A nested case-control study of stomach cancer in relation to green tea consumption in Japan.

To evaluate whether green tea consumption provides protection against stomach cancer, the relative risks (RRs) were calculated in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 157 incident cases and 285 controls aged 40-79 years. Cox proportional hazards regression analysis was used to estimate the RRs for stomach cancer. It was found that green tea consumption had no protective effect against stomach cancer. After adjustment for age, smoking status, H. pylori infection, history of peptic ulcer, and family history of stomach cancer along with certain dietary elements, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.3 (95% confidence interval (CI): 0.6-2.8), 1.0 (95% CI: 0.5-1.9), 0.8 (95% CI: 0.4-1.6), and 1.2 (95% CI: 0.6-2.5), respectively (P for trend=0.899). We found no inverse association between green tea consumption and the risk of stomach cancer.

A prospective study of stomach cancer death in relation to green tea consumption in Japan.

To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based on 30 370 men and 42 481 women aged 40-79. After adjustment for age, smoking status, history of peptic ulcer, family history of stomach cancer along with certain dietary items, the risks associated with drinking one or two, three or four, five to nine, and 10 or more cups of green tea per day, relative to those of drinking less than one cup per day, were 1.6 (95% CI: 0.9-2.9), 1.1 (95% CI: 0.6-1.9), 1.0 (95% CI: 0.5-2.0), and 1.0 (95% CI: 0.5-2.0), respectively, in men (P for trend=0.669), and 1.1 (95% CI: 0.5-2.5), 1.0 (95% CI: 0.5-2.5), 0.8 (95% CI: 0.4-1.6), and 0.8 (95% CI: 0.3-2.1), respectively, in women (P for trend=0.488). We found no inverse association between green tea consumption and the risk of stomach cancer death.

Aureusidin synthase: a polyphenol oxidase homolog responsible for flower coloration.

Aurones are plant flavonoids that provide yellow color to the flowers of some popular ornamental plants, such as snapdragon and cosmos. In this study, we have identified an enzyme responsible for the synthesis of aurone from chalcones in the yellow snapdragon flower. The enzyme (aureusidin synthase) is a 39-kilodalton, copper-containing glycoprotein catalyzing the hydroxylation and/or oxidative cyclization of the precursor chalcones, 2',4',6',4-tetrahydroxychalcone and 2',4',6',3,4-pentahydroxychalcone. The complementary DNA encoding aureusidin synthase is expressed in the petals of aurone-containing varieties. DNA sequence analysis revealed that aureusidin synthase belongs to the plant polyphenol oxidase family, providing an unequivocal example of the function of the polyphenol oxidase homolog in plants, i.e., flower coloration.

Deep brain stimulation of subthalamic area for severe proximal tremor.

Proximal tremors are often refractory to nucleus ventrointermedius thalami thalamotomy. Subthalamotomy has been suggested to be effective for treatment of tremor, although this procedure is associated with considerable adverse effects, and has rarely been considered a suitable treatment modality. The authors demonstrate the efficacy and safety of subthalamic deep brain stimulation in two patients, one with a severe, refractory proximal essential tremor and one with tremor with dystonia.

Colony stimulating factor-inducing activity of hesperidin.

To evaluate immunomodulating activities of bioflavones, colony-stimulating factor (CSF)-inducing activity of two dihydroflavones, three flavones and three flavonols were tested. These samples were suspended in saline and injected intraperitoneally (i.p.) into mice at a dose of 1 mg 6 h before bleeding. All compounds carrying the glucosyl-rhamnose moiety showed potent activity. Among them, hesperidin exhibited the strongest activity. Serum CSF production in mice injected with 1 mg hesperidin reached a peak at 9 h later. The activity of hesperidin was dose-dependent at a range of 0.3 to 20 mg/mouse.

Dorsal compartment syndrome of the upper arm. A case report.

A rare case of posttraumatic dorsal compartment syndrome of the upper arm is reported. This case was diagnosed by measuring the intracompartmental pressure. The patient was administered local anesthesia and immediately underwent surgery. The result was successful.

Colony stimulating factor-inducing activity of isoflavone C-glucosides from the bark of Dalbergia monetaria.

To obtain immunomodulating substances from Amazonian medicinal plants, hot water extracts from 21 samples available commercially were tested in terms of mitogenic and colony-stimulating factor (CSF)-inducing activities. Among them, Dalbergia monetaria exhibited the highest CSF-inducing activity. Orobol 8-C-glucoside (OCG-8) and orobol 6-C-glucoside (OCG-6) were isolated from the bark of D. monetaria as major constituents. The CSF-inducing activity of OCG-8 was higher than that of OCG-6 and a dose-dependent manner at a range of 0.1-10 mg/mouse. Serum CSF production induced by an intraperitoneal (i.p.) injection with 1 mg OCG-8 reached a peak at 4-6 h later, suggesting that OCG-8 would act on hematopoietic system.

Photochemically induced endothelial injury in the mouse as a screening model for inhibitors of vascular intimal thickening.

We have established a mouse model of intimal thickening and assessed its suitability for experimental studies of intimal thickening. Neointimal formation was observed after endothelial injury by photochemical reaction between transluminal green light and systemically administered rose Bengal, which represents a nonmechanical approach to vessel wall denudation. Intimal thickening began 7 days after endothelial injury, reached a maximum after 21 days, and then remained unchanged for as long as 42 days. Furthermore, as a consequence of neointimal proliferation, the luminal area gradually decreased. The cells in the neointimal layer were identified as smooth muscle cells by immunohistochemical staining with an alpha-actin-specific antibody. Extracellular matrix deposition in the neointima was markedly increased beyond 14 days after injury. Smooth muscle cell proliferation, as measured by pulse labeling of 5-bromo-2'-deoxyuridine, was identified initially in the media 2 days after vessel wall denudation, with the proliferative activity's shifting almost exclusively to the neointima within 7 days. Endothelial regeneration, as indicated by Evans blue staining, was complete within 21 days after injury. To assess the suitability of this model for experimental studies on intimal thickening, the effect of tranilast, an antiallergy drug with a broad spectrum of pharmacological actions on intimal thickening, was investigated. Tranilast (100 mg x kg(-1) x d(-1) p.o.) significantly (P<0.05) reduced smooth muscle cell proliferation in the neointima and media 7 days after injury and neointimal formation 21 days after injury in treated mice compared with vehicle-treated mice. This simple experimental mouse model is suitable for studying factors promoting or inhibiting intimal thickening after endothelial injury and for developing therapeutic strategies against intimal thickening.

Modulation of eosinophil chemotactic activities to leukotriene B4 by n-3 polyunsaturated fatty acids.

Eosinophil accumulation induced by leukotriene B4 appears to be involved in the pathogenesis of allergic diseases. We evaluated the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on chemotaxis to leukotriene B4 in guinea pig peritoneal eosinophils. Guinea pigs that were sensitized to polymyxin B were administered an intraperitoneal injection of polymyxin B (1 mg/animal) alone or combined with DHA (15 or 50 mg/kg, i.p.), EPA (50 or 100 mg/kg, i.p.), or with linoleic acid (LA) (100 mg/kg, i.p.). Forty hours later, eosinophils were obtained from the intraperitoneal lavage fluid and purified. The chemotactic and chemokinetic responses of eosinophils to leukotriene B4 were measured using a 96-well microchemotaxis chamber. DHA significantly decreased the chemotactic and chemokinetic responses of eosinophils in a dose-dependent fashion. A higher dose of EPA also significantly inhibited both of those responses, whereas LA had no effect. Our results suggested a possible mechanism for the improvement of allergic diseases by dietary supplementation with n-3 PUFA.

Effects of indomethacin administration on bone turnover and bone mass in adjuvant-induced arthritis in rats.

We examined the bone turnover and bone mass in adjuvant-induced arthritis in rats and assessed the effects of indomethacin in this model. One hundred ten SD rats, 6 weeks of age, were assigned to 11 groups and injected with adjuvant or solvent in the right foot. Adjuvant-injected rats were orally administered indomethacin at doses of 0 (vehicle), 0.1 (low), 0.5 (medium), and 1.5 (high) mg/kg body weight from the start (day 0). Animals were sacrificed on days 0, 14 (acute phase), and 28 (chronic phase). In the arthritic-control group, serum osteocalcin level and bone mineral content of the fourth lumbar body (L4) and the femur were significantly reduced on day 14. Serum alkaline-phosphatase was increased on day 28. Trabecular bone volume of L4 was decreased on day 14, and the value was further decreased on day 28. Bone formation rate (BFR/BS) was significantly reduced on day 14, and then osteoclast number (Oc.N/BS) increased on day 28. Indomethacin treatment dose-dependently prevented increases in paw volume and osteoclast number. In the high dose group, these indices were maintained at the same level with those in the normal group. However, indomethacin treatments were not able to maintain the parameters of bone formation such as serum osteocalcin and BFR/BS values, and the trabecular bone mass decrease was only partially prevented. These data clearly indicated both reduced bone formation and increased bone resorption as the causes of bone loss in adjuvant-induced arthritis in rats. Increased bone resorption seemed to be due to the increased activity of prostaglandins, but bone formation defect would be related to other factors in this animal model.

Inhibitory effect of a novel orally active GP IIb/IIIa inhibitor, SC-54684A on intimal thickening in the guinea pig femoral artery.

The inhibitory effect of a novel orally active platelet membrane glycoprotein receptor complex IIb/IIIa (GP IIb/IIIa) inhibitor, SC-54684A is studied on intimal thickening in the guinea pig femoral artery. A segment of the femoral artery was occluded by a platelet-rich thrombus induced by photochemical reaction between systemically administered Rose Bengal and transluminal green light which causes endothelial injury followed by platelet adhesion and aggregation at the site of photochemical reaction. Three weeks after successful thrombolysis by tissue-type plasminogen activator, intimal thickening occurred at the irradiated site. SC-54684A (30 mg/kg), administered 2 h before photochemical reaction, significantly (P < 0.05) prolonged the time to occlusion of the femoral artery; in this respect aspirin (100 mg/kg) was ineffective. A combination of SC-54684A and recombinant tissue-type plasminogen activator (rt-PA) increased the frequency of reopening and significantly (P < 0.05) prolonged the duration of reflow compared with rt-PA alone. Further, SC-54684A administered orally twice a day for 3 weeks significantly (P < 0.05) inhibited intimal thickening but aspirin, administered orally once a day for 3 weeks, was ineffective. Scanning electron microscopy revealed extensive platelet adhesion and aggregation on the denuded vessel walls in the untreated group 24 h after successful thrombolysis. In separate experiments, SC-54684A markedly inhibited platelet aggregation ex-vivo. Inhibition of platelet adhesion and aggregation at the site of endothelial injury by SC-54684A (via GPIIb/IIIa inhibition) may account for its inhibitory effect on intimal thickening.

Inhibition of PDGF- and TGF-beta 1-induced collagen synthesis, migration and proliferation by tranilast in vascular smooth muscle cells from spontaneously hypertensive rats.

Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) proliferate faster and are more sensitive to transforming growth factor-beta 1 (TGF-beta 1) than those of normotensive Wistar-Kyoto rats. We studied the in vitro effects of tranilast, an anti-allergic drug, on the proliferation, migration and extracellular matrix synthesis in the SHR-VSMC. There were many inhibitory effects of tranilast (30-300 microM) on SHR-VSMC. One is the effect on the proliferation stimulated with fetal bovine serum (FBS), TGF-beta 1 and platelet-derived growth factor-BB (PDGF-BB). Another is the effect on the PDGF-BB-induced migration. Lastly, tranilast exhibited inhibitory effects on spontaneous collagen synthesis and TGF-beta 1-induced collagen and glycosaminoglycan synthesis. On the other hand, collagen induced the VSMC migration concentration-dependently. These results suggest that tranilast may prevent restenosis after percutaneous transluminal coronary angioplasty.

Iron and erythropoietin measurement in autologous blood donors with anemia: implications for management.

BACKGROUND: The importance of autologous blood donation for elective surgery is recognized, and the method is being used at many hospitals. Not all patients are able to deposit a sufficient amount of blood before surgery because they cannot recover rapidly enough from phlebotomy-induced anemia. The ability to donate sufficient blood for autologous use was studied in patients who are particularly susceptible to phlebotomy-induced anemia. STUDY DESIGN AND METHODS: Of 840 patients who donated blood for autologous use in elective surgery from November 1987 through May 1993, 20 with rheumatoid arthritis, 24 with iron deficiency anemia, and 37 aged 65 years and above with normocytic anemia were compared with 24 nonanemic elderly patients who donated a total of 1000 mL of blood for autologous use. Patients received iron sulfate orally and donated blood once a week until operation. RESULTS: The amount of blood collected before surgery per control patient was more than that in others. Consequently, there was a tendency to allogeneic blood transfusion in patients with rheumatoid arthritis or elderly patients. The ferritin levels in controls and in patients with iron deficiency anemia during the donation period were almost within the normal range in spite of iron supplementation, which implied a good utilization of iron sulfate for erythropoiesis. On the other hand, the rise in ferritin levels in the elderly and in patients with rheumatoid arthritis suggested inappropriate iron availability for erythropoiesis and resulted in an increase in iron storage. Since an adequate endogenous erythropoietin response to phlebotomy-induced anemia was not observed in these patients, impaired erythropoietin production was considered one of the reasons for anemia. CONCLUSION: Patients with iron deficiency anemia are able to continue donating blood for autologous use so long as they have sufficient iron supplementation. However, the elderly or those with rheumatoid arthritis occasionally fail to donate a sufficient volume of blood before surgery as a result of phlebotomy-induced anemia, which is caused in turn by impaired erythropoietin production.

Autologous blood donation elective surgery in children.

Studies were made on 59 children (cardiac 42, orthopaedic 13, miscellaneous 4) scheduled for autologous blood donation before elective surgery. The donor-patients' ages ranged from 3 to 15 years (mean 9.9 years) and their weights from 13 to 70 kg (mean 34 kg). All patients received 50-100 mg of oral iron sulphate per day. As a rule, about 10% of intravascular blood volume was drawn once a week. Before surgery, an average of 720 ml of autologous blood per patient was prepared. Two patients failed to donate autologous blood because of anxiety about the procedure; however, none of the donors was deferred due anaemia associated with the phlebotomy. Of the 53 patients undergoing surgery and participating in autologous predonation, 50 (94%) were able to avoid homologous blood transfusion. 600 ml of homologous blood were transfused to each of 2 orthopaedic patients and 400 ml to 1 cardiac patient. We conclude that a predeposit autologous transfusion programme is logistically possible in small children when the patients are cooperative.

An electrocochleographic study of acute low-tone sensorineural hearing loss.

Twenty-four patients with acute low-tone sensorineural hearing loss (ALHL) were examined using electrocochleography. The negative summating potential (SP) amplitude and the summating potential/action potential (AP) ratio were significantly greater in the ALHL patients than in normals. The SP/AP ratio was smaller in the ALHL patients than in patients with known Meniere's disease and moderate hearing loss, although the SP amplitude was somewhat greater in the former. An abnormal increase in the SP amplitude following click stimuli was found in 54% of the ALHL patients, while the SP/AP ratio was increased abnormally in 63% of these patients. These findings suggest that the pathophysiology of ALHL may be similar to that for endolymphatic hydrops.

Recombinant human erythropoietin for autologous blood donation: effects on perioperative red-blood-cell and serum erythropoietin production.

To speed collection of blood for autologous transfusion during elective surgery, patients may be given recombinant human erythropoietin (r-HuEPO). In a controlled trial, we evaluated the effects of r-HuEPO on perioperative red-blood-cell and serum erythropoietin (s-EPO) production in patients donating blood before elective orthopaedic surgery. Patients were assigned randomly to receive no r-HuEPO (12 patients), or 3000 U (4), 6000 U (5), or 9000 U (4) of r-HuEPO intravenously twice a week from the time of the first blood donation. All patients received iron sulphate. 1200 ml blood was collected from each patient in three weekly donations of 400 ml. The 3000, 6000, and 9000 U treatment groups produced 284, 350, and 383 ml, respectively, of red cells during donation, and the untreated controls produced 211 ml. s-EPO concentrations were within the normal range during donation. After surgery, s-EPO concentrations peaked on postoperative day 1 in untreated patients and on day 7 in treated patients; therefore, r-HuEPO may suppress endogenous erythropoietin secretion. Although administration of r-HuEPO increases production of red blood cells, the preoperative anaemia induced by repeated phlebotomy without r-HuEPO may accelerate the postoperative secretion of endogenous erythropoietin.

Identification and structural characterization of further DNA elements in the potato and pepper genomes homologous to the transposable element-like insertion Tst1.

The molecular cloning and nucleotide sequence of elements from potato and pepper that are related to the recently identified Tst1 element are described. Sequence analysis reveals considerable conservation of sequences internal to both the Tst1 element and two of the related elements identified here. In six potato clones analysed, the 11 bp inverted repeat first identified in the Tst1 element is conserved. Several of the elements are flanked by an 8 bp direct repeat. DNA fragments which were amplified from several pepper genomes by polymerase chain reaction (PCR) amplification using the inverted repeat as sequence primers also display considerable conservation of sequences internal to the Tst1 element. These data further support the possibility that Tst1 is a non-autonomous transposable element and that Tst1 might be the first example of a transposable element which occurs in several genera of solanaceous plants.

Chai-ling-tang (Japanese name: sairei-to) as an oral adjuvant.

Immunomodulating and anti-tumor activities of orally administered Chai-Ling-Tang (Japanese name: sairei-to, ST) were investigated. The oral administration of ST into mice augmented the antibody response to intraperitoneally administered 2, 4, 6-trinitrophenyl-haptenated sheep red blood cells (TNP-SRBC). Orally administered ST showed also an enhancing effect on the antibody response to TNP-SRBC administered by the oral route. In addition, orally administered ST markedly activated the peritoneal macrophages to enhanced phagocytic and lysosomal enzyme activities. A significant inhibition of tumor growth was observed in a syngeneic tumor-mouse system when ST was administered orally. These results suggest that ST has an efficiency as an oral adjuvant or an oral biological response modifier (BRM).

Pharmacokinetic analysis in intraperitoneal hyperthermic chemotherapy of far-advanced gastric cancer patients.

The pharmacokinetics of mitomycin C (MMC) has been evaluated in 10 far-advanced gastric cancer patients by means of an intraperitoneal hyperthermic perfusion (IPHP) using MMC to prevent and/or treat peritoneal dissemination. Further, misonidazole (MIS), which was used as a thermosensitizer, also was evaluated. The IPHP was performed for 120 min right after surgical procedure, using a closed-circuit with an inflow perfusate temperature from 46.3 approximately 47.5 degrees C and an outflow temperature of 44.0 approximately 46.0 degrees C. The MMC level in the perfusate was 10 micrograms/ml at the onset of IPHP and thereafter decreased to 1.7 +/- 0.4 micrograms/ml minutes later. The average AUC (area under the curve) in the perfusate was 3.3 micrograms/ml during the IPHP. The MMC level in the peripheral blood was 0.15 +/- 0.04 micrograms/ml 30 min after start of the IPHP and increased to 0.18 +/- 0.05 micrograms/ml at the end of IPHP. Additionally, the MIS level in the peripheral blood was 64.7 +/- 10.3 micrograms/ml 60 min after the IPHP, 60.6 +/- 9.2 micrograms/ml at 120 min, and then decreased to 32.8 +/- 10.3 micrograms/ml at 12 hours after IPHP. The AUC was calculated as being 975 micrograms.hr/ml. Again, the level in the portal vein blood was calculated from the peritoneal permeability and the peripheral blood level of the drug. From data, it was concluded that the perfusate and portal vein blood level of MMC, the peripheral blood level of MIS, as well as the perfusate temperature, are important in providing a favorable, safe, antitumoral treatment.