Isolation of (+)-catechin and (-)-epicatechin from Actinidia arguta as bone marrow cell proliferation promoting compounds

The MeOH extract of stems of Actinidia arguta promoted proliferation of cultured bone marrow cells and stimulated formation of myeloid colonies from bone marrow cells. (+)-Catechin ( 1) and (-)-epicatechin ( 2) were isolated as active compounds from the MeOH extract. Compounds 1 and 2 stimulated the cell proliferation in a concentration-dependent manner in the range of 1 to 100 mg/mL. Compounds 1 and 2 also stimulated formation of myeloid colonies and enhanced the effect of interleukin-3 (IL-3) to increase the number of colony forming-units in culture (CFU-c). In an ex vivo experiment using a model mouse of decreasing bone marrow functions, orally administrated 1 (100 mg/kg/day) stimulated IL-3-induced CFU-c formation of the bone marrow cells.     

In Vitro System to Evaluate Oral Absorption of Poorly Water-Soluble Drugs: Simultaneous Analysis on Dissolution and Permeation of Drugs

Purpose. The aim of the present work was to develop a new in vitro system to evaluate oral absorption of poorly water-soluble drugs by utilizing Caco-2 monolayers. Methods. Caco-2 monolayer was mounted between side-by-side chambers, which enabled the simultaneous assay of dissolution and permeation of drugs (dissolution/permeation system; D/P system). Apical and basal sides of the chamber were filled with buffer solutions. Drugs were applied to the apical side as powder, suspension, or solution, and then, the permeated amounts into the basal side were monitored for 2 h. At the same time, dissolved amounts of drugs at the apical side were detected. The amount of drug applied to the D/P system was based on its in vivo clinical dose. Results. Sodium taurocholate (5 mM, apical side) and bovine serum albumin (4.5% w/v, basal side) increased the permeated amount of poorly water-soluble drugs. Both additives were considered to be effective at mimicking in vivo conditions of intestinal drug absorption. From the correlation between the permeated amount of 13 drugs (% dose/2 h) in the D/P system and their percentage dose absorbed in humans in vivo, this system was found to be useful in evaluating oral absorption of poorly water-soluble drugs. Conclusions. With attempts made to mimic the physiologic conditions of the human GI tract, in vivo oral absorption of drugs was quantitatively assessed in the D/P system in vitro. This system is quite useful to predict the oral absorption of poorly water-soluble drugs after administration as solid dosage forms.     

Histological classification of invasive ductal carcinoma and the biological parameters in breast cancer

BACKGROUND: The histological classification of invasive ductal carcinoma proposed by the Japanese Breast Cancer Society is based on the appearance of breast cancer invasion. However, few studies have been done to clarify the relationship between the histological classification and other parameters that represent the biological characteristics of individual breast cancer cells. MATERIALS AND METHODS: We analyzed 1,025 invasive ductal carcinomas, consisting of 424 papillotubular, 330 solid-tubular and 271 scirrhous cases, with regard to the status of estrogen receptor (ER), progesterone receptor (PgR), DNA ploidy, epidermal growth factor receptor (EGFR) and p53 protein. RESULTS: Absence of ER and PgR, aneuploidy, EGFR positivity and p53 protein positivity were all observed significantly more frequently in solid-tubular tumors than in the other two types. In addition, the number of abnormal features with regard to these 5 biological parameters was also significantly higher in solid-tubular tumors than in the other two types. CONCLUSION: Abnormalities in the biological parameters listed above were frequently found in the solid-tubular type of invasive ductal carcinoma.     

Mirimostim (macrophage colony-stimulating factor; M-CSF) improves chemotherapy-induced impaired natural killer cell activity,Th1/Th2 balance,and granulocyte function

The purpose of this study was to clarify the effects of mirimostim (macrophage colony-stimulating factor; M-CSF) on immunological functions after chemotherapy. The percentage of natural killer (NK) cells in peripheral blood mononuclear cells (PBMCs), NK cell activity, T-helper cell 1/T-helper cell 2 (Th1/Th2) ratio, and superoxide anion production by granulocytes (granulocyte function) were measured as immunological parameters before and after chemotherapy in 44 patients with primary ovarian cancer who received at least three consecutive courses of postoperative chemotherapy. Patients were observed during the first course of chemotherapy, and 39 patients who presented grade III or IV neutropenia were entered into this study and randomly allocated to an M-CSF-administered group (group 1; 19 patients) and a non-M-CSF-administered group (group 2; 20 patients) for the second course. For the third course, a crossover trial was conducted. In the observation period, chemotherapy significantly impaired the immunological parameters. In particular, those parameters were significantly decreased at day 14 compared to the level before chemotherapy. The values of the parameters of group 1 were significantly higher than those of group 2. In the course of chemotherapy during which M-CSF was administered, 19 of the 39 patients presented grade IV neutropenia, and received granulocyte colony-stimulating factor (G-CSF) between days 7 and 14. We compared the changes of those immunological parameters in the M-CSF alone group and the M-CSF+G-CSF group, and found that the concomitant use of G-CSF did not further improve the parameters. These results indicate that chemotherapy markedly impaired the immunological functions, and that the administration of M-CSF significantly improved the impaired immunological functions.     

Biweekly administration regimen of docetaxel combined with CPT-11 in patients with inoperable or recurrent gastric cancer

Background. Both docetaxel (TXT) and irinotecan (CPT-11) are active chemotherapeutic agents for gastric cancer. We designed a biweekly administration regimen of TXT combined with CPT-11 for 4 weeks as one cycle in patients with inoperable or recurrent gastric cancer, and conducted a dose-escalation study. Methods. Patients with histologically confirmed gastric cancer were treated with the regimen. The dosage levels of TXT and CPT-11 were as follows: level 1, 30mg/m² and 50mg/m²; level 2, 35 and 50mg/m²; level 3, 40 and 50mg/m²; level 4, 40 and 60mg/m²; and level 5, 50 and 60mg/m². The dose escalation was based on the dose-limiting toxicity (DLT) observed during the first cycle. Results. Grade 4 neutropenia was observed at level 3, but no other DLT was observed at less than level 4 during the first cycle. However, three patients at level 3 could not continue treatment without a decrease in the dosage after the second cycle. Based on these results, level 2 was considered to be the clinically recommended dosages. Conclusion. Biweekly TXT and CPT-11 was well tolerated. The recommended dosages of TXT and CPT-11 for a phase II trial are 35mg/m² and 50mg/m², respectively.     

Topographical Electrogastrograms After Radical Esophagectomy with Colonic Replacement

Purpose. To characterize the functional substitution of colon for the esophagus, we compared the electrogastrogram (EGG) maps and spectral frequencies and power of preoperative controls with patients who had undergone colonic replacement.Methods. Monopolar EGGs were recorded and spectrally analyzed at 27 locations on the thoracoabdominal surface. The spectral powers of five frequency groups were converted into EGG maps.Results. In contrast to the epigastric concentrations of maximal power foci in a preoperative 3-cpm (cycles per minute) group, those of the colon replacement subjects seemed not to be concentrated in the epigastric region. Power in the 6-cpm colon replacement group were significantly greater and those in the 3-cpm colon replacement group were significantly less than those in the preoperative controls. Spectral frequencies in the 1- and 3-cpm colon replacement groups were significantly higher than those in the preoperative controls.Conclusions. The colonic and gastric EGG activities had 3-cpm, and probably 6-cpm in common. However, the colonic EGG activities were significantly different from the gastric EGG activities in frequency in the 3-cpm group, and in amplitude in both the 3- and 6-cpm groups. Thus, the replaced colon seems to preserve the original colonic EGG activity.     

Peutz-Jeghers syndrome in children: high recurrence rate in short-term follow-up

We have managed four cases of Peutz-Jeghers syndrome (PJS) in children. Fathers of three of these patients had PJS. There was also a family history of cancer in three cases, with pancreatic cancer in a father, colonic and laryngeal cancers in a grandfather, and hepatic and gastric cancers in a grandmother. It is presumed that in each of the cases, the largest polyp was responsible for initial symptoms. Preoperative examination revealed additional small polyps in the whole alimentary tract except for the oesophagus. Patients underwent laparotomy to remove the largest polyps and subsequent intraoperative endoscopic polypectomy for other small polyps, to minimize intestinal resection. Follow-up gastrointestinal examinations, including upper gastrointestinal series, small intestinal contrast study, and barium enema, were repeated about once a year. Three of four cases showed recurrent small intestinal polyps, and one required a second laparotomy because of recurrent abdominal pain. In conclusion, patients with PJS occurring in childhood have a strong hereditary family history of cancer and a high incidence of recurrence. Careful follow-up examination is mandatory for the gastrointestinal tract, as well as other solid organs that are susceptible to malignant change, throughout a patient's life.     

Diagnostic laparoscopy in infertility: a retrospective study

STUDY OBJECTIVE: To evaluate the role of laparoscopy in the diagnosis and therapy of infertility. DESIGN: Retrospective study. SETTING: Academically affiliated reproductive endocrinology practice. PATIENTS: One hundred seventy patients. INTERVENTION: Diagnostic/therapeutic laparoscopy. MEASUREMENTS AND MAIN RESULTS: One hundred seventy infertile patients underwent diagnostic laparoscopy between 1996 and 2000 in our clinic, and 109 of them were seen at follow-up more than 1 year after laparoscopy. Of the 109 patients, 77 (70.6%) were treated with assisted reproductive technology, such as in vitro fertilization-embryo transfer, and 32 (29.4%) were treated with conventional procedures. Of the 109 patients, 68 (62.4%), including 39 (50.6%) of the 77 treated with assisted reproductive technology and 29 (90.6%) of the 32 treated with conventional procedures, became pregnant. Of the 68 patients who became pregnant, 49 (72.1%) of them conceived within 1 year after laparoscopy. CONCLUSION: Laparoscopy is an important procedure in the treatment of infertility.     

Successful treatment of a<Emphasis Type="Italic">Salmonella</Emphasis> aortic arch aneurysm

A 52-year-old man hospitalized for hoarseness and chest pain was found in chest computed tomography to have an impending aortic arch aneurysm rupture. Laboratory studies showed the presence of severe inflammation. Based on a clinical diagnosis of infected aortic arch aneurysm, we conducted total arch replacement.Salmonella was identified in the aneurismal wall and antibiotics were administered longterm. The postoperative course was uneventful. The patient was discharged on postoperative day 48. He has remained afebrile and asymptomatic in the 10 months since surgery but continues to take 300 mg/d of oral levofloxacin.