Kohei Katsumi

Physiological concentrations of human epidermal growth factor in biological fluids: use of a sensitive enzyme immunoassay

A sandwich enzyme immunoassay for epidermal growth factor (EGF) has been developed which measures EGF concentrations in serum, urine, saliva, gastric and pancreatic juices without pretreatment. Sensitivity for human EGF is 500 fg/tube. Serum EGF concentration in normal males and females is 780 and 604 pg/ml, respectively. Urinary human EGF is 51.3 ng/mg creatinine for males, and 68.3 ng/mg creatinine for females. The difference is not significant, and no correlation between serum and urinary concentrations exists, but serum concentration changes with age. The highest concentration is seen up to 9 years of age, suggesting that EGF promotes cell proliferation during growth.

Biliary cystadenocarcinoma followed up as benign cystadenoma for 10 years

We describe a case of biliary cystadenocarcinoma that showed a longterm clinical course. A 69-year-old Japanese man was admitted to our hospital because of abdominal discomfort. The patient had been diagnosed with benign cystadenoma of the liver at another hospital in 1987 and had been followed up for 10 years. Abdominal ultrasonography (US) and computed tomography (CT) scan demonstrated a unilocular cystic lesion, which included multiple conspicuous papillary protrusions in the left hepatic lobe. Left lateral segmentectomy was performed, and intraoperative cholangiography revealed a communication between the cystic tumor and intrahepatic bile duct. The tumor contained clear mucinous fluid and enfolded multiple yellowish papillary projections on the cystic wall. Histological examination showed the tumor to be biliary cystadenocarcinoma. The patient is doing well 4 years after the operation.

Experimental and clinical studies on epidermal growth factor for gastric mucosal protection and healing of gastric ulcers

In experimental studies, 0.6 N HCl-induced gastric mucosal injury was significantly severe in submandibularec-tomized rats (SMR rats) than that in either SMR rats receiving exogenous mouse EGF (SMR + EGF rats) or controls. This was also true in gastric injury induced by 0.4 N HCl under pretreatment with indomethacin to reduce gastric mucosal prostaglandins (PGs). Somatostatin (SLI), PGE2, and PAS-stained mucus in the corpus were significantly reduced in SMR rats in comparison to SMR + EGF and control rats. In clinical studies, salivary EGF secretion was much higher in peptic ulcer patients than healthy controls. β-Urogastrone was effective in the treatment of gastric ulcers. On the basis of experimental studies, we conclude that the protective effect of EGF on the gastric mucosa is, in part, mediated indirectly by increases in SLI, PGE2, and mucus production. However, endogenous, as well as exogenous, EGF has an important direct, cytoprotective effect on the gastric mucosa. From the clinical studies, we also conclude that salivary EGF secretion in ulcer patients increases in a homeostatic response to the presence of an ulcer, facilitating ulcer healing. Furthermore, we believe that β-urogastrone, human EGF, might prove to be an effective drug in the clinical treatment of gastric ulcers.

Protection of gastric mucosa against ethanol-induced injury by intragastric bolus administration of epidermal growth factor combined with hydroxypropylcellulose

Orally administered epidermal growth factor (EGF) has been shown to protect the gastric mucosa against injury induced by noxious agents. However, EGF administered by intragastric bolus appears to have less effect on the gastric mucosa because of its rapid excretion from th gastric lumen. In this study, mouse EGF given to rats by gastric intubation was confirmed to remain in the stomach at significantly high concentrations when given in combination with hydroxypropylcellulose (HPC), an agent that retards drug release. The residual mouse EGF levels in the gastric luminal content and tissue 3 h after administration of 50

Effects of Betazole Hydrochloride and Cyclic AMP on the Pepsinogen Secretion by Rabbit Gastric Mucosa in Organ Culture

mUg/kg of EGF dissolved in 1 ml of 2% HPC were 30 and 60 times higher, respectively, than those obtained after EGF alone. Pretreatment with intragastric bolus administration of EGF and HPC at the same dose for 3 h attenuated significantly the development of gastric lesions induced by absolute ethanol compared to that with HPC alone, EGF alone, or saline (mean values of ulcer index: EGF + HPC, 14.3; HPC, 52.8; EGF, 50.7; and saline, 63.2 mm). There were no significant differences between the ulcer index in the HPC, EGF, and saline groups. The present study indicates that exogenous EGF given as an intragastric bolus protects the gastric mucosa against injury when combined with HPC, which can bind to EGF and prevent its rapid excretion from the gastric lumen.

Persistent reflux symptoms cause anxiety, depression, and mental health and sleep disorders in gastroesophageal reflux disease patients.

The effects of betazole hydrochloride, dibutyryl cyclic AMP (DB-cyclic AMP) and betazole hydrochloride plus aminophylline on pepsinogen secretion by rabbit gastric mucosa were studied in organ culture. Betazole hydrochloride alone did not stimulate pepsinogen secretion at the concentrations of 10(-8), 10(-6), 10(-5) and 10(-4) M. However, 10(-3) M DB-cyclic AMP produced a significant stimulation of pepsinogen secretion into the culture medium when compared with the control. In the presence of 3 x 10(-3) M aminophylline, betazole hydrochloride in the concentration of 10(-5) and 10(-4) M stimulated pepsinogen secretion into the culture medium, and the magnitude of this increase was 2.0- and 2.8-fold, respectively, compared with the control. Aminophylline alone could not change pepsinogen secretion into the culture medium. These results suggested that the pepsinogen secretion, stimulated by betazole hydrochloride, was mediated by cyclic AMP in the chief cells.

Coexpression of organic anion‐transporting polypeptides 1B3 and multidrug‐resistant proteins 2 increases the enhancement effect of gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid on hepatocellular carcinoma in magnetic resonance imaging

Some patients with gastroesophageal reflux disease experience persistent reflux symptoms despite proton pump inhibitor therapy. These symptoms reduce their health-related quality of life. Our aims were to evaluate the relationship between proton pump inhibitor efficacy and health-related quality of life and to evaluate predictive factors affecting treatment response in Japanese patients. Using the gastroesophageal reflux disease questionnaire, 145 gastroesophageal reflux disease patients undergoing proton pump inhibitor therapy were evaluated and classified as responders or partial-responders. Their health-related quality of life was then evaluated using the 8-item Short Form Health Survey, the Pittsburgh Sleep Quality Index, and the Hospital Anxiety and Depression Scale questionnaires. Sixty-nine patients (47.6%) were partial responders. These patients had significantly lower scores than responders in 5/8 subscales and in the mental health component summary of the 8-item Short Form Health Survey. Partial responders had significantly higher Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale scores, including anxiety and depression scores, than those of responders. Non-erosive reflux disease and double proton pump inhibitor doses were predictive factors of partial responders. Persistent reflux symptoms, despite proton pump inhibitor therapy, caused mental health disorders, sleep disorders, and psychological distress in Japanese gastroesophageal reflux disease patients.

A case of acute lymphatic leukemia showed severe hepatic disorder and pancytopenia as primary symptoms.

We aimed to elucidate the relationship between the contrast enhancement effect of gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid (Gd‐EOB‐DTPA) on magnetic resonance imaging (MRI) of hepatocellular carcinomas (HCC) and the expressions of hepatocyte transporters (i.e. organic anion‐transporting polypeptide [OATP]1B3, multidrug‐resistant protein [MRP]2 and MRP3) and to clarify the characteristics of HCC with an MRI high‐contrast enhancement effect.

A Case of Familial Adenomatous Polyposis Associated with Colon Cancer, Ureteral Cancer and Two Early Gastric Cancers

症例は21歳, 男性. 1995年5月, 感冒様症状が出現し, 近医を受診. 肝機能障害を指摘され治療を受けるも軽快せず, 当院を紹介された. 入院時血液生化学検査ではGOT 3, 569U/l, GPT 3, 262U/l, 総ビリルビン値3.5mg/dl, プロトロンビン時間活性 (PT) 37.2%と著明な肝機能障害を認め, また白血球数は500/mm3と著明な低下を示した. 骨髄像では細胞数は減少していたが, 腫瘍細胞は認めなかった. ステロイドパルス療法などの治療により, 自・他覚症状ともに改善し退院したが, 同年10月, 再び肝機能障害が出現し再入院した. 第2回入院時に行った肝生検組織像, および骨髄像で腫瘍細胞を認め, 骨髄染色および表面マーカーから急性リンパ性白血病 (ALL) と診断した. ALLに重症肝障害をきたした報告は, 現在までに本症例を含め4例みられるが, 他の3症例では重症肝障害発症早期に死亡しており, 長期間にわたり経過を観察し得たのは本例のみであった.

Effects of cyclic nucleotides, betazole hydrochloride and acetylcholine on pepsinogen secretion from isolated rabbit gastric mucosa

A rare case of Familial Adenomatous Polyposis (FAP), associated with colon cancer, ureteral cancer and two early gastric cancers, is reported. A 42‐year‐old male was admitted to our hospital for evaluation of bloody stools and macrohematuria. There were six FAP patients in his family line, spanning four generations, and five had developed colon cancers. A barium enema revealed diffuse and scattered polyposis throughout the colon and an apple core sign in the descending colon. Abdominal CT disclosed right hydronephrosis with a markedly dilated ureter. Surgery was undertaken and included total colectomy, mucosal proctectomy, ileoanal anastomosis and right nephrectomy with ureteral resection, under a diagnosis of colon cancer and complete right ureteral stenosis. The resected specimens revealed a colon cancer in the descending colon, 50×32×15 mm in size and a ureteral cancer in the lower part of the right ureter, 30×16×16 mm in size.