We studied alteration of the level of asparagine synthetase during the cell cycle of mouse fetal fibroblast BALB3T3 cells. The cells were synchronized to the G0 phase by culturing for 2 days in a medium containing a low concentration of fetal bovine serum (FBS), and then stimulated by FBS to progress to the S phase. After various intervals the enzyme activity and DNA synthesis were assayed. Specific activity of the enzyme increased 6 hr after the stimulation, i.e. 4 hr before the initiation of DNA synthesis. The content of the enzyme in the cells was also increased 4 hr after the stimulation and thereafter increased gradually. Cytosine arabinoside (Cytarabine), an inhibitor of DNA synthesis, did not affect the increase in the specific activity of the enzyme. These phenomena demonstrate that the induction of asparagine synthetase occurs in the G1 phase. We also studied effects of epidermal growth factor, of fibroblast growth factor, and of insulin on induction of the enzyme when each factor was administered to quiescent cells. Insulin, a progression factor, most potently induced the enzyme after 20 hr of incubation to a degree similar to that by FBS, although insulin elicited low DNA synthesis. It seems likely that DNA synthesis starts after the growth-signals through the G1 phase joined the event to induce asparagine synthetase or to enhance the production of asparagine.

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Anemia of premature infants in the early stage is well recognized, but its exact etiology is not well understood. One purpose of this study was investigation of relations between anemia in the early stage of premature infants and the significance of erythropoietin (Epo) . We first examined serum Epo levels in 42 full term infants and 28 premature infants with regard to hemoglobin (Hb) and hematocrit (Ht) at the 5th day of life. Specimens were obtained from healthy full term neonates and premature infants with no clinical abnormalities except low birth weight. Epo was measured by utilizing radioimmunoassay. Hb concentrations in full term infants were significantly higher than those in premature infants (P<0.05) . The tendency of Ht was similar. The Epo level of 9.83±3.14mU/ml in full term infants was not significantly lower than the level of 10.02±3.48mU/ml in premature infants. We then investigated whether or not we could forecast the early anemia of premature infants on the basis of Epo levels in some earlier stage. Serum Epo levels were measured in two groups of premature infants in the first week of life. In 17 infants, Hb concentrations fell below 10g/dl within 12 weeks of post neonatal life (anemic group) . In another group of 21 infants, Hb concentrations did not fall below 10g/dl (non-anemic group) . The Epo level was 11.37±4.92mU/ml in the anemic group, which was not significantly different from the level of 9.17±3.10mU/ml in the non-anemic group. No individual Epo level in any premature infant correlated with Hb concentration. W e concluded that there is no relation between Epo and birth weight or gestational age.

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Murakami's histological classification of ulcers of the digestive tract defines deep erosion as Ul- I and shallow erosion as Ul-0. Ul-0 was further subdivided into Ul-0¹, Ul-0², Ul-0³ and Ul-0⁴ according to the healing tendency. Ul-0^1-2 is the acute stage (active period) and Ul-0^3-4 is the healing stage (cicatricial period) . This erosion may be either benign or malignant, as observed in type II c of early gastric cancer and type IIa + IIc (IIc + IIa) . Such erosion of the gastric mucosa becomes important, because Ul-0 and Ul-I, including cancerous erosion, do not merely develop at the gastric mucosa with no other changes, but can also be detected in gastric mucosa where the changes of chronic gastritis are most often present. It is difficult to differentiate Ul-0 from Ul-I macroscopically, and precise macroscopic differentiation of smaller benign and malignant erosions is even more difficult. There are no methods, at present for such differentiation other than by microscopy. A clue to diagnosis by endoscopy that leads to microscopic diagnosis should be established.

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Lignin is a heterogenous natural plant substance composed of phenylpropenoid. We previously reported that lignified materials displayed diverse biological action such as stimulation of macrophage, antimicrobial, antiviral and antitumor activity. Here, we report that both lignin and synthetic dehydrogenation polymer of phenylpropenoids (so-called synthetic lignin) significantly induce tumor necrosis factor (TNF) production by the mouse macrophagelike cell line, J774.1, and by mouse residual peritoneal macrophages. The amount of TNF was measured by ELISA, using a specific monoclonal antibody against mouse TNF. The dehydrogenation polymer of calfeic acid (DHP-CA), among the synthetic lignins, most strongly induced TNF production. Recently, TNF has been revealed to have diverse biological activities in addition to antitumor activity. The results of our study suggest that part of the diverse biological action stimulated by lignin is due to the biological activity of TNF. The expression of TNF mRNA was also studied to investigate the mechanism of TNF induction by lignin. Northern blot hybridization was performed with total RNA obtained from the J774.1 cells and from mouse residual peritoneal macrophages after induction by treatment with DHP-CA. Bacterial lipopolysaccharides (LPS), one of the most potent inducers of TNF production by monocytes/macrophages, is well chararterized by its mechanism and induces TNF mRNA mainly at the level of transcription. We conclude, from the fact of Northern blot analysis that DHPCA did not show induction of TNF mRNA, that DHP-CA acts mainly at the level of translation, or posttranslational processing.

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We studied misidentification (Personenverkennung) which has been elucidated during daily clinical activities. The relevant symptoms centering on the core experience of the existence of a double, replacement or twin are extremely diversified, and this condition has been interpreted in various ways differing as to whether it is a psychogenic disease only, or is seen also in physical illness. Among the various terms applied internally, we have advocated the position that at the base of this experience is a warping or frustration in the experience of recognition or mistaken recognition.

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Five hundred and twelve patients with single colorectal carcinoma were administered during the 11 years between 1981 and 1991. The male to female ratio was 1.5: 1 and the average age of the patients was 64.0 years. Of 512 patients, 329 had carcinoma of the colon and 183 had carcinoma of the rectum. Pathologically, the non-infiltrated type of carcinoma affected 72.5 % and well to moderately differentiated adenocarcinoma affected 87.3 %. The curative resection rate was 70.9 % of colon carcinoma and 84.7 % of rectal carcinoma. The 5-year cumulative survival rate was 79.3 % of patients with curative resection. Lymph node metastasis increased with depth of invasion into the wall. The incidence of lymphatic invasion was high when invasion was over the pm-layer. The incidence of vessel invasion was high for invasion over the s⋅a₂-layer. Classification of the pathological stage was parallel to the prognosis of the patients with colorectal carcinoma.

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We studied 31 patients who had sarcoidosis but no treatment or any other respiratory disease, to determine relations among their pulmonary functions, especially small airway functions by Flow-Volume curves, radiographic stage, and clinical symtoms. Ventilatory functions were within normal limits, except in 3 cases, whereas small airway dysfunction (SAD), represented by any abnormality of %V₅₀, %V₂₅. %V₅₀/V₂₅, was detected in 15 cases. The mean values and prevalence of impairment in %V₅₀, %V₂₅, %V₅₀/V₂₅ were not affected by the radiographic stage or smoking, but the mean value of %DLco was significantly decreased in Stages II -III (n=9) compared to Stages 0- I (n=21) . The mean value of %V₂₅ was significantly decreased in the group with respiratory symptoms (n=7) compared to the asymptomatic group (n=14), and 6 patients of the group with respiratory symptoms revealed SAD by some abnormality of %V₅₀, %V₂₅, %V₅₀/V₂₅. For other pulmonary function data, there was no significant difference between the two groups. The results suggest that SAD in patients with sarcoidosis is connected with the appearance of respiratory symptoms.

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At our institution, preoperative laparoscopy has been used to assess advanced gastric cancer by judging the P or S factor. This is difficult to do with conventional imaging. In the present case, advanced gastric cancer of peritoneal metastasis was strongly suspected, and preoperative laparoscopy was effective in determining the suitability of the patient for surgery. The patient was a 45-year-old woman who was admitted because of lower abdominal pain and difficulty with defecation. Advanced gastric cancer, such as submucosal tumor, bilateral Kruckenberg's tumors, or Schnizler's metastasis, was diagnosed after admission. Total gastrectomy, abdominoperineal excision of the rectum, hysterectomy, and bilateral oophorectomy were performed after localized peritoneal metastasis was diagnosed by preoperative laparoscopy.

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Effects of phenobarbital (PB), valproic acid (VPA) or electroconvulsive seizure (ECS) on brain growth were studied in young Sprague-Dawley rats. To eliminate nutritional factors, 4-day-old rats were implanted with intragastric cannulas, through which they received a milk formula for 8 days. The rats were divided into a PB-treated group, a VPA-treated group, an ECS group, and 3 control groups. The PB and VPA groups received daily subcutaneous injections of phenobarbital (60 mg/kg/day) and valproic acid (200 mg/kg/day), respectively, for 6 days. The ECS group received two supramaximal ECS per day for 6 days. At the age of 11 days, the intragastric cannulas were cut and closed. Thereafter, the rats were reared by the dam from 11 to 21 days. There was no differences in body weights between controls and experimental groups during the experimental period. In the PB group, the brain weights (cerebrum, cerebellum) and cerebellar contents (DNA, RNA, protein) were significantly less than those of the control group. In the VPA group, the brain weights (cerebrum, cerebellum, brain stem) and cerebellar contents of DNA, RNA, were also significantly lower. In the ECS group, the cerebellar chemical contents were not significantly different from those in their control groups. Our data indicate that administration of anticonvulsants (PB, VPA) during early life might have adverse consequences on later postnatal brain development.

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We studied correlation between the menstrual cycle and airway hyperreactivity of 8 menstruation related asthmatics (MRA), 15 non menstruation related asthmatics (non MRA) and 9 normal subjects. We measured peak flow rates during menstrual cycle. Next, we measured serum hormones (aldosterone, progesterone, estradiol and cortisol) by the RIA method, and airway hyperreactivity to methacholine by the Astograph method, in the menstrual period and mid cycle period. Depression of peak flow rates occurred before and during menstruation in MRA, and minimum dose theshold was reduced during the menstrual period in MRA and non MRA. It is assumed that airway hyperreactivity rises during the menstrual period in menstruated asthmatics. Aldosterone increased in MRA and non MRA during the menstrual period, so airway hyperreactivity seems to be accompanied by fluid retention. The cortisol-estradiol ratio (C/E₂ratio) decreased in MRA and the progesteroneestradiol ratio (P/E₂ratio) increased in non MRA, during the menstrual cycle. W e suggest that hormonal unbalance causes MRA.

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We reported the first case of interstitial pneumonitis in a patient with rheumatoid arthritis treated with bucillamine in 1989. Since then, thirteen cases of bucillamine-induced pneumonitis have been reported. Here, we report the second case in our department. From analysis of these cases, we propose the following patient background as risk factors for bucillamine-induced pneumonitis,
Risk fartors of lung injury
1. Old age. Older patient with RA.
2. Patient who has suffered from RA for a long time.
3. Serum rheumatoid factor is highly positive. High RA activity, e.g. high RF titer.
4. Slight manifestation of lung fibrosis before the abrupt change. Pre-existing pulmonary injury of RA.
5. Exellent effect of bucillamine on rheumatoid disease activity in most cases. Good response to the drug. High responder to the drug, in general.
6. HLA typing, e.g. DR2, DR4 positive.
7. DLST or patch test with bucillamine is positive.

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The patient was a 36 year-old male. Hepatosplenomegaly appeared at 6 months and systemic lymph node swelling, anemia, leukopenia and thrombocytopenia appeared at 18 months. At 3 years, hemorrhagic spots appeared. The Letterer-Siwe disease was diagnosed from a lymph node biopsy. Remission was achieved by administration of corticosteroids and blood transfusion, and the clinical course of the patient was observed for 33 years until he died of liver cirrhosis caused by post-transfusion hepatitis. The marked proliferation of atypical histocytes in the lymph nodes, seen histologically at 3 years, was alleviated at 16 years, and disappeared after 29 years of age. Letterer-Siwe disease is usually progressive and has a poor prognosis, but in this case, the disease gradually remitted as the patient grew older. Considering the clinical course of this patient, it appears possible that Letterer-Siwe disease may heal and show a good prognosis once it has gone into remission.

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Subject is a 34-year-old male patient with the chief complaint of hematemesis. After repeated hematemesis on several occasions, patient was examined by a neighborhood physician and hemorrhage from a laceration at the esophagogastric junction and from a gastric ulcer was detected by endoscopy of the upper digestive tract, whereupon the patient was transferred to our department. At our department, emergency endoscopy was performed on this patient and diagnosed a Mallory-Weiss syndrome due to a hemorrhagic gastric ulcer. Clip hemostasis was performed on the hemorrhage form two pathologic sites. Thereafter the clinical course of the patient was favorable. Clip hemostasis for Mallory-Weiss syndrome is considered to be an effective method, as it does not cause secondary invasion, and repair effects on the wound can be expected. We discuss this case with a brief review of the literature.

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