thymidine incorporation and the reduction in CD25 expression (r=0.701, P0.05) following treatment with 10(-5) M ATRA for 48 h. Agarose gel electrophoresis revealed DNA fragmentation of the cell lines treated with ATRA, indicative of apoptosis. These results suggested that the tax gene in the HTLV-I genome might be a key molecule involved in cell proliferation and CD25 expression. Thereafter, we transfected the tax gene in the expression vector (pCMV-Tax-neo) into the HTLV-I(-) T cell line Jurkat and examined the effects of ATRA on cell growth. The results showed that ATRA sensitivity was acquired by the Jurkat cells transfected with the tax gene expression vector, but not in those transfected with the control vector. We also observed NF-kappaB transcriptional activity on Jurkat cells transfected with the tax gene by CAT assay in the presence or absence of ATRA. NF-kappaB transcriptional activity was decreased significantly on Jurkat cells transfected with the tax gene after ATRA treatment. Taken together, these results indicate that ATRA may affect or block the Tax/NF-kappaB signaling pathway in ATL cells.

Several pretreatment factors have been reported to be useful in predicting patients with a high probability for a sustained response to IFN-alpha treatment, however, predictors of the efficacy of interferon-beta treatment in chronic hepatitis C have not been fully assessed.To clarify this issue, a prospective study of 52 patients with chronic hepatitis C was conducted. Patients were treated with human natural interferon-beta by drip infusion at doses of 6 MU/day for 8 weeks. The following characteristics were compared between patients with sustained response (SR) and no response (NR): gender, age, source of HCV infection, mean pretreatment serum ALT levels, liver histology, pretreatment serum HCV-RNA levels and HCV genotype.Seventeen of 52 patients (32.7%) demonstrated SR. The proportion of patients with undetectable HCV-RNA levels determined by branched DNA assay (0.5 x 10(6) eq/ml) was higher in patients with SR than in those with NR (88.2% vs. 22.9%; p = 0.0001). Pretreatment HCV RNA levels determined by multicyclic reverse transcriptase polymerase chain reaction were lower in patients with SR than in those with NR (10(5.1 +/- 1.5) vs. 10(7.1 +/- 1.3) copies/ml; p = 0.0001). The rate of SR was higher in patients with genotype 2a or 2b than in genotype 1b (43.8% vs. 15.0%; p = 0.0382). Multivariate stepwise logistic regression analysis showed that a younger age and low pretreatment serum levels of HCV RNA were independent predictors of SR to treatment. This prospective study demonstrated that a younger age, low pretreatment viral load and HCV genotype 2a or 2b were factors influencing the SR to interferon-beta treatment, but a younger age and low pretreatment viral load were most important predictors of the efficacy of the treatment.

Among 326 consecutively resected cases of hepatocellular carcinoma (HCC), we studied clinicopathologic features of 13 cases (NBNC-HCC) negative for hepatitis B surface antigen (HBsAg), antibody to HBsAg (HBsAb), antibody to hepatitis B core antigen (HBcAb), hepatitis B envelope antigen (HBeAg), antibody to HBeAg (HBeAb), and antibody to hepatitis C virus (HCVAb). Forty-four HCC cases positive only for HBsAg (B-HCC) and 232 cases positive only for HCVAb (C-HCC) were studied as controls. Clinically, NBNC-HCC cases showed good liver function reserve. None of NBNC-HCC cases had periodic medical check ups and HCC was detected in 12 cases (92.3%) incidentally. Pathologically, the mean tumor diameter was significantly larger and the histologic grade was less differentiated in NBNC-HCC cases than in B-HCC and C-HCC cases. In the background liver, liver cirrhosis was associated in 15.4% of NBNC-HCC cases, 50.0% of B-HCC and 38.2% of C-HCC cases. The degree of inflammation and fibrosis was less in NBNC-HCC cases, and two cases (15.4%) had almost normal liver histology. In NBNC-HCC cases, synchronous and metachronous multicentric occurrence was not observed. In B-HCC cases, synchronous multicentric occurrence was found in 1 case (20.0%), but no metachronous multicentric occurrence. In C-HCC cases, synchronous and metachronous multicentric occurrence was found in 13 (43.3%) and 8 (30.8%) cases, respectively. However, the cumulative recurrence-free rate was not significantly different among the three groups. Accordingly, it was suggested that better prognosis could be expected in NBNC-HCC cases compared with B- and C-HCC cases, if the cancer could be detected in the early stage.

To clarify the contribution of the inhibin-like immunoreactivity (inhibin-LI) produced by adrenal glands to the total circulating levels of inhibin-LI, we measured serum inhibin-LI in normal and hypogonadal subjects under ACTH-loading or dexamethasone-loading condition. The mean basal concentration of inhibin-LI in the peripheral serum of the hypogonadal cases was 3.6 +/- 1.3 IU/ml (mean +/- SD, n = 5), which corresponded to 19.5 +/- 5.8% of that of normal controls matched for age and sex. The low levels of inhibin-LI in hypogonadal subjects (n = 7) rose significantly (3.6 +/- 1.1 vs 8.1 +/- 1.7 IU/ml, p0.001) after the administration of synthetic 1-24ACTH (40 units/day intramuscular injection) for 2 days, while the levels of serum inhibin-LI were not increased in two cases of Addison's disease with hypogonadism after the administration of ACTH. After the oral administration of a low dose of dexamethasone (1 mg) the serum inhibin-LI level in normal subjects (eight males and eight females) decreased significantly (male, 16.2 +/- 3.3 vs 14.5 +/- 4.1 IU/ml; female, 12.9 +/- 6.3 vs 10.8 +/- 5.6 IU/ml; p0.01 each) without significant change in the levels of serum gonadotropin (LH and FSH) and those of gonadal steroid (testosterone or estradiol). These results indicate that a small; but significant amount of inhibin-LI is secreted from the adrenal gland and circulating in vivo, and that the proportion of adrenal-derived inhibin-LI is much higher in patients with hypogonadism.

To clarify whether the response of host cellular immunity to IFN therapy can be an indicator of efficacy, we monitored serum levels of soluble IL-2 receptor (sIL2R) before and after IFN therapy.Serum sIL2R levels before and after interferon therapy were monitored in 53 patients with chronic hepatitis C. Natural Interferon(IFN)-alpha, 9 MU/day (everyday for 2 weeks followed by 3 times/week for 22 weeks), was administered to all patients.After the IFN therapy, sIL2R levels were significantly increased (before, 403.4+/-221.1 U/mL, and after, 542.0+/-307.6 U/mL, p0.01). The patients were divided into two groups: the complete response (CR) group who were negative for serum hepatitis C virus (HCV)-RNA 6 months after the therapy, and the recurrence group who were positive for HCV-RNA 6 months after the therapy. Between these two groups, sIL2R levels before therapy were not significantly different, and sIL2R levels after therapy were also not significantly different. Although the ratio of sIL2R levels before and after was monitored, there was no significant difference between the CR group and recurrence group ((sIL2R after IFN)/(sIL2R before IFN)): 1.39+/-0.65 in the CR group and 1.99+/-2.07 in the recurrence group).sIL2R increased due to IFN administration, but it is not a good indicator for the efficacy of IFN therapy. It seems that the response of cellular immunity to IFN therapy does not play an important role in its efficacy.

Rapid atrial pacing in sinus rhythm may directly induce atrial flutter without provoking intervening atrial fibrillation, or initiate atrial flutter indirectly, by a conversion from an episode of transient atrial fibrillation provoked by rapid atrial pacing. The present study was performed to examine whether or not the direct induction of clockwise or counterclockwise atrial flutter was pacing-site (right or left atrium) dependent.We analyzed the mode of direct induction of atrial flutter by rapid atrial pacing. In 46 patients with a history of atrial flutter, rapid atrial pacing with 3 to 20 stimuli (cycle length = 500 - 170 ms) was performed in sinus rhythm to induce atrial flutter from 3 atrial sites, including the high right atrium, the low lateral right atrium, and the proximal coronary sinus, while recording multiple intracardiac electrograms of the atria. Direct induction of atrial flutter by rapid atrial pacing was a rare phenomenon and was documented only 22 times in 15 patients: 3, 11, and 8 times during stimulation, respectively, from the high right atrium, low lateral right atrium, and the proximal coronary sinus. Counterclockwise atrial flutter (12 times) was more frequently induced with stimulation from the proximal coronary sinus than from the low lateral right atrium (8 vs 1, P = .0001); clockwise atrial flutter (10 times) was induced exclusively from the low lateral right atrium (P = .0001 for low lateral right atrium vs proximal coronary sinus, P = .011 for low lateral right atrium vs high right atrium).Direct induction of either counterclockwise or clockwise atrial flutter was definitively pacing-site dependent; low lateral right atrial pacing induced clockwise, while proximal coronary sinus pacing induced counterclockwise atrial flutter. Anatomic correlation between the flutter circuit and the atrial pacing site may play an important role in the inducibility of counterclockwise or clockwise atrial flutter.

We report a case of giardiasis in the pancreas in a patient with diabetes mellitus. The patient is interesting in the following: 1) Giardia lamblia was found only in the pancreas and not in the gall bladder by cytology on endoscopic retrograde cholangiopancreaticography (ERCP) and by cerulein-secretin test (CST). 2) ERCP revealed multiple small cysts scattered throughout the pancreas. 3) Decreased pancreatic exocrine function was recovered by treatment with metronidazole.

The most common forms of chronic pancreatitis are related to alcohol ingestion, whereas the entity of non-alcohol-associated (idiopathic) pancreatitis is poorly understood. Autoimmunity has been suggested as a possible etiologic factor of idiopathic chronic pancreatitis. A total of 362 Japanese patients underwent endoscopic retrograde pancreatography (ERP) for suspected pancreatic disease, and 161 were diagnosed with chronic pancreatitis. Among them, we found three cases (1.86% incidence) of unique chronic pancreatitis, in which ERP revealed diffuse narrowing of the main pancreatic duct with an irregular wall. We diagnosed these three patients as having pancreatitis associated with an autoimmune mechanism morphologically and biochemically and started them on steroid therapy. The characteristics of the these three patients were as follows: hypergammaglobulinemia, eosinophilia, ultrasonography showing hypoehoic diffuse swelling in the pancreas (sausage-like appearance), ERP showing diffuse narrowing of the main pancreatic duct with irregular like thumbprint-like marks, reversible exocrine insufficiency, and positive anti-carbonic anhydrase II antibody. After one month of the treatment with steroids, pancreatitis dramatically improved morphologically and enzymatically. Here we describe these cases of the suspected autoimmune chronic pancreatitis. We must recognize the concept and the features of autoimmune pancreatitis in order to avoid unnecessary surgery as pancreatic cancer.

Serum 7B2 concentrations in control subjects and patients with diabetes mellitus were measured following a 75 g oral glucose load and following intravenous glucagon infusion. In response to oral glucose, serum 7B2 levels increased in the controls (n = 10) and in the diabetic patients (n = 7). The increment of the serum 7B2 level was smaller in the diabetic patients than the controls. During the 75 g oral glucose tolerance test (75g OGTT), serum 7B2 levels were significantly positively correlated with serum C-peptide levels. In contrast, following intravenous glucagon infusion, serum 7B2 levels increased only in diabetic patients treated with oral hypoglycemic agents (n = 20) and did not increase in controls (n = 5): the group having the highest insulin secretion activity in the present study, nor in diet or insulin-treated diabetic patients. No correlation between serum 7B2 levels and serum CPR levels was observed in the intravenous glucagon infusion study. These data suggest that an extra-pancreatic source which produces the observed serum 7B2 increase following oral glucose intake can not be excluded and that 7B2 may not be secreted concomitantly with insulin from the pancreatic beta cell in response to intravenous glucagon injection.

The endoscopic ultrasonography (US) characteristics of early scirrhous carcinoma of the stomach (ESS) were evaluated in four patients. ESS was defined as the presence of poorly differentiated carcinoma cells spreading through the submucosa and muscularis propria in association with a marked desmoplastic reaction without serosal invasion. ESS was characterized by localized irregular hypoechoic enlargement of the third (submucosal) and the fourth (muscularis propria) layers. The fifth (serosal) layer was normal. The third and fourth layers showed a threefold increase in thickness compared with the thickness of these layers in healthy subjects. Our results suggest that endoscopic US is useful for diagnosis of ESS.

A rare case of severe small bowel hemorrhage due to jejunal metastases from a large-cell type carcinoma of the lung is reported. A 69-yr-old Japanese woman presented with complaints of mild abdominal pain and liquid tarry stools 6 months following surgery for lung carcinoma. Gastroduodenoscopy and barium enema yielded unremarkable findings, although a subsequent small bowel enema revealed a large, 15-cm ulcerated mass in the jejunum. This tumor was resected and histology confirmed to be consistent with a metastasis from the primary undifferentiated large-cell carcinoma of the lung. The patient had an uneventful postoperative course and survived for 9 months. There have been only two prior case reports of major intestinal hemorrhage secondary to pulmonary carcinoma metastases in the English literature. Previous reports of such metastases of the small bowel have bowel have documented a very poor prognosis and our patient demonstrated the longest survival period to date. The clinical course of this patient suggests that the early diagnosis and palliative surgery for this complication provide a more favourable outcome.

Lck protein is expressed in some colon carcinoma cell lines but its expression in colon cancer cells in vivo has not been clarified. LCK transcription is regulated from two distinct promoters and initiated exclusively from the downstream promoter in colon carcinoma cell lines in contrast to peripheral lymphocytes. We investigated the expression of the downstream promoter-initiated LCK transcript in 18 colorectal primary cancer and normal mucosae, and two hepatic metastases, using a RNase protection assay with the Eco RI- Bgl II fragment of human LCK cDNA, YT16. In normal tissues, only traces of the LCK transcript were detected. The expression of the LCK transcript was augmented in 318 cancer specimens. The relative level of the LCK transcript in the cancer tissue compared to the average value of normal adjacent tissue was 10–60 in 3 cases, and 3–10 in 7 cases. One hepatic metastasis expressed more LCK message than the primary lesion. Our results indicate that the LCK message is strongly expressed in some colorectal cancers.

This is the first case of primary macroglobulinemia with t(11;18) (q21;q21) reported in the literature. A 77-year-old man was admitted to a hospital in December, 1994, with acute renal failure and pleural effusion. He was treated with prednisolone pulse therapy and his symptoms improved. He was referred to our hospital for further examination. Analysis of blood chemistry revealed macroglobulinemia (IgM-kappa). There were no other findings that would indicate a diagnosis of malignant lymphoma. A complete blood count revealed a hemoglobin level of 8.7 g/dl and a white blood cell count of 5,300/microliters with 11% abnormal lymphoid cells. Immunologic and karyotype analyses revealed that these abnormal cells were positive for IgM-kappa, CD19, and CD20, negative for CD5, and CD10, and had t(11;18) (q21;q21). The bone marrow had also been infiltrated by 8.6% abnormal lymphoid cells. Six other cases with t(11;18) (q21;q21) have been reported including 5 of small lymphocytic lymphoma and 1 of mucosa-associated lymphoid tissue-type lymphoma. The tumor cells in these cases were the same as in our case. Therefore, our report is in agreement with the finding that t(11;18) (q21;q21) might be one of the characteristic chromosomal abnormalities in mature B-lymphoid neoplasms.

We compared the etiology and prognosis of liver cirrhosis in patients age 60 and older with that of patients under age 60 during the 1980s (1981-89, n = 207). Non-A, non-B hepatitis (NANB) was significantly more prevalent in the elderly (p0.05), and the mean age of NANB and alcoholic cirrhosis (Alc) were significantly older than those with hepatitis B virus (HBV) (p0.05). Evaluation using hepatitis C virus (HCV) antibody also revealed significantly higher mean age of HCV (p0.05). Male patient was predominant in the younger patients than in the elderly patients. (M/F = 2.94 and 1.33, respectively) The estimated 5-year survival rate was 73.1% in the younger patients and 60.2% in the elderly patients (p0.05). Multivariate analysis revealed that male sex, a lower serum albumin level, and the presence of the encephalopathy were significantly associated with poor prognosis in the elderly, while a lower serum cholinesterase level and a higher indocyanin green retention rate at 15 minutes (ICGR15) were significantly associated with poor prognosis in younger patients. However, causes of deaths were not significantly different between the younger patients and the elderly patients, the proportion of deaths unrelated to liver disease predominated in the elderly patients. Thus, the etiology and the prognostic factors of liver cirrhosis in elderly patients differ from those in younger patients.

To examine bile acid synthesis in chronic liver diseases, serum total 7 alpha-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry in patients with cirrhosis (n = 23), patients with chronic hepatitis (n = 21), and control subjects (n = 18). The serum 7 alpha-hydroxycholesterol levels were significantly lower in patients with cirrhosis than the controls (78 +/- 59 pmol/mL vs. 237 +/- 97 pmol/mL; mean +/- SD). However, in patients with chronic hepatitis, the level was fully retained (262 +/- 102 pmol/mL). Serum 7 alpha-hydroxycholesterol levels of 17 patients with cirrhosis classified as Child B and C ranged from 33 to 69 pmol/mL, and all were less than the normal range (between 104 and 466 pmol/mL), however, those levels of some patients classified as Child A were within the normal range. Serum 7 alpha-hydroxycholesterol levels significantly correlated with serum albumin, cholinesterase, total bile acid, direct bilirubin, alkaline phosphatase, indocyanine green (ICG) retention rate, hepaplastin test, and lecithin-cholesterol acyltransferase activities. We conclude that bile acid synthesis is well preserved in patients with chronic hepatitis and that it is decreased in most patients with cirrhosis. Serum 7 alpha-hydroxycholesterol may be a new parameter of liver function testing to assess hepatic bile acid synthesis in patients with chronic liver diseases.

We report here the establishment and characterization of a human melanoma cell line derived from the ascitic fluid of a patient with metastatic malignant melanoma with peritonitis carcinomatosa. This cell line was easily transplanted into nude mice. Flow cytometry and immunocytochemical analyses demonstrated that the cells expressed melanotransferrin and S-100 protein. Expression of cell adhesion and HLA molecules on the cells was also investigated. The results indicate that the cell line possesses some metastatic characteristics.

Using endoscopic ultrasonography, we diagnosed a gastric antral submucosal cyst with a papillous protrusion in a 71-yr-old woman, apparently the first such case to be detected by this method. Endoscopic ultrasonography demonstrated a well-marginated hypoechoic area with papillary tumor in the submucosal layer that did not extend to the muscularis propria. The lesion was diagnosed as a gastric submucosal cyst. CT and transabdominal ultrasound each failed to detect the intracystic papillary tumor. Follow-up endoscopic ultrasonography performed 6 months later revealed an increase in the diameter of the cyst and the papillary tumor. The patient then underwent a partial gastrectomy for a suspected malignancy. The resected specimen showed a cystic lesion with papillary tumor. Although no malignancy was present, examination of cross-sections of the resected specimen gave results consistent with the endoscopic ultrasonographic findings. Endoscopic ultrasonography is thus useful in assessing the nature of a submucosal gastric cyst in detail and in monitoring patients with this lesion.

In order to investigate the age-related changes in neuropeptide Y (NPY) in cerebrospinal fluid (CSF) of men and women, we examined the concentration of NPY-like immunoreactivity (NPY-LI) in CSF of a large population of Japanese men and women by specific radioimmunoassay (RIA). The dilution curve of CSF extract paralleled the standard curve of RIA for human NPY. Gel chromatographic studies revealed the presence of two peaks of NPY-LI, one emerging at the elution position of synthetic NPY and another emerging at a higher-molecular-weight position. NPY-LI in the CSF in 201 men (aged 17 to 69y) and 118 women (aged 17 to 69y) was 124 +/- 4 and 136 +/- 6 pg/ml (mean +/- SE), respectively. NPY-LI in the CSF of women, but not of men, increased significantly with aging. This finding suggests that the level of NPY with aging in the central nervous system (CNS) may be regulated somewhat differently in men and women.

All diabetic patients should be screened for the early stage of diabetic nephropathy, because microalbuminuria has a great prognostic significance. The albusure test (AT), alatex agglutination nephelometric immunoassay, is a rapid and low cost test for the detection of microalbuminuria of 30 mg/L or more. We compared the results of AT and of radioimmunoassay (RIA) for urinary albumin to evaluate the clinical utility of AT using fresh urine samples from 74 diabetic patients without persistent proteinuria and from 11 healthy subjects. Urinary albumin levels measured by RIA were 6.0 +/- 2.3 mg/L in the healthy subjects, 11.0 +/- 8.7 mg/L in the AT-negative group (n = 61), and 38.1 +/- 10.2 mg/L in the AT-positive group (n = 13). Using a cut-off value of 30 mg/L by RIA, the rate of coincidence between AT and RIA was 89.2%, although five subjects were false-positive by AT, and three were false-negative. These results show that AT may provide a useful monitor microalbuminuria, a reliable early mark of diabetic nephropathy.

We report unique features of computed tomography (CT) and magnetic resonance (MR) imaging in the metastatic lesion of the liver in a case of gastric leiomyosarcoma. A CT scan and MR image demonstrated presence of a huge multilocular cystic lesion in the liver, of which finding were unlike to those of usual smooth muscle tumors, but mimicked to those of cystadenomatous tumors. In addition, this case had an extremely long elapsing time over ten years from the radical operation for the primary site.

We examined the serum levels of testosterone (T), androstenedione (delta 4-A), estrone (E1), estradiol (E2), and dehydroepiandrosterone sulfate (DHEA-S) in the non-alcoholic cirrhotic male patients when divided into compensated or decompensated state. Serum level of T was significantly elevated in compensated cirrhotic patients (9.63 +/- 1.00 ng/ml, mean +/- SE) compared to that in decompensated cirrhotic patients (5.63 +/- 0.69 ng/ml, p0.01) and in aged-matched normal controls (4.95 +/- 0.38 ng/ml, p0.01). Serum levels of E1, E2 and delta 4-A tended to be increased in decompensated cirrhotic patients, while there was not a significant difference decompensated cirrhosis compared to those of normal controls. Serum concentration of cholinesterase, indicative one of the representative residual liver function, showed a good positive correlation to T (r = 0.53, p0.01), and a negative correlations to E1 (r = -0.67, p0.01), E2 (r = -0.77, p0.01), delta 4-A (r = -0.57, r = p0.01). Also, we examined the relationship of the serum levels to gynecomastia or esophageal varices. The cirrhotics with gynecomastia showed significantly higher serum levels of E1, E2, and delta 4-A, and lower level of T than those without gynecomastia. And the cirrhotics with esophageal varices showed the greater level of T than those without esophageal varices. Our study suggests that low serum testosterone level of men with nonalcoholic cirrhotic is not a common finding, especially in compensated state.(ABSTRACT TRUNCATED AT 250 WORDS)

To clarify the Sertoli cell and Leydig cell function in hypogonadic male patients with myotonic dystrophy (DM), serum concentrations of inhibin, total testosterone (TT), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay in 6 male DM patients (41 to 56 years old, 47.7 +/- 5.05 years old) and compared with those in normal adult men. In 116 healthy men aged from 24 to 92 years, serum inhibin and TT levels decreased and serum FSH and LH concentrations increased with advancing age. There was an inverse correlation between serum inhibin and FSH. These results support the concept of negative feedback regulation system of FSH secretion by inhibin. Male DM patients showed significantly lower serum TT and higher concentrations of FSH and LH, compared with the age-matched 39 normal adult men (49-59 years old, 48.2 +/- 6.14 years old). However, there was no significant difference in serum inhibin levels between the patients and normal counterparts. These results indicate that the Sertoli cell function is reserved in male DM patient, although the Leydig cell function is impaired. It is also suggested that in these patients a negative feedback control system between inhibin and FSH may be disordered to some extent.

Partial ophthalmoplegia due to third nerve palsy with an intact pupil is a frequent cause of diploplia observed in diabetic patients. Pupillary muscle involvement, such as anisocoria and loss of light reflex, is usually uncommon in this diabetic cranial mononeuropathy. A 65-year-old woman with non-insulin dependent diabetes mellitus (NIDDM) suddenly developed a severe headache and diplopla. Right oculomotor nerve palsy was observed in association with anisocoria, ptosis of the right lid, and a defective light reflex. No exophthalmos or vascular bruit was observed in the right orbital region. Computed tomography and magnetic resonance images of the head were negative. Cerebral angiography revealed a carotid cavernous sinus fistula (CCF). The patient was successfully treated with external carotid artery embolization combined with radiation. It is well known that pupil sparing in oculomotor nerve palsy predicts an extraaxial ischemic lesion, while pupil involvement predicts an extraaxial compression lesion. Therefore, pupillary involvement in oculomotor nerve palsy in diabetic patients necessitates cerebrovascular investigation to rule out ICPC aneurysm or tumor. In this circumstance, a variant type of CCF without characteristic ocular signs should be included in the differential diagnosis.

The plasma levels of endothelin-like immunoreactivities (ET-IR) of patients with hepatocellular carcinoma (HCC) were compared with those of patients with liver cirrhosis (LC), using a specific radioimmunoassay for endothelin-1. The mean concentration of plasma ET-IR of 21 HCC patients (30.3 +/- 8.5 pg/ml, n = 21) (means +/- SD) was markedly higher than those in LC (22.1 +/- 4.7 pg/ml, n = 16) (p0.01), which were also elevated compared with those in normal subjects (9.4 +/- 1.6 pg/ml, n = 91). Moreover, the level of plasma ET-IR reflected the tumor size of HCC patients, which was estimated by the ultrasonic and computed tomographic examinations. Although there was no relation to other biochemical parameters indicating liver function or tumor markers such as alpha-fetoprotein, a good positive correlation was obtained between plasma ET-IR and C-reactive protein (CRP) concentrations of HCC patients (r = 0.805, p0.01). We measured the tissue contents of ET-IR in HCC and its adjacent LC tissue, but failed to find any significant difference between the mean content of HCC (0.50 +/- 0.38 ng/g) and LC (0.44 +/- 0.28 ng/g). The endothelial cell damage due to cancer growth may not be responsible for the high concentrations of plasma ET-IR of HCC, because plasma thrombomodulin concentrations were not correlated with plasma ET-IR levels in HCC patients. Our study implies that the high plasma concentration of ET-IR is pathogenomonic to HCC, although the site of production is still debatable.

All diabetic patients should be screened for early signs of diabetic nephropathy, because it is a prognostic factor in the disease. The albusure test (AT), a latex agglutination nephelometric immunoassay, is a rapid and low cost test for the detection of microalbuminuria of 30 mg/L or more. We compared the results of AT and of radioimmunoassay (RIA) for urinary albumin to evaluate the clinical utility of AT using fresh urine samples from 74 diabetic patients without persistent proteinuria and from 11 healthy subjects. Urinary albumin levels were 6.0 +/- 2.3 mg/L in the healthy subjects, 11.0 +/- 8.7 mg/L in the AT-negative group (n = 61), and 38.1 +/- 10.2 mg/L in the AT-positive group (n = 13). Using a cut-off value of 30 mg/L by RIA, the rate of coincidence between AT and RIA was 89.2%, although five subjects were false-positive by AT, and three were false-negative. These results show that AT may provide a useful monitor for microalbuminuria, a reliable early marker of diabetic nephropathy.

Osteoporosis is now one of the most serious problems in aged Japanese women. We investigated bone mineral contents of the vertebrae of 132 adult women (28-94y.o.) using dual energy X-ray absorptiometry (DEXA) in order to clarify the change of the bone mineral densities (BMD) with aging, and the influences of a diet and exercise on osteoporosis. In the women, BMD of the vertebrae increase to maximum level in 3 rd or 4 th decade of life, and then reduce with aging. The level of BMD is well matched with the index of osteopenia using the lateral view of vertebral X-ray. According as the BMD reduce, the number of bone fractures and the number of patients with bone fractures increase. More than 80% of the women whose BMD are less than 0.7 g/cm2 have bone fractures. In aged women, over 65 year's old, exercise had significant positive effect with BMD, but that was no evidence for influence of calcium intake to BMD.

A 76-year-old man was admitted because of general fatigue and lumbago. Two years before admission, hyponatremia and hyperkalemia were pointed out, subsequently hydrocortisone (20 mg/day) was given under the diagnosis of panhypopituitarism. The marked improvement was found in the electrolytes abnormality. On examination at admission, there was no abnormality of anterior pituitary function. In addition to the extremely low level of plasma renin activity and aldosterone concentration, the persistent microhematuria and hyperuricemia were found, however, renal histology only showed the benign arteriosclerosis but no significant alteration in juxtaglomerular apparatus and glomeruli. The urinary prostacyclin metabolite output was rather increased compared to that of normal subject, suggesting that prostaglandins may not be responsible for the defect of renin secretion. Although, the cause was still unknown, small dose of dexamethasone was extremely effective to resolve electrolytes abnormality and hematuria.

Here we report a rare case of simple hepatic cysts causing dilatation of the intrahepatic bile duct. A 75-year old female was admitted to Kyushu University Hospital because of liver dysfunction. Ultrasonogram and CT scan showed two neighboring cysts in the liver (S2, S4), and dilatation of the peripheral bile duct in left lateral segment of the liver. Echo-guided percutaneous aspiration of cyst fluid showed the elevated levels of CA19-9, but malignant cell were not seen. These findings suggested that the compression by these neighboring simple hepatic cysts caused the stenosis of the bile duct. The dilatation of the bile duct disappeared after the percutaneous ethanol sclerosing therapy for cyst.

The usefulness of endoscopic ultrasonography (EUS) was assessed for diagnosing the depth of invasion in the gastric wall, the infiltration to the adjacent organs, and detecting regional lymph node involvement in primary gastric lymphoma. EUS was performed in 11 patients with primary gastric lymphoma who subsequently underwent gastrectomy with lymph node dissection, as well as chemotherapy in some cases. EUS findings showed a good correlation with the histopathology of the resected specimens. An accurate diagnosis of the depth of invasion into the gastric wall was made in 10 of 11 patients using the same T grade of the 1987 TNM system for gastric carcinoma. EUS also clearly visualized the reduction of depth of tumor invasion in two patients who underwent chemotherapy. Perigastric lymph node involvement could be detected accurately in nine of 11 patients. In conclusion, EUS is an excellent and sensitive diagnostic modality for the preoperative staging and follow-up of primary gastric lymphoma.

We conducted case-control studies of hepatocellular carcinoma (HCC) and liver cirrhosis (LC) in relation to hepatitis C virus (HCV) and hepatitis B virus infection, involving 91 patients with HCC, 75 patients with LC who had no evidence of HCC, and 410 control subjects from the Japanese population. Serum antibody to HCV (anti-HCV) was detected by both enzyme-linked immunosorbent assay and recombinant immunoblot assay in 51, 51, and 3% of HCC, LC, and controls, respectively, whereas the corresponding prevalence of serum hepatitis B surface antigen (HBsAg) was 21, 11, and 2%, respectively. The relative risks (and 95% confidence intervals) for the presence of serum anti-HCV were estimated as 52.3 (23.9-114.3) for HCC and 64.4 (27.4-151.4) for LC. These values exceeded the relative risk of HCC (15.3) and that of LC (6.1) for positive serum HBsAg. Among male patients with HCC or LC, anti-HCV rates were very high in blood recipients (about 70%), heavy drinkers (46-62%), and those who had no identifiable risk factors (65-75%), indicating possible transmission of HCV via routes other than transfusion. No significant difference in anti-HCV status was observed between the HCC and LC groups. It was notable that anti-HCV was much less prevalent among HBsAg-positive patients with HCC or LC than among HBsAg-negative ones. There was a slight to moderate increase in HCC or LC risk among blood recipients and heavy drinkers after adjustment for anti-HCV status. These results indicate that, in Japan, the possible role of HCV infection in the etiology of HCC and LC is extremely large and seems to be more important than chronic hepatitis B virus infection.

A 74-year-old woman with a history of a benign gastric polyp was admitted to our hospital with a complaint of epigastric discomfort. A diagnosis of primary gastric lymphoma was confirmed by endoscopy and results of abrasive cytology. Endoscopic ultrasonography (EUS), performed prior to surgery, demonstrated clearly the submucosal invasion of the gastric lymphoma. Histopathology on the depth and the involvement of perigastric lymph nodes of surgical specimen confirmed the accuracy of the EUS findings. Thus EUS offers a means of early preoperative diagnosis and staging of gastric lymphoma, and that is superior to conventional endoscopy in such cases.

We report a patient who developed multiple liver abscesses and sepsis caused by lactobacilli after the percutaneous intratumoral injection of ethanol for hepatocellular carcinoma. We diagnosed the liver abscess at an early stage because of a the finding of gas on ultrasound and computed tomography. Blood cultures grew Gram-positive rods, which were of the Lactobacillus species. The patient responded to the administration of antibiotics, and his hepatic tumors have not recurred in the 7 months since treatment. This is the first report of liver abscess following percutaneous ethanol injection therapy.

We describe two cases of gastrointestinal lymphoma associated with rapid bone marrow dissemination after surgical resection. Case 1: A 73-year-old male was diagnosed as having malignant lymphoma originating from ileocaecal region (diffuse medium-sized, B cell type). Tumor (8 x 8 cm) was resected but infiltrated to the peritoneum and curative operation could not be done. Two weeks after operation, elevation of LDH, pancytopenia and bone marrow infiltration of lymphoma cells developed and he died of respiratory failure. Case 2: A 69-year-old female was diagnosed as having remnant gastric lymphoma (diffuse large, B cell type). Tumor size was 5 x 4 cm and swelling of the third lymph nodes was found, so curative operation could not be done. Two months after operation bone marrow infiltration of lymphoma cells was observed and she is now undergoing chemotherapy. Surgical resection is performed in the majority of patients with localized gastrointestinal lymphoma. But the operation of the advanced case must be carefully done, because the operative procedure may sometimes facilitate growth and metastasis of tumor.

To examine the interrelationship between human atrial natriuretic polypeptide (hANP) and cyclic 3'5'-guanosine monophosphate (cyclic GMP), plasma concentrations of these compounds were determined in 61 disease-free humans, as controls, and in 35 patients with congestive heart failure. Levels of plasma hANP (199.6 +/- 53.7 pg/ml) and cyclic GMP (12.6 +/- 1.7 pmol/ml) in patients with congestive heart failure were significantly higher than in the control subjects (hANP 57.1 +/- 2.8 pg/ml, cyclic GMP 5.2 +/- 0.3 pmol/ml). Although plasma hANP concentrations in the patients with congestive heart failure tended to increase with the severity of cardiac dysfunction, there was no significant correlation between the levels of plasma hANP and the grade of heart failure, classified according to the New York Heart Association. However, a significant correlation was found between plasma hANP and cyclic GMP concentrations in both the healthy subjects and the patients with congestive heart failure, and a weak positive correlation between plasma hANP and cyclic 3'5'-adenosine monophosphate (cyclic AMP) concentration in the patients with congestive heart failure. Thus, changes in plasma cyclic GMP concentration depend to some extent on the plasma concentrations of hANP.