Mumps virus can suppress the effective augmentation of HPC-induced apoptosis by IFN-gamma through disruption of IFN signaling in U937 cells.

Cells of the human promonocytic cell line U937 were found to be sensitive to hexadecylphosphocholine (HPC), which is a potential anticancer drug. Induction of apoptosis was found in U937 cells after treatment with HPC for 24 to 48 hr. The apoptosis in U937 cells exposed to HPC was increased significantly in the presence of interferon-gamma (IFN-gamma). The augmentation of HPC-induced apoptosis by IFN-gamma is repressed in cells (U937-MP) persistently infected with mumps virus. A persistently infected cell line, U937-MP, showed poor induction of signal transducers and activators of transcription-1alpha (STAT-alpha), STAT-2, p48 and IFN-regulatory factor-1 (IRF-1), which are closely correlated with interferon-alpha (IFN-alpha) and IFN-gamma signaling pathways. Expression of MHC class-I or class-II was augmented by IFN-alpha or IFN-gamma in U937 cells, but not in persistently infected cells. Therefore, it is suggested that the IFN-gamma signaling pathway plays an important role in the augmentation of HPC-induced apoptosis. Mumps virus can suppress the IFN-gamma signaling pathway and subsequent development of apoptosis.

Plasma-treated lenowoven polyethylene ribbon for bone fixation at dentoalveolar osteotomy.

Plasma-treated lenowoven polyethylene ribbon was used for splinting between teeth around osteotomy lines in anterior segmental dentoalveolar osteotomy. This fixation was continued for 2 to 3 months, during which there was no damage or fall of the ribbon. In addition, the patients were able to eat their usual food, had much less pain in the teeth and oral mucosa, did not feel uncomfortable in the mouth, had no tooth damage or carious teeth, and had a good aesthetic appearance. In all eight jaws (five patients), accurate and strong bone fixation was achieved based on the planned occlusion. Patient complaints and pain were obviously less with this method than other methods. Polyethylene ribbon is quite useful for bone fixation in anterior segmental dentoalveolar osteotomy.

Augmentation of verotoxin-induced cytotoxicity/apoptosis by interferon is repressed in cells persistently infected with mumps virus.

Verotoxin type 2 (VT2) produced by enterohemorrhagic Escherichia coli (EHEC) has been shown to have high cytotoxic potency toward several human B lymphoid cell lines with and without Epstein-Barr virus (EBV). Cell death, apoptosis induced by VT2, is closely correlated with the expression of receptor molecule Gb3/CD77, recognized by the toxin, but not with the infection or presence of EBV. Pretreatment of cells with interferon-alpha (IFN-alpha) for 24 h resulted in augmentation of apoptosis by VT2. Pretreatment within 8 h, however, was not effective. It has been reported that IFN-alpha-induced apoptosis is correlated with the induction of the 2',5'-OAS/RNase L system or dsRNA-activated protein kinase (PKR) or both. We have established persistent infection in both Akata and P3HR-1 cells with mumps virus. The persistently infected cell lines, P3HR-MP2 and Akata-MP2, showed poor induction of 2',5'-OAS and PKR in response to IFN-alpha. Augmentation of VT2-induced apoptosis by IFN-alpha was not found in the cell lines P3HR-MP2 and Akata-MP2. Therefore, these findings were interpreted to indicate that augmentation of VT2-induced apoptosis by IFN-alpha may be mediated by PKR and the 2',5'-OAS/RNaseL system. It is also suggested that mumps virus can suppress apoptosis and establish persistent infection.

Gene arrangement in the upstream region of Clostridium botulinum type E and Clostridium butyricum BL6340 progenitor toxin genes is different from that of other types.

The cluster of genes encoding the botulinum progenitor toxin and the upstream region including p21 and p47 were divided into three different gene arrangements (class I-III). To determine the gene similarity of the type E neurotoxin (BoNT/E) complex to other types, the gene organization in the upstream region of the nontoxic-nonhemagglutinin gene (ntnh) was investigated in chromosomal DNA from Clostridium botulinum type E strain Iwanai and C. butyricum strain BL6340. The gene cluster of type E progenitor toxin (Iwanai and BL6340) was similar to those of type F and type A (from infant botulism in Japan), but not to those of types A, B, and C. Though genes for the hemagglutinin component and P21 were not discovered, genes encoding P47, NTNH, and BoNT were found in type E strain Iwanai and C. butyricum strain BL6340. However, the genes of ORF-X1 (435 bp) and ORF-X2 (partially sequenced) were present just upstream of that of P47. The orientation of these genes was in inverted direction to that of p47. The gene cluster of type E progenitor toxin (Iwanai and BL6340) is, therefore, a specific arrangement (class IV) among the genes encoding components of the BoNT complex.

Felodipine therapy may not alter glucose and lipid metabolism in hypertensives. Felodipine Multicenter Prospective Study Group in Japan.

The effects of long-term monotherapy with felodipine, a calcium antagonist, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 51 hypertensive patients: 13 with normal glucose tolerance and 38 with glucose intolerance. The levels of plasma glucose, serum lipids, and glycosylated hemoglobin A1c were determined before and during long-term (7.5 +/- 0.5 months; range, 6 to 9 months) therapy with felodipine. A 75-g oral glucose tolerance test was performed before and during long-term felodipine therapy. Significant decreases in both systolic and diastolic blood pressures in both patient groups were maintained during the therapy. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patients with normal glucose tolerance developed diabetes mellitus during the study. Serum lipid levels did not change significantly in either group of patients except for significant decreases in high-density lipoprotein cholesterol and apolipoprotein A-I in the group with normal glucose tolerance tests, but those changes remained within the normal range. Furthermore, neither serum lipid nor apolipoprotein levels were altered, even in patients with hypercholesterolemia (total cholesterol levels, > 5.69 mmol/L = 220 mg/dL). These results suggest that long-term therapy with felodipine may not alter glucose and lipid metabolism in hypertensive patients, and felodipine appears to be useful as an antihypertensive agent for hypertensive patients with either dyslipidemia or impaired glucose metabolism.

[The effect of mexiletine on theophylline pharmacokinetics in patients with bronchial asthma].

Reported side effects of mexiletine, a useful drug for managing premature ventricular contractions (PVC) and ventricular tachycardia (VT), are gastrointestinal symptoms including nausea and vomiting. Theophylline, a bronchodilator, also causes similar gastrointestinal symptoms with its frequency proportional to the increases in its serum concentration. The occurrence of gastrointestinal symptoms is known to increase in combination therapy of mexiletine and theophylline. However, the pharmacokinetic interaction between mexiletine and theophylline has not been clarified. We, therefore, investigated the effects of mexiletine on theophylline pharmacokinetics. Three patients with bronchial asthma complicating PVC and/or VT (one male and 2 females, aged 70.0 +/- 13.1 years) were studied. All patients were given prophylactic theophylline anticipatory for asthmatic attacks, which was followed by oral administration of mexiletine, 200-300 mg daily, for PVC and/or VT. The serum theophylline concentrations in 3 cases were increased from 13.8 to 25.3 micrograms/ml, from 14.6 to 27.8 micrograms/ml, and from 10.4 to 15.4 micrograms/ml, respectively, after the administration of mexiletine. However, significant decreases in theophylline clearance were observed after the administration of mexiletine by 46, 47 and 35%, respectively. (p < 0.05) With a decrease in theophylline dosage, the serum theophylline concentrations decreased, and gastrointestinal symptoms resolved. Theophylline is metabolized mainly in the liver through an oxidative reaction of p-450 enzyme, however, its metabolism is affected by many factors, such as medications and complications. The results of this study indicated that mexiletine decreases the theophylline clearance by inhibiting the p-450 oxidative reaction to theophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative study of amino acid composition in an extract from hornet venom sacs: high content of neuroactive amino acids in Vespa.

The amino acid compositions of extracts from the venom sacs of Vespa mandarinia, V. xanthoptera, V. tropica, V. analis and Vespula lewisi were analyzed. omega-Amino acids, which are inhibitory neurotransmitters, such as gamma-amino-n-butyric acid, taurine, beta-alanine and glycine, were predominant components in Vespa, but a minor component in Vespula. Glutamic acid, an aminergic excitatory neurotransmitter, was present in large quantities. Leucine, an insect autotoxin, was detected. Arginine was found in all the venoms and glutamine was also abundant. Tryptophan and histidine, precursors of serotonin and histamine, respectively, were also found. Thus, neuroactive amino acids that may exert inhibitory effects on insects neuronal axons and neuromuscular junctions were present in large amounts, and may facilitate paralysis of insect prey.