ß-Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation.

The Wnt/ß-catenin signaling is essential for various organogenesis and is often implicated during tumorigenesis. Dysregulated ß-catenin signaling is associated with the formation of endometrial adenocarcinomas (EACs), which is considered as the common form of endometrial cancer in women. In the current study, we investigate the downstream target of Wnt/ß-catenin signaling in the uterine epithelia and the mechanism leading to the formation of endometrial hyperplasia. We report that conditional ablation and activation of ß-catenin in the uterine epithelia lead to aberrant epithelial structures and endometrial hyperplasia formation, respectively. We demonstrate that ß-catenin regulates Foxa2 with its candidate upstream region for the uterine epithelia. Furthermore, knockdown of Foxa2 leads to defects in cell cycle regulation, suggesting a possible function of Foxa2 in the control of cell proliferation. We also observe that ß-catenin and Foxa2 expression levels are augmented in the human specimens of complex atypical endometrial hyperplasia, which is considered to have a greater risk of progression to EACs. Thus, our study indicates that ß-catenin regulates Foxa2 expression, and this interaction is possibly essential to control cell cycle progression during endometrial hyperplasia formation. Altogether, the augmented expression levels of ß-catenin and Foxa2 are essential features during the formation of endometrial hyperplasia.

Comparative study of low-dose pioglitazone or metformin treatment in Japanese diabetic patients with metabolic syndrome.

The aim of this study was to determine whether a relatively low dose of pioglitazone or metformin was effective in diabetic patients with metabolic syndrome. Fifty diabetic patients with metabolic syndrome were randomly assigned to a low-dose pioglitazone (15 mg/day) treatment group or a low-dose metformin (500 mg/day) treatment group. Drugs were administered for 12 weeks. Systolic and diastolic blood pressure, heart rate, body mass index, triglyceride (TG), HDL and LDL-cholesterol, fasting plasma glucose (FPG), fasting plasma insulin (IRI), postprandial glucose, and HOMA-IR in the 75gOGTT, HbA1c, high-sensitivity CRP (hs-CRP) determined by cervical artery echography, and pulse wave velocity (PWV) were measured before/after 12-week drug administration. Significant decreases in HbA1c and HOMA-IR were noted in the pioglitazone group, along with significant decreases in TG, AST, ALT, blood pressure, hs-CRP and PWV. Significant decreases in HbA1c, HOMA-IR, BMI and waist circumference were noted in the metformin group. The pioglitazone group significantly improved the values for ALT, systolic blood pressure, hs-CRP and PWV compared to the metformin group. However, the metformin group demonstrated significant improvement in BMI compared with the pioglitazone group. Using a low dose regimen, pioglitazone significantly improved blood pressure and hepatic function and may be more effective than metformin to reduce risk factors in Japanese diabetic patients with metabolic syndrome at preventing atherosclerosis.

Short communication: evidence for the presence of a putative odorant-binding protein in bovine colostrum.

Using a combination of PAGE and mass spectrometry for protein identification, we obtained evidence that a putative odorant-binding protein, designated hypothetical protein LOC517854, occurs in bovine colostrum. This protein, termed as a putative bovine colostral odorant-binding protein (bcOBP), consists of 172 AA residues, including a putative 16-AA signal peptide. The theoretical isoelectric point value and molecular mass of the full-length sequence of bcOBP were calculated to be 4.57 and 19604.18, respectively. The highest sequence similarity (83%) was observed with a potential pheromone transporter, Allergen Bos d 2. An odorant-binding protein derived from bovine nasal mucosa showed relatively low sequence similarity (52%) against bcOBP. Its biological function is unclear, but pheromone transport could be considered. This is the first report of a putative odorant-binding protein in bovine colostrum.

Binding affinity of GM3 lactone for influenza virus.

We investigated the interaction of GM3 lactone with influenza virus. The specific bindings of influenza virus and its hemagglutinin to GM3 lactone-containing mixed monolayers were studied by using a quartz-crystal microbalance. It has been known that gangliosides as receptors for influenza virus are also substrates for virus neuraminidase. GM3 lactone, however, was found to bind to influenza virus hemagglutinin, but not to be substrate for virus neuraminidase.

Naturally occurring ganglioside lactones in Minke whale brain.

Ganglioside lactones in Minke whale brain were analysed. In order to exclude the possibility of the artificial lactonization of gangliosides during the analytical procedures, lactone species were separated from their parent gangliosides at an early stage by DEAE-Sephadex A-25 column chromatography using a stepwise elution. Applying the improved method, GM41 lactones were found in grey and white matters of cerebrum and cerebellum, while GD3 monolactone was found only in cerebellar gray matter. The concentration of each ganglioside lactone was one thousandth of the parent ganglioside.

Quantitative measurements of the interaction between monosialoganglioside monolayers and wheat germ agglutinin (WGA) by a quartz-crystal microbalance.

Monosialogangliosides (GM1, GM2, GM3 and GM4) were reconstituted in lipid monolayers at the air-water interface. The binding amounts and the initial binding rates of wheat germ agglutinin (WGA) to the monosialoganglioside monolayers were quantitatively studied by use of a quartz-crystal microbalance (QCM). A QCM was horizontally attached to the monolayer from the air phase, and the binding behavior (mass increase) was followed by the frequency decrease of the QCM. WGA binding affinities for the ganglioside monolayers were influenced by hydrophilic head groups of lipid matrices, densities of gangliosides, and sequences of oligosaccharide in gangliosides. Binding of WGA to the gangliosides reconstituted in a phosphatidylcholine (sphingomyelin and distearoylphosphatidylcholine) matrix was strongly suppressed, but not in a neutral glycolipids (GlcCer, GalCer, and LacCer), dipalmitoylphosphatidylethanolamine, and dipalmitoylphosphatidylethanolamine matrix. WGA showed high affinity for monolayers containing 20 mol% gangliosides, but only low affinity for 100% ganglioside monolayers. WGA preferably binds to gangliosides in the following sequence: GM3 > GM4 >> GM2 = GM1. No affinities of WGA for GM2 and GM1 were observed. The combined techniques of monolayer and QCM have the advantages of investigating recognition properties of gangliosides.

Observation of ganglioside lactone formation with CD spectrometry.

Monolactone (NeuAc1-9NeuAc linkage) formation of a ganglioside, GD1b, was observed at 20 degrees C on solutions ranging in concentration from 0.008 to 1.7 mM and in pH from 2 to 8.1, by following the change of ellipicity at 235 nm, where lactonized gangliosides showed a strong Cotton effect. The lactonization was found to be a first-order reaction in both GD1b and H+ in the initial stage but was affected later by a backward reaction, hydrolysis of the lactone linkage. The rate constant was 0.08 h-1 at pH 3. At this pH the reaction went close to equilibrium in 24 h at approximately 70% lactonization. At pH higher than 5.9 no change was observed in the ellipticity within 30 h, suggesting the possibility that at most 0.6% of the ganglioside lactonized. Lactonization of another ganglioside, GD3, in glacial acetic acid was observed with a 0.2-mm cell, agreeing well with a reported result.

A comparative study on ceramide composition of cetacean brain gangliosides.

1. Ceramide composition and N-glycolylneuraminic acid content of gangliosides from gray and white matters and myelin of cerebrum and cerebellum were analyzed in eight species belonging to the suborder Odontoceti and two species to Mystacoceti. 2. The most characteristic feature was high contents of C20:0 (10-40%) and C24 species (5-40%). 3. Content of hydroxy fatty acid of C24 species was higher in cerebellum (5-20%) than cerebrum (0-3%). 4. Major component of long-chain base was dC18:1 (70-90%). 5. N-glycolylneuraminic acid was found in sperm whale, Dall's porpoise and killer whale (0.1-1.7%).

The characteristic negative Cotton effect of ganglioside lactones observed by circular dichroism spectrometry.

Circular dichroism spectrometry was applied to gangliosides and their lactones and revealed that the lactones have a characteristic strong negative Cotton effect around 235 nm. Four monolactones and two dilactones, which were formed from GM4, GD3, and GD1b, gave molar ellipticities at the wavelength in magnitude of 10(4), while their parent gangliosides, along with other gangliosides such as GM3, GM1, GD1a, GT1b, and GQ1b, showed no distinct feature. Two ganglioside esters, GM4-methyl ester and O-Ac-GT1b did not show the Cotton effect. The molar ellipticities had an additivity with respect to the number of lactone rings. The Cotton effect was attributed to the carbonyl group on the lactone ring.

Metastatic intracranial carcinoid with immunohistochemical observation. Case report.

A case of metastatic carcinoid tumor in the right occipital lobe originating from a primary tumor in the right colon is reported in a 68-year-old man. The tumor had a high bromodeoxyuridine labeling index. Although immunohistochemical studies of the tumor specimen showed positive reactivity for serotonin and somatostatin, blood levels of serotonin and urinary 5-hydroxyindoleacetic acid content were normal. This suggests that coexistence of somatostatin with serotonin in the tumor tissue might lead to inhibition of serotonin release by "autocrine regulation." The neurological complications of carcinoid tumors, including intracranial metastasis, are discussed briefly.

Characterization of ganglioside GM4 lactones isolated from the whale brain.

Two novel ganglioside lactones were isolated from the brain of Bryde's whale (Balaenoptera edeni) and characterized. These gangliosides migrated above GM4 and were designated M4-1 and M4-2 in the order of location from the bottom of the TLC plate. These gangliosides were converted to GM4 by mild alkali treatment. Although M4-1 and M4-2 contained 1 mol each of N-acetylneuraminic acid and galactose, they behaved as neutral lipids on ion-exchange chromatography. Inner ester linkages were found in these gangliosides by secondary ion mass spectrometry and infrared spectroscopy. Two-dimensional J-correlated proton NMR spectra revealed that an inner ester linkage was formed in M4-1 between the sialic acid carboxyl group and the C-4 hydroxyl group of the galactosyl residue and another inner ester linkage was formed in M4-2 between the sialic acid carboxyl group and the C-2 hydroxyl group of galactose.

[Multiple intracerebral hemorrhages immediately after surgical excision of middle fossa arachnoid cysts and evacuation of chronic subdural hygroma. Case report].

A 49-year-old male was hospitalized with a 1-month history of persistent headache and vomiting. Computed tomography (CT) revealed left middle fossa arachnoid cysts and a chronic subdural hygroma. The cysts were excised after evacuation of the subdural hygroma. Postoperatively, the patient did not regain consciousness and CT showed multiple intracerebral hemorrhages in both the supra- and infratentorial spaces. Three months postoperatively, he was discharged with mental deficits and right hemiparesis. A review of the literature indicates that the possible pathogenic mechanism in this case was a sudden increase in cerebral blood flow due to faulty autoregulation. This devastating complication may have been avoided by simple drainage of the subdural hygroma, perhaps with the addition of cyst-peritoneal shunting.

[Recurrent meningioma with malignant changes and extracranial multiple metastases].

A case of recurrent meningioma with malignant change and extracranial multiple metastases is reported. A 51-year-old female was operated on and left parasagittal meningioma was extirpated by Simpson grade II. Histological diagnosis was fibroblastic and transitional meningioma with slight atypism. Six years later, however, the tumor (transitional meningioma with slight mitosis) recurred in the same portion and was removed again by Simpson grade II. Further more, four years after the second operation, bilateral parasagittal meningioma (atypical meningioma; transitional type) was extirpated by Simpson grade I including superior sagittal sinus and falx. Only eight months after the last operation, a few tumors with central necrosis were demonstrated in the bilateral parasagittal area on a computerized tomography scan and she received radiation therapy. But the tumor had metastasized to the extracranial multiple organs including lungs, liver, pancreas, adrenal gland, muscles, multiple bones and lymph nodes. Post mortem diagnosis was malignant meningioma. We reviewed and discussed the characteristics of metastasizing meningioma, the effectiveness of radiation therapy on the prevention of recurrence of meningioma and the curative effect of radiation therapy for recurrent or metastasized meningioma.

Anthropometric relevance on sublabial transseptal transsphenoidal hypophysectomy in the Asiatic type of skull.

In order to preoperatively estimate the width of the operating field during transphenoidal hypophysectomy, we measured the distance between the right and left medial pterygoid plates in 27 normal adults and 11 patients with pituitary adenoma from anteroposterior tomograms. In normal subjects, the mean distance was about 3.2 cm. The distance in patients with acromegaly was not wider than that in normal subjects, but 1 case with giantism showed a much wider distance of 4.1 cm. The measurement of the actual operating field was 2.0 cm in width, about 1.0 cm narrower than the preparative tomogram calculations.

[Traumatic spinal subarachnoid hematoma presenting with Brown-Séquard syndrome].

We report a rare case of traumatic spinal subarachnoid hematoma with Brown-Séquard syndrome following hyperextension injury. A 43-year-old man was admitted to our hospital four days after hyperextension cervical injury complaining of nuchal pain, left hemiparesis and dysesthesia of the left arm. On the third hospital day, neurological examination revealed left C2,3 level Brown-Séquard syndrome. High cervical plain CT scan showed a high density area in the left spinal canal from C1 vertebral body level to C2-3 intervertebral level. Emergency operation was performed and a left-sided subarachnoid hematoma was removed. The left C2 and C3 nerve roots were markedly stretched and the cord was shifted to the right. Neither vascular abnormality nor tumor was found and no traumatic change was seen on the cord. The Brown-Séquard syndrome disappeared soon after surgery, but the weakness of the left arm and anesthesia at the level of left C2 dermatome remained until six months after operation. Review of the literature revealed no such a case as the one in which the patient developed a spinal subarachnoid hematoma following hyperextension injury without any preexisting disease or injury of the spine. Brown-Séquard syndrome caused by spinal subarachnoid hematoma was not found on the literature either. So we believe that this is the first report of case of such lesion. The mechanism of subarachnoid clot formation on hyperextension injury may be due to transient dislocation of the spine with tearing of the anterior longitudinal ligament or to crushing of the cord between the ligamentum flavum, which bulged forward on hyperextension, and the posterior aspect of the vertebral body.(ABSTRACT TRUNCATED AT 250 WORDS)

[Determination of blood polyamines in patients with brain tumor -with special reference to relationship between varieties of tumors and concentrations of blood spermidine and spermine (author's transl)].

Examination of blood polyamines in 38 patients with brain tumor and 17 normal volunteers was carried out by columnar chromatography--cellulose acetate membrane electrophoresis. The upper limits of the normal values; M.+2S.D. of the blood polyamine concentrations in 17 normal volunteers, were less than 2.1 mg/ml for spermidine, less than 1.6 mg/ml for spermine, and less than 2.2 mg/ml for spermidine plus spermine. The values of blood polyamines in 21 cases with glioma were significantly higher than those in normal subjects (p less than 0.01). And in 14 out of them, the concentrations of the blood polyamines were higher than the maximum normal value. In one case with reticulum cell sarcoma, the concentrations of the blood polyamines were remarkably increased. In 2 out of 4 cases with metastatic brain tumor the concentration of the blood polyamines were higher than the upper limit of normal amount, and values of the blood polyamines in 4 cases with metastatic brain tumor were significantly higher than those in normal volunteers (p less than 0.05). In none of 2 cases with pituitary adenoma, 3 cases with meningioma, 4 cases with neurinoma, one case with hemangioblastoma, and one case with pinealoma, the values of the blood polyamines were significantly higher than those in normal volunteers. The CSF samples obtained from 9 patients with brain tumor, consisted of 6 gliomas (glioblastoma multiforme 2, anaplastic glioma 4), 1 teratoblastoma, 1 von Recklinghausen's disease (neurinoma and meningioma), and 1 craniopharyngioma, were analyzed for detection of polyamines, but no detectable amount was present in those cases.