Clinical significance of pyrimidine nucleoside phosphorylase (PyNPase) in breast cancer

To clarify the clinical significance of pyrimidine nucleoside phosphorylase (PyNPase) activity in breast cancer, we examined the possible correlation of PyNPase activity to clinicopathological features and prognosis in twenty-one patients with primary breast cancer from April 2000 to December 2001. Flow signals of tumors were analyzed by Power Doppler sonography (PDUS), and maximal velocity (V(max)) was calculated. PyNPase activity of resected specimens was assayed by ELISA method. PyNPase activities in resected cancerous tissue were 156.9+/-63.5 unit/mg (mean+/-SD), which were significantly higher than that in normal tissue (19.0+/-18.1 unit/mg, p<0.0001). PyNPase activity was positively correlated with tumor size (r=0.496, p=0.026) and V(max) (r=0.498, p=0.021). The disease free survival rate was significantly lower in the high PyNPase activity group than in the low PyNPase activity group. In overall survival rate, there was no significant difference between the high and low PyNPase activity groups. In the multivariate analysis, PyNPase activity was an independent predictor of postoperative recurrence (p=0.032). We suggest that PyNPase activity is associated with progression and proliferation of breast cancer, and that it may be useful for prediction of the prognosis.     

A case of immotile cilia syndrome and a review of Japanese cases

A case of immotile cilia syndrome (ICS) is presented. A 34-year-old male, who had suffered from recurrent bronchitis, sinusitis and otitis media since early childhood, was admitted to Keio University Hospital complaining of productive cough and infertility. A saccharin test showed prolonged nasal clearance time, and semen analysis revealed immotile sperm. By electron microscopic observation of cilia of the nasal mucous epithelium and the sperm, inner and outer dynein arm defect, abnormal microtubular arrangement and compound cilia were detected and he was diagnosed as ICS. Thirty eight Japanese cases of ICS collected from the literature were analyzed concerning clinical manifestations, airway clearance, family history and ciliary ultrastructural abnormalities (Table 2, 3). Recurrent bronchitis, male infertility, chronic sinusitis, otitis and decrease in airway clearance were very common in these patients. Female infertility was more common than anticipated. The prevalence rate of situs inversus was more than 50%, probably due to more attention having been paid to Kartagener's syndrome in Japan. Recent studies show that the cilia of this syndrome is not always immotile but characterized by hypomotility or asynchrony, and have attempted to determine the relationship between each ciliary ultrastructural abnormality and motility pattern. It is necessary that more patients including incomplete and mild cases should be investigated.     

CDKL5 alterations lead to early epileptic encephalopathy in both genders

Purpose: Genetic mutations of the cyclin‐dependent kinase‐like 5 gene (CDKL5) have been reported in patients with epileptic encephalopathy, which is characterized by intractable seizures and severe‐to‐profound developmental delay. We investigated the clinical relevance of CDKL5 alterations in both genders. Methods: A total of 125 patients with epileptic encephalopathy were examined for genomic copy number aberrations, and 119 patients with no such aberrations were further examined for CDKL5 mutations. Five patients with Rett syndrome, who did not show methyl CpG‐binding protein 2 gene (MECP2) mutations, were also examined for CDKL5 mutations. Key Findings: One male and three female patients showed submicroscopic deletions including CDKL5, and two male and six female patients showed CDKL5 nucleotide alterations. Development of early onset seizure was a characteristic clinical feature for the patients with CDKL5 alterations in both genders despite polymorphous seizure types, including myoclonic seizures, tonic seizures, and spasms. Severe developmental delays and mild frontal lobe atrophies revealed by brain magnetic resonance imaging (MRI) were observed in almost all patients, and there was no gender difference in phenotypic features. Significance: We observed that 5% of the male patients and 14% of the female patients with epileptic encephalopathy had CDKL5 alterations. These findings indicate that alterations in CDKL5 are associated with early epileptic encephalopathy in both female and male patients.     

The impact of rituximab prophylaxis on hepatocellular carcinoma recurrence after living donor liver transplantation

Aim: Rituximab is administered for ABO blood type incompatibility or donor-specific anti-HLA (human leukocyte antigen) antibody-positive liver transplantation (...     

Role of bradykinin in the vascular permeability response induced by carrageenin in rats.

1 Bradykinin in carrageenin-induced inflammatory pouch fluid was measured by an enzyme immunoassay method. 2 The bradykinin showed a single peak in the 30-60 min period after the challenge and then decreased quickly, and there was a correlation between the bradykinin level and exudation of fluorescein-labelled bovine serum albumin in the first 60 min period. 3 Captopril (an inhibitor of kininase II) elevated both the bradykinin level in the inflammatory pouch fluid and vascular permeability, while DL-2-mercaptomethyl-3- guanidinoethylthiopropanoic acid (an inhibitor of kininase I) had no effect. 4 Soybean trypsin inhibitor (SBTI) inhibited the vascular permeability response in parallel with the decrease in the bradykinin level. 5 A bradykinin-degrading activity appeared in the pouch fluid within 1 h after the challenge and increased with time. 6 In the period of 3.5-4 h, bradykinin levels were suppressed below the sensitivity limit of the assay, i.e. 0.07 nm ml-1, in spite of active generation. This was because degradation of bradykinin was very rapid in this late stage. Nevertheless, bradykinin still played a definite role in sustaining a high level of vascular permeability response in the late stage in conjunction with prostaglandins.     

An application of the biotic ligand model to predict the toxic effects of metal mixtures

The rapidly developing biotic ligand model (BLM) allows us to predict the toxicity of heavy metals in water of various chemistries; however, the current BLM predicts the toxicity of a single metal and not the toxic effects of metal mixtures. The toxic mechanisms of heavy metals are not yet completely understood, but hypocalcemia is suggested to be the most likely toxic mechanism for some metals. The BLM, which predicts the toxicity of metals by the amount of metals binding to ligand, is modified to predict the toxicity by the proportion of nonmetal binding ligand that is available for calcium uptake under the assumption that the organisms die because of hypocalcemia when so few ligands are available for calcium uptake. Because the proportion can be computed when multiple metals are present, the toxic effects of metal mixtures can be predicted. Zinc, copper, and cadmium toxicity to rainbow trout (Oncorhynchus mykiss) are considered. All data are collected from the literature, and a meta-analysis using the modified version of the BLM is conducted. The present study found that the proportion of nonmetal binding ligand is a constant value for any test condition. The proportion is not influenced by water chemistry or by metal species. Using the nature of constant proportion, toxicities of metals are well estimated. In addition, the toxic effects of metal mixtures are the simple sum of the toxicities of each metal (additive effect) corresponding to the bioavailable form of the metals. In terms of total concentration of metals in water, however, nonadditive effects, such as antagonism and synergism, are possible.     

The promoting effect of eucommiol from Eucommiae cortex on collagen synthesis

The effect of a methanol extract of Eucommiae Cortex on collagen synthesis was investigated in false aged model rats. Granuloma formation and collagen synthesis were significantly increased by the administration of the methanol extract of Eucommiae Cortex. The effective component of Eucommiae Cortex was then discussed by fractionating the methanol extract of Eucommiae Cortex. Eucommiol, a main component in the water fraction of the methanol extract, was found to be an effective compound. In our previous paper, we reported the promoting effect of Eucommia ulmoides OLIVER leaf on collagen synthesis, and found geniposidic acid and aucubin were the main effective compounds in the leaf. Based on our data in this paper, we clarified that the main effective components of the Eucommia ulmoides OLIVER leaf and Eucommiae Cortex were different. Geniposidic acid and aucubin were reported to be contained at a high concentration in the fresh cortex of Eucommia ulmoides OLIVER, but during the drying process and storage, most of them were destroyed by enzymes in the cortex and very little remained in the Eucommiae Cortex. Therefore, we investigated the effect of the methanol extract of fresh cortex of Eucommia ulmoides OLIVER. A stronger effect than Eucommiae cortex was shown, and geniposidic acid, aucubin and geniposide were concluded to be the main effective components. Although geniposide was found to be an effective compound, when the dose was higher than 50 mg/kg/d, toxicity was shown. The pharmaceutical effect of eucommiol was reported for the first time.