Micro-determination of cyclic AMP levels in human epidermis, dermis and hair follicles

In order to study the biological and possible pathological roles of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in the skin, it is mandatory to measure cyclic AMP in 50-100 mug of microdissected epidermis, dermis or appendages. In the present study, we offer a method of extracting cyclic AMP from less than 100 mug of tissue, removing contaminating nucleotides and scaling down Gilman's method to fit the analysis of small amounts of tissue. Cyclic AMP levels in the dermis, epidermis, and hair follicles (bulbs) were approximately 1, 2 and 3-5 pmols/mug dry weight tissue respectively. This procedure is applicable to the measurement of cyclic AMP levels in limited foci of healthy or diseased skin.     

A Case of Gastric Cancer Achieving a Complete Response by Chemotherapy

An 80-yr-old man with advanced gastric cancer was admitted onSeptember 10, 1982. He received no surgery owing to a moderateattack of bronchial asthma, hypertension and cardiac, pulmonaryand renal function disturbances. Chemotherapy was started afterdischarge. The treatment regimen was the oral administrationof 5-fluorouracil tablets at a dose of 200 mg a day, every day.Endoscopic examination 10 weeks after the initiation of chemotherapyrevealed complete regression of the tumor and the biopsy specimenrevealed no cancer cells. Since then, X-ray and endoscopic examinationhave been performed every two to three months. The patient isstill well without relapse of the disease.     

Ten Years' Experience With Intra-Aortic Infusion Chemotherapy for Gastrointestinal Malignant Tumors

Ten years' experience with intra-aortic infusion chemotherapyfor 114 patients with unresectable or recurrent gastrointestinalmalignant tumors is described. A marked response (1-B in Karnofsky'scriteria) was obtained in a type of simple peritoneal disseminationof stomach carcinoma and in a locally recurrent type of rectalcarcinoma. However, the overall response rate was low and theduration of response was generally short for gastrointestinalmalignant tumors. The rationale of chemotherapy by the intra-aorticroute is to enhance the antitumor response and to reduce drugtoxicity as compared with that by the intravenous route. Thedrug of choice is 5-fluorouracil (5-FU) in intraaortic continuousinfusion. As far as 5-FU is concerned, no toxic manifestationwas observed in most cases. However, the major complication.i.e. aortic perforation at the level of an indwelling cathetertip, which is attributed to the chemical action of 5-FU, occurredin two cases. Cancer chemotherapy is discussed on the basisof our experience with intra-aortic infusion treatment with5-FU. Our previous results suggest that the drug sensitivityof individual cancer tissues is the most important factor.     

山茶种子总皂苷碱水解产物的化学成分

目的研究山茶[Camellia sinensis(L) O.Kuntze]种子总皂苷碱水解产物的化学成分。方法采用反复制备型反相HPLC法分离纯化,通过理化常数测定和波谱分析鉴定其化学结构。结果从山茶种子总皂苷的碱水解产物中分离得到5个去酰基茶皂苷类化合物,即desacyl-assamsaponin A(1)、desacyl-assamsaponin D(2)、desacyl-assamsaponin E(3)、desacyl-assamsaponin F(4)、desacyl-theasaponin E(5)。结论对山茶种子总皂苷碱水解产物化学成分系统研究尚属首次,可为山茶皂苷类化合物生物活性的构效关系研究提供参考。     

High-dose mizoribine treatment for adolescents with systemic lupus erythematosus

BACKGROUND: In treating pediatric patients with systemic lupus erythematosus (SLE), it is necessary to quickly attain remission to avoid sequelae in various organs and to maintain it over a long period. However, to maintain remission, the prolonged use of immunosuppressants which have various adverse effects, is often necessary in addition to steroids, and complications due to such immunosuppressants pose very important problems. A regimen of mizoribin (MZR) at 150 mg/day divided into two or three doses has been recommended, but while this regimen has been safe, its efficacy has not been satisfactory. However, MZR produces effects dose-dependently, and the dose recommended to date may have been insufficient for the treatment of children with SLE. METHODS: The authors administered oral MZR at 300 mg/day in two divided doses, which is twice the conventional dose for adults, to five adolescents with SLE. Three of these five were markedly steroid-dependent patients and two had previously been treated with steroids only. Thereafter, the authors evaluated the safety and efficacy of the regimen by following the patients for at least 7 months after the beginning of treatment. RESULTS: Patients 1 and 2 had been treated with prednisolone (PSL) and cyclosporine (CyA), but as the duration of CyA administration became long, it was replaced with 300 mg MZR. This transition could be accomplished smoothly. Patient 3 showed repeated recurrence during the treatment with PSL and CyA or CPM, but the symptoms could be controlled by the addition of 300 mg MZR. In patients 4 and 5, the control of symptoms with PSL alone was judged to be difficult, and concomitant administration of MZR at 300 mg was started. This resulted in a decrease in the dose of PSL. The Cmax (C2) of MZR was 1.33 microg/mL or higher in all five patients, and the efficacy of the treatment was satisfactory. Concerning side-effects, hyperuricemia was noted in two patients, but it was resolved in one of them by reducing the dose of MZR and in the other spontaneously while the treatment was continued. Temporary exacerbation of hair loss was observed in two patients, but it disappeared in both of them after a few months. CONCLUSION: MZR could be administered at a high dose effectively and safely. However, monitoring of the serum uric acid level was necessary. High-dose MZR therapy showed an efficacy and safety that would warrant its application to steroid-dependent pediatric patients with SLE.     

Regional differences in microvascular response in rat intestine during acute elevation of portal pressure

The effect of acute elevation of portal pressure on the blood flow of rat intestinal microvessels was studied using a laser Doppler velocimeter and in vivo microscopy. The total intestinal blood flow decreased when portal pressure increased more than + 15 cmH₂O above the basal value. Blood flow in villus capillaries did not change at portal pressures of + 5 to + 15 cmH₂O, but did decrease at + 20 cmH₂O. Blood flow in muscle capillaries decreased at all steps of portal hypertension. Red blood cell velocity was decreased by portal hypertension in large venules, but not in small venules of the submucosa. Large venules, but not small venules, dilated in acute portal hypertension. Large arterioles in the submucosa constricted, while small arterioles dilated at portal pressures of + 10 to + 15 cmH₂O. In conclusion, the intestinal microvascular flow response differs according to the degree of portal hypertension and the location on the microvascular tree. Blood flow in villus capillaries and in small submucosal venules is maintained at a small degree of portal hypertension.     

Susceptibility of experimental autoimmune hepatitis in transgenic mice overexpressing the c-H-ras gene

Results from a recent study of ours have demonstrated the significant role of the wild-type ras gene in the development of hepatocellular carcinoma in rasH2 mice having prototype human c-H- ras genes. Chronic cell death and regeneration have been considered to work as co-carcinogens with wild-type ras gene overexpression in this model. To elucidate a role of gene overexpression in the occurrence of chronic inflammation, we tried to induce inflammation in the liver of rasH2 mice by immunizing them with the supernatant of a freshly prepared syngenic liver homogenate. Immunization resulted in a dense inflammatory infiltrate in the portal tract and focal necrosis with spots of fatty or foamy degeneration in the transgenic mouse liver; however, these observations were less frequently observed in non-transgenic mouse liver. Monocytes, granulocytes and plasma cell infiltration were observed in the livers of transgenic mice. An immunohistochemical study showed that CD3-positive lymphocytes also infiltrated the liver. The inflammatory infiltrate was still present in the transgenic liver 24 weeks after the last injection, but little infiltrate was observed at the same time in non-transgenic mice. No hepatic tumours could be produced over the 6 months duration of the study and the results are only preliminary. However, these results do suggest that overexpression of wild-type ras is partially responsible for the occurrence of autoimmune chronic hepatitis.