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This study assessed the effect of Kaempferia parviflora, also known as black ginger (BG), and its ethanol extract (BGE) on peroxisome proliferator-activated receptor (PPAR) γ agonistic activity, glucose tolerance, fat accumulation, and lipids-induced hypertriglyceridemia in mice. PPARγ ligand-binding capacity in vitro and polymethoxy flavone contents were highly observed in organic solvent extracts. In an animal experiment A, male diabetic Nagoya-Shibata-Yasuda mice were divided into five dietary groups and fed each diet for 8 weeks: AIN-93G diet (low-fat [LF] diet), high-fat (HF) diet, HF diet supplemented with 1% BG, HF diet supplemented with 0.19% BGE, and HF diet supplemented with pioglitazone (PPARγ agonist, 3 mg/kg/day) as a PPARγ agonistic positive control. As determined from glucose and insulin tolerance tests, plasma glucose levels were improved in the BG and BGE groups. The BGE extract suppressed fat accumulation in adipose tissues, liver, and muscles without changing the plasma adiponectin level. In an animal experiment B, in order to investigate the effect of BG and BGE on lipid-induced hypertriglyceridemia, male ddY mice were divided into three test groups: control, BG-administered group (500 mg/kg), and BGE-administered group (100 mg/kg). The plasma triacylglycerol level was not different among the groups during the lipids administration test. These results conclude that the BGE extract containing several kinds of polymethoxy flavones showed PPARγ ligand-binding capacity in vitro and prevented obesity and insulin resistance independent of adiponectin secretion in mice. PRACTICAL APPLICATION: Kaempferia parviflora, also known as black ginger (BG), is often used as a folk medicine and a functional food material to prevent metabolic syndrome mainly in Asian regions. Here, we have clarified that ethanol extract from BG (BGE) contains several kinds of polymethoxy flavones to show PPARγ ligand-binding capacity and is an active extract for the improvement of obesity and insulin resistance. The BGE is expected to be applied for functional food materials in health food markets. Also, polymethoxy flavones to show PPARγ ligand-binding capacity can be generally applied as a physiological active compound of functional food supplements.

To investigate the role of interleukin-1 related substances in amniotic fluid in normal term labor without intrauterine infection.Amniotic fluid samples were collected from forty-one patients with various backgrounds. A novel pre-assay treatment using Frigen II was introduced to improve the recovery rates of cytokines, i.e., interleukin-1alpha, interleukin-1beta and interleukin-1 receptor antagonist, prior to ELISA assay. Urine samples from newborn infants were also tested.The concentrations of interleukin-1alpha, interleukin-1beta and interleukin-1ra were significantly higher in samples from normal vaginal delivery. The higher levels of interleukin-1alpha were also observed in samples from preterm labor without infection. Preterm infants produced more of interleukin-1 receptor antagonist in urine compared with term infants.This study provides evidence of the possible involvement of interleukin-1 related substances in labor without signs of infection. The data from newborn urine suggests that amniotic interleukin-1ra originates from the fetus. However, amniotic fluid interleukin-1alpha and interleukin-1beta may be derived from maternal tissue, such as decidua.

Oxidative stress in cancer patients has been demonstrated to be partly mediated by neutrophils. Although it is reported that natural antioxidants, such as green tea extract, reduce oxidative stress, there is limited evidence of their effects in cancer patients. This study aimed to determine the effect of green tea extract on reactive oxygen species produced by neutrophils from cancer patients.Peripheral blood samples were obtained from eighteen patients with advanced cancer. Green tea extract was added to the blood samples with luminol on Mebiol gel, and luminol-dependent chemiluminescence was measured to monitor the production of reactive oxygen species from migrated neutrophils into the gel, at 37°C.Luminol-dependent chemiluminescence was significantly down-regulated in the presence of green tea extract in a concentration-dependent manner.These results indicate the antioxidant effect of green tea extract on reactive oxygen species produced by neutrophils, which may be effective in reducing oxidative stress in cancer patients.

The cytokine interleukin-1 (IL-1 beta) increased prostaglandin production by decidual stromal cells in culture in a time and dose dependent manner. Optimum conditions for stimulation were found to be for 24 hours at a concentration of 100 pg IL-1 beta/ml. An apparent increase in cyclo-oxygenase enzyme synthesis accompanied the increase in prostaglandin production, and both changes were inhibited by the protein synthesis inhibitor cycloheximide. This implicates protein synthesis in the stimulatory effects of IL-1 beta, which may be mediated through the increase in cyclo-oxygenase enzyme. A pre-incubation period of 72 hours was found to be necessary to observe the stimulatory effect of IL-1 beta on prostaglandin production, but this did not seem to be due to any change in the sensitivity of the cells to IL-1 beta; the increase in the number of cyclo-oxygenase positive cells was the same if IL-1 beta was added on day 1, day 2 or day 3 of culture, even though prostaglandin production was not stimulated on day 1 or day 2. Cycloheximide increased prostaglandin production on the first two days of culture and had no effect on the third day of culture. This was interpreted as indicating that a factor inhibiting cyclo-oxygenase activity was synthesised during the initial period of culture, which prevented any increase in prostaglandin production following the increase in enzyme synthesis.

To elucidate the morphogenesis of cornoid lamellae (CL) in porokeratosis, skin lesions of three cases of disseminated superficial actinic porokeratosis and a case of linear porokeratosis were examined. By N-(7-dimethylamino-4-methyl-3-coumarinyl)maleimide staining, SH groups were present in the living layer of the epidermis beneath CL and irregularly disappeared at the bottom of CL, whereas SS linkages appeared in dyskeratotic cells in the living layer and in the irregularly shaped cell membranes of the horny cells. Epidermis beneath CL showed an increased and irregular involucrin expression. Ultrastructurally, the living keratinocytes contained many cytoplasmic vacuoles and had a smaller number of lamellar bodies than normal. Intercellular lamellar sheets were incompletely formed. The dyskeratotic cells and the lower horny cells contained many small vacuoles but formed a marginal band. The horny cells of CL also formed a marginal band and, further, a keratin pattern. CL may be formed by hyperproliferative atypical kertatinocytes which keratinize rapidly and irregularly and show defective desquamation due to the paucity of intercellular lamellar sheets.

The decidua has been implicated in the control of human labour, particularly through changes in prostaglandin production, but this tissue contains a number of different cell types. A density gradient system was used to obtain two populations of cells from term human decidua, and these populations were characterised. The more dense cells (population B) was a mixed population, predominantly macrophages (80%), but small numbers of T- and B-lymphocytes were also present, as identified by immunocytochemistry. Most of these cell types also contained detectable levels of cyclooxygenase enzyme. The less-dense cell population (population A) did not contain significant numbers of the above cell types and released prolactin, suggesting that they were decidual stromal cells. This preparation of decidual stromal cells may be of use in defining the functions of these cells in labour.

An inhibitor of prostaglandin synthetase which catalyzes the conversion of arachidonic acid into prostaglandin E2 was partially purified from the 105 00 × g supernatant fraction of the human decidual cell homogenate. By means of ammonium sulfate fractionation, Mono Q ion-exchange chromatography, and gel filtration chromatography, the inhibitor was purified about 15-fold, giving a preparation with a molecular weight of 55–60 KDa. The 50% inhibitory concentration of the purified substance was approximately 0.2 mg/ml. The inhibitor may play a role in suppression of prostaglandin production by decidua in early pregnancy.

We evaluated functional and morphological outcomes of transvaginal anterior levatorplasty with posterior colporrhaphy for symptomatic rectocele. Ten women (median 68 years) underwent transvaginal anterior levatorplasty with posterior colporrhaphy for symptomatic rectocele. Symptoms and continence were monitored before and after surgery. Manovolumetric study and defecography were performed in 9 of 10 patients before and 3–6 months after surgery. Twenty-one females without anorectal diseases were used as controls in manovolumetric study. The patients were followed up after a median of 89 months (range, 3–103). Main symptoms (defecatory disorders in 9 patients, vaginal mass in 6, perineal discomfort in 2) disappeared after surgery. Six patients performed digitation preoperatively and gave up digitation on defecation after surgery. Stool incontinence disappeared in 4 of 5 preoperatively incontinent patients (Cleveland clinic score, 5–12) and continence score improved from 5 to 2 in the remaining patient. Three patients with urinary cough incontinence preoperatively did not experience incontinence after surgery but cough incontinence occurred occasionally in an 81-year-old patient postoperatively. Rectocele demonstrated on defecography disappeared postoperatively in all 9 patients who underwent defecography. High threshold volume and maximum tolerable volume, which were observed preoperatively, decreased to control levels after surgery. Transvaginal anterior levatorplasty with posterior colporrhaphy might be an option for symptomatic rectocele to improve anorectal and urinary dysfunctions with morphological disorders.

To examine the feasibility of using three-dimensional (3D) ultrasound (US) guidance in routine embryo transfer (ET) procedures.Seventy-five ETs were performed using a 3D US scanner to locate the catheter tip in the uterine cavity.Three-dimensional ultrasound could show the exact position of the tip of the catheter in the uterine cavity quickly enough in most cases. It should be used in ET for seeking an optimal transfer area in the uterine cavity to assist in achieving high success rates and less complications.

We reported a 50-year-old woman with a history of mixed connective tissue disease. She had two episodes of meningitis-like symptoms after taking famotidine and tiquizium bromide for treatment of gastric ulcer. From CSF findings (elevated pressure, increase of protein, polymorphonuclear pleocytosis, negative culture) and result of famotidine challenge test, we diagnosed her as a drug induced aseptic meningitis. Because she had taken tiquizium bromide several times previously without any side effects, we concluded that famotidine was a causative drug. She was recovered without sequelae within a few days following cessation of these drugs. This is the first report of H2-blocker induced aseptic meningitis. When we encounter a patient with aseptic meningitis who presents polymorphonuclear pleocytosis in CSF, we should suspect drug induced aseptic meningitis and take a history of drug medication including H2-blocker.

A weekly infusion of high dose 5-fluorouracil by way of the hepatic artery has been performed in 23 cases with synchronous metastasis from colorectal cancer since 1993. The prognosis in these cases was compared with 94 cases treated without infusion chemotherapy in 94 cases before 1992. The overall one-year and three-year survival rate was 64.8% and 30.2%, respectively, in cases with infusion chemotherapy. The one-year and three-year survival rate was 42.8% and 18.6%, respectively, in cases without infusion chemotherapy. Overall survival rate was significantly different between cases with and without infusion chemotherapy (p0.05). In conclusion, weekly infusion chemotherapy resulted in a better survival rate than without infusion chemotherapy.

In line with various protocols for chemotherapy of ovarian carcinoma, we used EP (etoposide-cisplatin or carboplatin) therapy in 10 patients with clear cell adenocarcinoma as the first line chemotherapy. Four of these cases were in advanced stage at IIIc, and had residual tumor after the operation. One of these patients with measurable tumor responded to semi-high dose treatment, and 5-days of continuous infusion of etoposide resulted in CR. Three cases of a patient at the stages of Ic and IIc are in disease free status after two years of standard-dose EP therapy. Therefore, high-dose EP therapy might be an effective chemotherapy for some patients with ovarian clear cell adenocarcinoma.

A 65-year-old woman was admitted to our hospital for evaluation of multiple liver tumors following endoscopic polypectomy for rectal polyp a year earlier. The polypectomy specimen was reexamined and showed inclusion of a carcinoid tumor 3 mm in diameter. The perirectal lymph node was palpated by digital examination on readmission. The patient died one mouth after readmission due to liver failure. Autopsy revealed metastatic carcinoid tumor in the liver and perirectal nodes.

We report two brothers with familial Creutzfeldt Jakob disease (CJD) having a heterozygous point mutation at codon 200 of the prion protein gene (Glu--Lys): CJD200. The brothers were born in Kitakoma-gun, Yamanashi Prefecture. Patient 1, a 62-year-old man, developed CJD in 1995 and died nine months later. Patient 2, his brother, developed CJD200 at the age of 58 in 1982 and died 13 months later. They both exhibited rapidly progressive dementia with myoclonus and periodic synchronous discharges on electroencephalograms and became bedridden with three or four months. DNA analysis of peripheral blood cells of patient I showed a point mutation in the prion protein gene at codon 200: GAG--AAG (Glu--Lys). Five families with CJD200, 11 patients, have been reported in Japan to date, and nine of the patients from four families were born in Yamanashi Prefecture and vicinity. Our patients were born in the same area. We suspect that there is a cluster of CJD200 in Yamanashi Prefecture and vicinity. In Europe and America the phenotype of CJD200 has been reported to be heterogeneous, whereas the clinical features in Japanese cases are fairly homogeneous. We suspect that these patients have a common ancestor with a codon 200 mutation, and that that explains why the phenotypes are homogeneous.

A 49-year-old female presented with a low abdominal tumor. Before operation, she had neither evidence of androgen excess nor abnormal tumor marker values, but US, CT and MRI findings strongly suggested the possibility of a malignant ovarian tumor. Her operative findings were as follows: a goose egg-sized main tumor in the low abdomen, with a walnut-sized tumor in the right side, which grew around the right ureter, causing right non-functional kidney. Pathological examination revealed her tumor was a very rare type of malignant Sertoli-Leidig cell tumor with pelvic lymph nodes metastases. Most patients with this disease usually have good prognoses, but with metastasis or recurrence, no therapy is as effective as in epithelial ovarian cancer. In this case, we selected a new combination chemotherapy of CBDCA, Etoposide and Epirubicin, considering current changes in the chemotherapy for ovarian germ cell tumors and Sertoli-Leidig cell tumors of testis. Now, 1 year and 4 months after operation, she has no evidence of recurrence or metastasis. This study proposes a new, presumably more effective chemotherapy for an ovarian malignant Sertoli-Leidig cell tumor.

In an attempt to evaluate the risks and benefits of human menopausal gonadotrophin (hMG) therapy for patients with unexplained infertility, the response and outcome of hMG therapy for anovulatory patients and ovulatory patients with unexplained infertility were analyzed in a group of successful cases of pregnancy. The number of follicles grown and the total doses of hMG were not significantly different in the two groups. The rate of spontaneous abortion in unexplained cases was twice as high (13.2%) as in anovulatory cases. However, the rate of multiple pregnancy was 8.8% for unexplained cases which was significantly lower than that for anovulatory cases (39.0%). In addition, ovarian hyperstimulation syndrome (OHSS) occurred in 11.8% of unexplained cases and that was much lower than that for anovulatory cases (25.8%). This study justifies the application of gonadotrophin therapy to ovulatory patients with unexplained infertility in terms of the risks and benefits of the therapy in achieving pregnancy.

In order to clarify the possible involvement of lipoxygenase metabolites of arachidonic acid (AA) in implantation, monohydroxylic acid production was examined using human endometrium and decidua in early pregnancy. As 14C-AA was mainly converted to 12-hydroxyeicosatetraenoic acid (12-HETE) as well as prostaglandins (PGs) by the microsomal fraction of the endometrium, a subsequent study was carried out on the endometrium (at various stages) and decidua in early pregnancy using tissue incubation and high performance liquid chromatography (HPLC) analysis for 12-HETE. The amounts of 12-HETE released into the culture medium by proliferative and secretory endometrium were 165.1 ± 123.4 (ng/mg. protein/24 h, mean ± SD) and 502.3 ± 127.2, respectively, whereas, decidua produced a smaller amount of 12-HETE that declined as gestation progressed. This lipoxygenase product as well as PGs might have a role in implantation.

Intact decidual stromal cells and macrophages metabolized 3H-prostaglandins E2 and F2 alpha although the rate of metabolism of both prostaglandins was higher in the decidual macrophages than in decidual stromal cells. PGE2 was metabolised mainly to 13,14-dihydro-15-keto-PGE2 together with smaller quantities for PGB2 and 13,14-dihydro-15-keto-PGA2, whereas PGF2 alpha was metabolised to 13,14-dihydro-15-keto-PGF2 alpha, PGE2 and PGB2, and it seems that similar metabolic pathways were present in both cell types. The half-lives of both prostaglandins (8.8 +/- 3.4 h for PGE2 and 15.0 +/- 8.2 h for PGF2 alpha sigma in the presence of decidual stromal cells show that during incubations lasting more than a few hours significant metabolism of prostaglandins, especially PGE2, will occur, and that this must be allowed for in any assessment of total prostaglandin production by cultured decidual cells. One of the 6 tissue samples examined metabolised both prostaglandins very rapidly, such that the half-lives were less than 2 h. This may be the result of the presence of very high levels of metabolic enzymes, since the overall pattern of metabolites was similar to that from the other 5 samples.

Term decidual stromal cells metabolized extracellular arachidonic acid to cyclo-oxygenase, lipoxygenase and epoxygenase products. Prostaglandins were the major metabolites from extracellular arachidonic acid. In contrast, intracellular arachidonic acid was metabolized mainly to an epoxygenase product, together with some lipoxygenase products. Decidual macrophages showed similar results, though these cells had higher production rates per cell of most metabolites. The calcium ionophore A23187 increased the levels of arachidonic acid released from the intracellular stores of decidual stromal cells and had variable effects on the production of cyclo-oxygenase, lipoxygenase and epoxygenase metabolites. Less than 15% of the total metabolites released from A23187-stimulated cells were cyclo-oxygenase products, which suggested that the cyclo-oxygenase products released by decidual stromal cells or macrophages may be mainly derived from extracellular arachidonic acid. This implies that the regulation of decidual cyclo-oxygenase may have a major role in determining prostaglandin output from this tissue.

An epidemiological study was performed with respect to Creutzfeldt-Jakob disease in a designated area in Japan. The subjects were observed in a small rural prefecture where the population generally remains within a limited radius throughout their lives. The patients'' life-styles in each area were investigated in detail. Nine cases appeared in 11 years; 6 were definitive and 3 probable. They were all of the subacute type; there were no noteworthy sexual differences, age of onset, course and/or past histories. Three of the nine cases came from two families; the relationship between familial and isolated cases was examined. Revealed facts and time-space clustering were investigated statistically, but no indication of natural transmission was observable.

This report describes a female patient with childhood form of acid maltase deficiency who survived till fifteen years old. Although acid alpha-1,4-glucosidase was deficient in the liver, kidney, skeletal and cardiac muscles, neutral alpha-1,4-glucosidase was present in normal concentrations in those organs. On light microscopic examination, numerous intracytoplasmic vacuoles containing acid phosphatase positive granules and PAS positive materials were present in both type 1 and 2 A fibers, predominantly in the latter. The striking finding in the present case was a selective type 2 fiber atrophy with type 2 B fiber deficiency believed to result from type 2 motor neuron dysfunction in the spinal cord. Electron microscopic study revealed extensive glycogen particle accumulation, autophagic vacuoles and myelin figures in the muscle fibers.

A 52-year-old woman visited us complaining of a recurrent vaginal tumor, which was diagnosed histologically as malignant fibrous histiocytoma of the vagina. Computed tomography revealed multiple metastatic lesions in the liver, lymph nodes and vertebrae. The patient was treated with combination chemotherapy consisting of cyclophosphamide, adriamycin and cis-platinum, but the tumor did not yield readily to the treatment. We believe that this is the first reported case of this tumor in this location in Japan.