Hypervalent iodine(III)-induced intramolecular cyclization of alpha-(aryl)alkyl-beta-dicarbonyl compounds: a convenient synthesis of benzannulated and spirobenzannulated compounds.

A novel hypervalent iodine(III)-induced direct intramolecular cyclization of alpha-(aryl)alkyl-beta-dicarbonyl compounds has been described. Both meta- and para-substituted phenol ether derivatives containing acyclic or cyclic 1,3-dicarbonyl moieties at the side chain undergo this reaction in a facile manner. The reactions afford benzannulated and spirobenzannulated compounds that are of biological importance. The reaction is found to be general, mild, and high yielding. The mechanism of the reaction has been shown to involve a cation radical intermediate.

[Differences between gynecological cancer patients taken care for at home and those taken care for at the hospital].

Thirty-five patients with end-stage gynecological cancer, twelve taken care for at home care and 23 taken care for at our hospital, were compared. The life span after recurrence was significantly (p < 0.05) longer in the group taken care for at home. The number of persons living with the patient was also significantly (p < 0.01) larger in the group taken care for at home. Moreover, the hospitalization in the end stage of the disease was significantly (p < 0.01) shorter in the group taken care for at home. The average hospitalization in the end was for 6.5 days. Four patients died at their home. Average period the 12 patients stayed at home was 52.7 days. Following matters are important in order to provide home care. 1. We must know the biological characteristics of the cancer. 2. It is important that it does not lose the timing to which shift to the home care, keeping good doctor-patient relationship. 3. Limit of the therapy against cancer and importance of treatment at home should be carefully and clearly explained to the patient.

[Development of intramolecular oxidative phenolic coupling reactions using hypervalent iodine (III) reagents and their application to the synthesis of Amaryllidaceae alkaloids].

Hypervalent iodine (III) reagents nowadays are used extensively in the field of organic chemistry. Especially, phenyliodine (III) diacetate (PIDA) or phenyliodine (III) bis(trifluoroacetate) (PIFA) have received much attention because of their reactivities similar to heavy metal reagents or anodic oxidation, low toxicity, ready availability and easy handling. In the continuous study of our oxidative phenolic coupling reactions using a hypervalent iodine (III) reagents, a versatile synthetic procedure for the galanthamine-type Amaryllidaceae alkaloids was accomplished. The first total synthesis of (+/-)-sanguinine and the total syntheses of (+/-)-galanthamine, (+/-)-narwedine, (+/-)-lycoramine, and (+/-)-norgalanthamine were also successfully carried out.

[Development of novel oxidation reactions using hypervalent iodine reagents and their application to total synthesis of biologically active natural products].

Recently, hypervalent Iodine (III) reagents have been used extensively in organic synthesis. In particular, phenyliodine (III) diacetate (PIDA) and phenyliodine (III) bis(trifluoroacetate) (PIFA) have received a great deal of attention due to low toxicity, ready availability, easy handling, and reactivities similar to that of heavy metal reagents or anodic oxidation. In contrast to the widely explored phenolic oxidation using PIDA or PIFA, reactions of phenol ethers with hypervalent iodine reagents have been limited and have yielded mostly iodonium salts. We found unexpectedly that the reaction of p-substituted phenol ethers with PIFA in the presence of some nucleophiles in polar and poorly nucleophilic solvents such as 2,2,2-trifluoroethanol and 1,1,1,3,3,3-hexafluoro-2-propanol caused a novel and straightforward nucleophilic substitution reaction on the aromatic ring via a cation radical intermediate [ArH+.]. Successful application of PIFA-induced umpolung of electron-rich aromatic ring reactivity allowed intramolecular cyclization reactions of phenol ethers leading to novel and efficient preparations of synthetically useful products such as biaryl compounds, quinone-imines, and sulfur-containing heterocycles. Using these methods, the first total synthesis of potent cytotoxic marine alkaloid, makaluvamine F was also achieved.

Novel catalytic asymmetric sulfoxidation in water using the hypervalent iodine reagent iodoxybenzene.

A new catalytic asymmetric oxidation of sulfides to sulfoxides in water using the hypervalent iodine(V) reagent iodoxybenzene (PhIO2) has been developed. This methodology is distinctly different from the previously reported use of cyclodextrins or biological catalysts and provides a new route to asymmetric sulfoxidation in water.

Molecular Design, Characterization, and Application of Multiinformation Dyes (MIDs) for Optical Chemical Sensings. 3. Application of MIDs for λ(max)-Tunable Ion-Selective Optodes.

By utilizing "multiinformation dyes (MIDs)", which have plural spectral change characteristics such as an absorption maximum wavelength (λ(max)) shift based on a polarity change and an absorbance change due to protonation, novel λ(max)-tunable ion-selective optodes were proposed and prepared by employing MIDs with membrane solvents having different polarities. For controlling the detecting λ(max) of the optode, the novel polar membrane solvent [2-[[6-(2-nitrophenoxy)hexyl]oxy]methyl]isobutane-1,3-diol was designed and synthesized, which was used together with a typical membrane solvent nitrophenyl octyl ether. By mixing these two membrane solvents, the λ(max) position of the optode detection wavelength can be shifted and controlled and was successfully applied to a λ(max)-tunable Li(+)-selective optode based on a highly Li(+)-selective ionophore TTD14C4. The λ(max) tuning technique is useful for preparing an optode system using a low-cost light source such as a light-emitting diode or a popular laser.

Vector manometric study of the sphincter of Oddi in the dog: functional and morphological correlation.

The relationship between sphincter of Oddi pressure and the morphological structure of the sphincter was studied in eight dogs prepared with a duodenal cannula. Sphincter of Oddi manometry was performed in awake animals in three directions, ventral, left dorsal, and right dorsal, using a catheter with three radial side holes for recording at one level. The pressure in the ventral direction (26.6+/-1.06 mmHg) (mean+/-SEM) was significantly lower than that in the left and right dorsal directions (30.6+/-1.42 and 31.2+/-1.23 mmHg, respectively). This functional manometric difference in the three directions correlated closely with the morphological structure of the sphincter of Oddi; the sum of the thickness of the sphincter of Oddi muscle and duodenal proper muscle was greater on the dorsal than on the ventral side. To our knowledge, this is the first report of axial asymmetry in sphincter of Oddi pressure.

Molecular Design, Characterization, and Application of Multiinformation Dyes for Multidimensional Optical Chemical Sensings. 2. Preparation of the Optical Sensing Membranes for the Simultaneous Measurements of pH and Water Content in Organic Media.

Optical chemical sensing of pH and water content in organic solvents is proposed, using multiinformation dyes (MIDs) based on the support matrixes for the dyes. In this investigation, four kinds of merocyanine-type dyes having a polymerizable olefin unit as the MIDs were synthesized. These dyes were copolymerized with hydrophilic monomer molecules to obtain dye-immobilized optical chemical sensor (optode) membranes. In this case, selection of the monomer molecule gave optode membranes having different color change properties, because different monomer molecules provided different chemical environments around the immobilized dye. These optode membranes were used for the measurement of pH and water content in organic solvents. These membranes offered two-dimensional sensing information in one spectrum when they were employed for water content sensing in organic solvents, in which the maximum wavelength represents the water content and the absorbance at this wavelength represents the pH of the water present. These polymer membranes have a long lifetime, which can be adequate for practical use.

Uterine blood flow. Assessment in an intrauterine insemination program for unexplained infertility.

OBJECTIVE: To evaluate the diagnostic usefulness of color Doppler velocimetry for infertility treatment. STUDY DESIGN: Sixty-one women undergoing controlled ovarian hyperstimulation and intrauterine insemination with their husbands' semen due to unexplained infertility were enrolled in the study. The Doppler waveforms of the uterine artery, subendome-trial radial artery and intraovarian artery were analyzed around ovulation, and the calculated pulsatility indices (PIs) were correlated with subsequent pregnancy results. RESULTS: Those women who conceived exhibited a significantly lower uterine artery PI and higher frequency of positive diastolic blood flow in the subendometrial arteries shortly after ovulation. The PI of the intraovarian arteries prior to ovulation was also significantly lower in conception cycles than in nonconception cycles. Uterine artery PIs between different cycles correlated well in the same individual. Lower uterine artery impedance was noted in women receiving supplementation with human menopausal gonadotropins as compared to clomiphene citrate alone. CONCLUSION: Doppler velocimetry is a useful tool for evaluating uterine receptiveness in infertility treatment. Intrinsically poor uterine perfusion should be investigated in cases of unexplained infertility.

[A case of advanced breast cancer with multiple lung metastases responding well to postoperative combined administration of doxifluridine (5'-DFUR) and tamoxifen].

A 72-year-old female with right breast cancer having multiple lung metastases was treated by combined administration of 5'-DFUR at 800 mg/day, and tamoxifen, at 20 mg/day, after standard radical mastectomy. Plain chest X-ray and computed tomography examinations have shown complete disappearance of the multiple lung tumor since the therapy. No serious side effects have been observed during the treatment course, and there has been no definite evidence of tumor recurrence.

Squamous cell carcinoma of the splenic flexure of the colon: report of a case.

A 51-year-old Japanese man underwent resection of a tumor in the splenic flexure of the colon, which proved to be squamous cell carcinoma. At the time of presentation, the liver was found to have multiple metastases. On the 39th postoperative day, the patient died of liver failure. An autopsy demonstrated metastatic nodules on the pleura and parenchyma of both lungs, as well as in the liver, but failed to show any other primary squamous cell carcinoma. We emphasize that a meticulous search to disprove adenosquamous carcinoma is mandatory before a diagnosis of squamous cell carcinoma of the colon can be confirmed.

[Chemotherapy for advanced and recurrent cancer patients--the effect of combination chemotherapy using cisplatin, peplomycin, mitomycin C, adriamycin, and 5-fluorouracil].

According to the data obtained from the fundamental investigations using flow cytometry we designed the schedule of combination chemotherapy for solid cancer patients and we tried this therapy on 25 patients with non-curative, unresectable and recurrent cancers: 9 gastric, 5 colo-rectal, 3 esophageal, 3 pancreatic, 2 gall bladder, 2 lung and 1 breast cancer. The treatment was performed every 3 or 4 weeks as follows: CDDP 70 mg/m2 (d.i.), PEP 4 mg/m2 (i.v.) and MMC 4 mg/m2 (i.v.) on day 1, ADM 15 mg/m2 (i.v.) on day 4, and 5-Fu 250 mg/body (d.i.) every day. Among 22 patients evaluated completely, 1 complete response, 9 partial responses, 11 no changes, 1 progressive disease were obtained. The overall response rate was 45%. From the comparison of survival curves, survival rate was significantly better in patients responded to this therapy than in patients who did not respond to it (p less than 0.05). As for side effects, myelosuppression occurred in 19 patients (86%), increase of BUN and/or creatinine were observed in 3 patients (14%), increase of GOT and/or GPT were seen in 10 patients (45%), gastrointestinal symptoms and alopecia were observed in almost all patients, but all of these toxicity were transient and did not impede the continuous treatment.

[Experience with transvenous retrieval of a fractured IVH catheter from the superior caval vein--a study of the mechanism of catheter breakage by a model tension test].

An IVH catheter which was left in the superior caval vein was removed using a myocardial bioptome. It was accidentally broken when the patient unintentionally pulled it out. The cut surface was examined and it was confirmed that the IVH catheter could be broken irrespective of any defect of the catheter itself. To clarify the mechanism of catheter breakage, a model tension test was performed. The tensile strength and elongation were examined in 3 ways; first without binding, second with binding, third with binding and also pulling backward. The rate of tension was also varied from 100mm/min to 1,000 mm/min. It was found that the catheter was easier to break when pulled out faster, with binding, and pulled backward. When pulled forward, it was elongated and the site of breakage was not at the site of binding. However, when pulled backward, it was less elongated and the site of breakage was at the site of binding. An electron microscopic examination of the removed catheter revealed that the cut surface resembled that being pulled backward at a rate of 1,000 mm/min. The above suggests that, in this case, the IVH catheter was trapped between the clavicle and the 1st rib and pulled at an angle.

Clinical diagnosis of minute gastric cancer less than 5 mm in diameter.

When 58 minute gastric cancers less than 5 mm in diameter from 55 patients were classified into 22 of the single group (minute gastric cancer alone) and 36 of the multiple group (associated with other large gastric cancers), the preoperative correct diagnostic rate by x-ray was 22.7% and 11.1% in the single group and in the multiple group, respectively, with a total rate of 15.5%. The diagnostic rate by endoscopy, aided by endoscopic biopsy, was 95.5%, 13.9%, and 44.8%, respectively. Therefore, it appears that endoscopy and endoscopic biopsy are most efficient diagnostic tools for the detection of such minute gastric cancers. Since the detection of the depressed type (IIc) of minute gastric cancers is considered most significant because of their frequent submucosal invasion, their characteristic endoscopic findings are emphasized: (1) irregular and polygonal shape, (2) distinct depression, (3) clear demarcation, (4) nodular margins, and (5) moth-eaten appearance and abrupt thinning of the mucosal folds.

Intestinal metaplasia of the regenerative epithelia in 549 gastric ulcers.

Histopathologic changes in the regenerative epithelia of 549 foci of gastric ulcer were studied. About 70 per cent of the regenerative epithelia revealed intestinal metaplasia of the so-called complete or incomplete type. Parietal cells and chief cells were occasionally observed in the regenerative epithelia of ulcers located in fundic gland areas or at fundopyloric gland borders. It is possible that the regenerative epithelium frequently reverts to intestinal epithelium during the regenerative process, later redifferentiating into normal gastric mucosa or remaining as intestinal metaplasia and that, thus, only a few foci of intestinal metaplasia are precancerous lesions.

[Epidemiologic study of breast fluid in Japanese women].

Breast fluid was collected from 805 Japanese women using a negative-pressure breast-pump procedure. All subjects were non-lactating; there were 275 breast cancer patients and 530 healthy women. Women who secreted 20 microliters or more were classified as "secretors" (290/805, 36%); those who secreted less than 20 microliters to as "non-secretors". Breast cancer patients showed a significantly higher incidence of secretion, particularly in the diseased breast, than healthy women. Among secretors, the risk for breast cancer was high in those with earlier menarche, unmarried women, those with a smaller number of pregnancies and children and those with older age at their first delivery.