Argyrophilic nucleolar organizer regions in colorectal malignancy: application of typing by their density.

Colorectal neoplasms obtained at colonoscopy were examined by argyrophilic nucleolar organizer region (AgNOR) staining to evaluate the usefulness of AgNOR as a discriminant for malignancy. AgNOR dots were divided into two kinds: 'structures' (larger and less-densely stained) corresponding to the nucleolus, and 'units' (smaller and densely stained) presumed to be true AgNOR within the structure. The number of structures per nucleus did not differ between the adenoma and carcinoma groups, whereas the number of units per nucleus showed a significant difference. However there were several cases showing an overlap between the adenoma and carcinoma groups, leading to a difficulty in deciding whether any given case was benign or malignant. Three types of AgNOR patterns were categorized based on the ratio of units to structure. Type I was defined as the unit being indistinguishable from the structure, Type II as each structure having one to five units, and Type III as at least one structure having six or more units, irrespective of total number of units per nucleus. The colorectal lesions in which more than half of the neoplastic cells showed Type III coincided well with carcinomas histologically diagnosed, with the exception of adenomas with severe atypia. Labeling index of proliferating cell nuclear antigen (PCNA LI) differed between the adenoma and carcinoma groups with a considerable extent of overlap, and correlated to some extent with the AgNOR values. These results showed that the AgNOR staining was useful for determining malignancy and its usefulness appeared superior to PCNA LI.

Terahertz-rate optical pulse generation from a passively mode-locked semiconductor laser diode.

We report what is to our knowledge the first demonstration of terahertz-rate optical pulse generation by harmonic passive mode locking in a distributed-Bragg-reflector laser diode. Along with the fundamental repetition rate of 38.8 GHz, we observed 400-GHz, 800-GHz, and 1.54-THz harmonics, depending on the bias condition of gain section. The pulse envelope for 1.54-THz pulses was in good agreement with a calculation from the Fourier transformation of the optical spectrum, indicating that the output pulses are transform limited.

[Granisetron oral phase III clinical trial--study on the inhibitory effect of granisetron for nausea/vomiting induced by chemotherapy for tumors in the hematopoietic organs].

The efficacy and safety of oral granisetron against nausea and vomiting induced by chemotherapy for tumors in the hematopoietic organs were investigated. Depending on the day of anticancer drug administration, single administration or 2 to 6-day repeated administration of granisetron at 2 mg once daily was conducted. The clinical efficacy rate against nausea and vomiting was 91.6% on the first day of administration of anti-cancer drugs and 90% or over on and after the second day of administration. Compared with the status at the previous chemotherapy, a significant decrease in vomiting frequency was observed during the present trial. Adverse events which were suspected to be related to granisetron included 1 case of mild feeling of residual urine and another demonstrating very mild eosinophilia. From the above results, it was confirmed that granisetron was a safe and effective antiemetic against nausea and vomiting induced by anticancer drug administration.

Method of generating nearly transform-limited pulses from gain-switched distributed-feedback laser diodes and its application to soliton transmission.

A train of nearly transform-limited pulses are generated from a 1.55-microm distributed-feedback laser diode by using gain switching in a novel technique, which is a combination of a spectral window and temporal compression. By amplifying these pulses with erbium-doped fiber amplifiers, we demonstrate soliton transmission in a conventional single-mode fiber.

Hormonal regulation of plasminogen activator production by rat hepatocytes in primary culture.

Hormonal regulation in the production of a plasminogen activator (PA) was studied in rat hepatocytes in primary culture. Insulin and epidermal growth factor had no effect on the hepatic PA activity. However, glucagon and epinephrine augmented the activity, whereas dexamethasone suppressed it by lowering the production of hepatic PA rather than by inducing plasmin inhibitors or a plasminogen activator inhibitor (PAI). Dibutyryl cAMP, an analogue of cAMP, also augmented hepatic PA activity. The augmented activity level was lowered by either H-8, cycloheximide, or actinomycin D, suggesting that A-kinase and protein biosynthesis are closely associated with the augmentation. Glucocorticoid and hormones that act to raise the intracellular cAMP level may participate in hepatic PA production by the liver.

Ranitidine and sucralfate as maintenance therapy for gastric ulcer disease: endoscopic control and assessment of scarring.

The efficacy of ranitidine (150 mg nocte), and sucralfate (1 g tds) as maintenance therapy to prevent gastric ulcer relapse was evaluated in a 12 month trial in 363 patients. The relapse rates were 8.8% at three months, 14.7% at six months, 18.1% at nine months, and 21.0% at 12 months for the ranitidine group and 14.7%, 21.3%, 29.9%, and 30.2% respectively for the sucralfate group. At nine and 12 months the cumulative relapse rates for the ranitidine group were significantly lower than those for the sucralfate group (p less than 0.05). In both groups ulcers recurred mainly from red scars observed at the endoscopic scarring stage. This indicated the necessity of drug treatment up to the white scar stage. The results suggest that ranitidine is effective in preventing gastric ulcer relapse.

Studies on bilokinase, a biliary plasminogen activator: immunologic property and organ distribution.

The aim of the present study was to elucidate the immunologic difference between bilokinase, a plasminogen activator in bile, and urokinase, an urinary plasminogen activator, and to demonstrate the organ distribution of these antigens. Polyclonal antibodies against the highly purified activators (bovine-bilokinase, -urokinase and human urokinase) were raised in rabbits or guinea pigs. Immunologic precipitin reactions and quenching were found to occur only between the activators and their respective antisera. Histo-immunologic demonstration of the activators revealed that bilokinase-antigen was localized mainly in the hepatocytes as well as in the mucosa of the gall bladder, whereas urokinase-antigen was present in the epithelium of the urinary tubules. The liver may have a potential role in the hepatobiliary fibrinolytic system.

[Conditions of the primary culture for rat hepatocytes and plasminogen activator release].

The conditions of primary culture for rat hepatocytes was investigated on the releasing effect of Plasminogen Activator (PA). The culture method using Collagen Coated Dish (CCD-method) which is currently available and the ordinary culture method using Plastic Culture Dish (PCD-method) were employed for that purpose in a comparative way. The effect of the addition of some supplements, that is FN, Aprotinin, EGF were also investigated. The following results were obtained. The dissociated rat hepatocytes formed a monolayer with pavementlike morphology at 24-48 hours after seeding. No difference was observed in the morphology of hepatocytes during the culture period between the two methods, although CCD-method allowed 120 hours culture, whereas PCD-method allowed 72 hours. The PA activity was demonstrated on the hepatocytes by either culture method according to the fibrinolysis autography. The cultured hepatocytes released PA into the medium continuously as long as the viability and morphology of the cells were maintained in good state. The PA activity reached the maximum after 96 hours culture in CCD-method, whereas it reached the maximum after 48 hours in PCD-method. The addition of Aprotinin to the culture medium was not necessary for PA release in CCD-method in contrast to PCD-method. When EGF was discontinued in the culture medium, the release of PA was reduced in association with the occurring of morphological disintegration of hepatocytes.

Turnover of fibrinopeptide A (FPA) in rabbits.

FPA disappeared from the circulating blood along a double-exponential decay curve consisting of an initial phase (t 1/2 = 1.8 min) and a late phase (t 1/2 = 34.7 min). The rapid decrease in blood FPA was due to the large extravascular space, the size of which was estimated to be about 5 times larger than that of intravascular space. The actual amounts of 125I-FPA distributed to the organs and tissues were generally quite low. However, in the case of the urine, the injected amount of FPA was excreted at the rate of 50% per hour. Thus, the urinary FPA levels may reflect the occurrence of intravascular coagulation.

Clinical usefulness of ranitidine in giant gastric ulcer.

We define "giant" gastric ulcer as a chronic gastric ulcer, with a diameter greater than or equal to 3 cm. Treatment of inpatients with several conventional antiulcer agents resulted in significantly lower healing rates in giant gastric ulcer than in "large" (greater than 15 and less than 30 mm diameter) or "medium" (greater than 5 and less than or equal to 15 mm diameter) ulcers. In 48 patients with giant gastric ulcers treated with ranitidine, cumulative endoscopic healing rates were: 0% after 2 weeks, 16.7% after 4 weeks, 50.0% after 6 weeks, 77.1% after 8 weeks, 85.4% after 10 weeks, and 87.5% after 12 weeks of treatment. Corresponding healing rates were determined for the control group, which included patients treated with various conventional antiulcer agents. Comparison of these results revealed that from the fourth week of treatment onward, healing rates of the ranitidine group were significantly higher than those of the control group. There was little difference in the cumulative healing rates in the ranitidine group. From these results, ranitidine is considered to be useful in the treatment of giant gastric ulcer.

Purification and characterization of the biliary plasminogen activator bilokinase.

The aim of the present study is to elucidate the enzymological and chemical properties of the plasminogen activator in bile, bilokinase. A bilokinase preparation was obtained from 94.2 liters of bovine gall bladder bile through seven purification steps, two of which employed a precipitation method in which ammonium sulfate and acetone were used sequentially. Twenty mg of bilokinase preparation with a specific activity of 5,900 IU/mg were obtained, for a 9% yield with 6,556-fold purification. This preparation revealed a single band upon disc electrophoresis. The bilokinase was a 3.32 S protein and its molecular weight was found to be 57,000. Isoelectric focusing showed that the bilokinase was separable into 5 fractions having different isoelectric points ranging from pH 7.4 to 9.0 The properties of the individual fractions have not yet been determined. The enzymatic activity of bilokinase was recognized to be heat-labile and to be stable at pH 4.0. The activation of plasminogen by bilokinase took place most effectively at pH 7.8 in a manner similar to that of urokinase. In its hydrolysis of both N alpha-acetylglycyl-L-lysine-methyl ester-acetate and H-D-Glu-Gly-Arg-pNA (S-2227), bilokinase showed similar Km values to those of urokinase; however, they were quite distinct from those of plasmin. It was concluded therefore that bilokinase is a plasminogen activator with enzymatic properties which are quite similar to those of the urinary plasminogen activator urokinase. The origin of bilokinase and its relation to liver function are now under investigation.

Ranitidine: a pilot study in Japan.

Twenty-four patients with gastric ulcer and 18 with duodenal ulcer diagnosed by endoscopy were treated with ranitidine, 300 mg day-1, for 8 consecutive weeks, or until the ulcer was found endoscopically healed. Of the 24 with gastric ulcer, 50% were healed within 4 weeks, and 83% within 8 weeks. Of 18 cases with duodenal ulcer, 50% were healed within 2 weeks and 94% within 4 weeks. Therapeutic effect of ranitidine was statistically significant compared with placebo. Side effects due to ranitidine administration were few and consisted of a rash in one case and slight increase of transaminase in a few patients.

Stomach ulcer and lysosomal cathepsin.

Gastric ulcers were induced in rats by i.m. injections of vitamin A, and i.p. injection of histamine, or injections of both vitamin A and histamine. The incidence of ulcer formation was highest in the vitamin A-histamine group. However, ulcer formation also occurred after the administration of vitamin A alone as a lysosomal labilizer. Furthermore, the vitamin A-histamine group showed a remarkably elevated cathepsin activity in the tissue of gastric wall. In the experiments of ulcer formation by vitamin A injections, the specific activity and the enzyme release of cathepsin were elevated already in the early stage after vitamin A administration. Consequently, cathepsin activity in stomach juice was remarkably elevated in the stage of the ulcer formation. In the clinic, the cathepsin activity in the mucous membrane of human gastric wall was remarkably high in the antrum and the angulus of the stomach, in which ulcer formation tends to occur most frequently. In view of these results, cathepsin in the stomach seems to play an important role in the formation of gastric ulcers.