Seroprevalence survey on measles, mumps, rubella and varicella antibodies in healthcare workers in Japan: sex, age, occupational-related differences and vaccine efficacy.

A seroprevalence survey on measles, mumps, rubella and varicella was conducted on healthcare workers (HCWs) at Shimane University Hospital, Japan utilizing an enzyme immunoassay. Of 1811 HCWs tested, 91.8% were seropositive to measles, 92.1% to mumps, 89.5% to rubella and 96.3% to varicella. Sex-related differences in seroprevalence were found in rubella (males vs. females: 84.7 vs. 92.2%, P < 0.001). Moreover, males aged 30-39 years were most susceptible to rubella (22.4%), which may be attributed to the design of childhood immunization programmes in Japan. Individuals aged ≤ 29 years were more susceptible to measles (14.3%) and mumps (10.9%), compared to other age groups. There were no significant sex- and age-related differences in varicella seroprevalence. The physician occupational group was more susceptible to rubella, but no significant occupational-related difference was observed in the other diseases. Susceptible subjects, with negative or equivocal serological results were given a vaccine which induced seroconversion in most vaccinees. Seroconversion occurred more frequently in the equivocal group than in the negative group. These findings provide a new insight for the seroprevalence survey of vaccine-preventable diseases in Japanese HCWs with special reference to vaccine efficacy.

Relationship between buccal mucosa ridging and viscoelastic behaviour of oral mucosa.

The aim of this study was to clarify the relationship between the buccal mucosa ridging (BMR), which has been mentioned to be a clinical sign of clenching, and the viscoelastic behaviour of oral mucosa. Twenty-three people with BMR and 21 people without BMR participated as volunteers in this study. Measurements of viscoelastic behaviour were performed using a suction viscoelastic meter on central part of lower labial mucosa. A suction pressure of 300 hPa was applied for 2 s and then released for 2 s, and the time-dependent changes in the deformation of the mucosa over this 4 s were recorded as a deformation curve. Distensibility, remaining deformation and elastic recovery, which describe viscoelastic behaviour, were calculated by the deformation curve. These parameters were compared between groups with and without BMR. No significant difference was found in distensibility between the two groups (P=0·349). There were significant differences for the remaining deformation (P=0·012) and the elastic recovery (P=0·032), and the group with BMR showed higher remaining deformation and lower elastic recovery than the group without BMR. Based on these results, it clarified that the BMR is related to the mucosal viscoelastic behaviour, in particular remaining deformation and elastic recovery.

Anaerobic degradation of palm oil mill effluent (POME).

The biodegradation characteristics of palm oil mill effluent (POME) and the related microbial community were studied in both actual sequential anaerobic ponds in Malaysia and enrichment cultures. The significant degradation of the POME was observed in the second pond, in which the temperature was 35-37 °C. In this pond, biodegradation of major long chain fatty acids (LCFA), such as palmitic acid (C16:0) and oleic acid (C18:1), was also confirmed. The enrichment culture experiment was conducted with different feeding substrates, i.e. POME, C16:0 and C18:1, at 35 °C. Good recovery of methane indicated biodegradation of feeds in the POME and C16:0 enrichments. The methane production rate of the C18:1 enrichment was slower than other substrates and inhibition of methanogenesis was frequently observed. Denaturing gradient gel electrophoresis (DGGE) analyses indicated the existence of LCFA-degrading bacteria, such as the genus Syntrophus and Syntorophomonas, in all enrichment cultures operated at 35 °C. Anaerobic degradation of the POME under mesophilic conditions was stably processed as compared with thermophilic conditions.

Electromagnons in the spin collinear state of a triangular lattice antiferromagnet.

Terahertz time-domain spectroscopy was performed to directly probe the low-energy (1-5 meV) electrodynamics of triangular lattice antiferromagnets CuFe(1-x)Ga(x)O2 (x=0.00, 0.01, and 0.035). We discovered an electromagnon (electric-field-active magnon) excitation at 2.3 meV in the paraelectric ↑↑↓↓ collinear magnetic phase, while this electromagnon vanishes in the ferroelectric helimagnetic phase. Anticorrelation with noncollinear magnetism excludes the exchange-striction mechanism as the origin of dynamical magnetoelectric coupling, and hence evidences the observation of a spin-orbit coupling mediated electromagnon in the present compound.

Optical probe for anomalous Hall resonance in ferromagnets with spin chirality.

We have investigated the infrared optical Hall conductivity, sigma(xy)(omega) for band-filling-controlled ferromagnetic crystals of Nd2Mo2O7, revealing the dynamical properties of their anomalous Hall effect (AHE). A resonant structure and its systematic filling dependence were observed in the Hall conductivity spectra in the midinfrared region (typically at 0.1 eV), while similar effects were not discerned in the diagonal (longitudinal or ordinary) conductivity spectra. This property of sigma(xy)(omega) provides crucial and essential information to understand the microscopic mechanism of AHE including its dc limit. Specifically, the interband transition at the magnetic-monopole-like band-anticrossing point, which is split by spin chirality, is the dominant source in AHE.

A new case of abnormal insulinemia with diabetes. Reduced insulin values determined by radioreceptor assay.

A 44-yr-old Japanese woman was found to have diabetes with marked fasting hyperinsulinemia. Her fasting plasma glucose, serum insulin, and C-peptide levels were 137 mg/dl, 204 microU/ml, and 1.13 pmol/ml, respectively, and the C-peptide-to-insulin molar ratio was markedly reduced. Insulin antibodies and insulin-receptor antibodies were negative. Fasting levels of counter-insulin hormones were normal. She had normal hypoglycemic response to exogenous insulin injection. Binding of 125I-labeled insulin to erythrocytes was normal. Oral glucose-tolerance tests in eight members of her first-degree relatives revealed four members (mother, sister, brother, and daughter) with fasting hyperinsulinemia (111-314 microU/ml), and two of them (mother and sister) were overtly diabetic. Thus, the abnormality was thought to be an autosomal dominant trait. Reverse-phase high-performance liquid chromatograph analysis of immunopurified insulin obtained from her serum revealed two peaks of insulin immunoreactivity. The amount of the abnormal insulin peak was seven times greater than that of normal insulin. The abnormal insulin was eluted after bovine, human, and porcine insulins, indicating it has a more hydrophobic nature than normal human insulin. Radioreceptor assay (RRA) for serum insulin with guinea pig kidney membrane revealed that the binding activity of their serum insulin was markedly decreased. Discrepancies between the values measured by RRA and those measured by radioimmunoassay were also found in her family members with hyperinsulinemia but not in her family members without hyperinsulinemia and other hyperinsulinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

IFN-alpha enhances TNF-alpha-induced apoptosis through down-regulation of c-Myc protein expression in HL-60 cells.

We examined the effect of interferon-alpha (IFN-alpha) in combination with tumor necrosis factor-a (TNF-alpha) on growth, differentiation and apoptosis in HL-60 human myeloid leukemia cells. IFN-alpha inhibited cell growth and induced apoptosis, but not differentiation, in HL-60 cells. IFN-alpha enhanced TNF-alpha-induced apoptosis. We also investigated the expression of c-Myc and Bcl-2 oncoproteins, which are implicated in the survival or death of a cell. The levels of c-Myc protein expression were not changed by IFN-alpha alone at 24hrs of treatment, but were down-regulated at 72 hrs, accompanied by the appearance of apoptotic cells. While, IFN-alpha did not affect the level of Bcl-2 protein expression during this cultivation time. Interestingly, a combination treatment of IFN-alpha with TNF-alpha showed a greater decrease of c-Myc expression than TNF-a alone at 24hrs. Whereas, IFN-alpha did not significantly modulate Bcl-2 expression levels which were down-regulated by TNF-alpha. Therefore, the enhancement of TNF-alpha-induced apoptosis by IFN-a might be closely associated with the greater down-regulation of c-Myc protein, rather than Bcl-2. In contrast, with rapid down-regulation of c-Myc expression caused by TNF-alpha, IFN-alpha down-regulated c-Myc rather late (at 72 hrs), suggesting that both cytokines have a distinct pathway regulating c-Myc protein expression. However, the enhancement of apoptosis in the combination treatment would suggest the presence of a common signaling pathway for induction of apoptosis at down-stream of c-Myc.

Effect of new oral antidiabetic agent CS-045 on glucose tolerance and insulin secretion in patients with NIDDM.

OBJECTIVE: To study the effects of CS-045, a newly developed thiazolidine analogue, on glucose tolerance and insulin response to oral glucose load in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Nineteen NIDDM patients (mean +/- SD age 48.9 +/- 9.4 yr) whose previous glycemic control on diet and/or sulfonylurea (SU) therapy was judged stable but unsatisfactory (greater than 7.8 mM) were selected for this study. CS-045 (400 mg/day p.o.) was given alone or together with the previous SU drugs for 12 wk. A 75-g oral glucose tolerance test (OGTT) was performed before and after CS-045 treatment. RESULTS: The following results were found after CS-045 treatment. 1) Fasting plasma glucose (FPG) and HbA1c decreased (n = 19, FPG, 11.0 +/- 2.4 vs. 8.4 +/- 2.7 mM [before vs. after], P less than 0.001; HbA1c, 8.0 +/- 1.1 vs. 7.4 +/- 1.3%, P less than 0.005), and glucose tolerance markedly improved. 2) Fasting insulin (immunoreactive insulin [IRI]) and insulin response during OGTT decreased (n = 19, fasting IRI, 77.4 +/- 49.8 vs. 56.5 +/- 24.6 pM [before vs. after], P less than 0.05; area under the curve of IRI, 540.3 +/- 350.5 vs. 426.4 +/- 216.3 pM.h, P less than 0.05). CONCLUSIONS: CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.

Studies on cardiovascular agents. 6. Synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to heterocyclic systems.

The synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to pyrrole, thiophene, pyran, pyridine, and pyridazine are described. Among these compounds, 8-tert-butyl-7,8-dihydro-5-methyl-6H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine (23) was found to be the most promising potential cardiovascular agent, having been shown to be more potent in coronary vasodilating activity than trapidil [7-diethylamino)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine] and approximately equipotent to guanethidine sulfate in antihypertensive activity.

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.

Nature of kininase activity in the exudate in kaolin-induced inflammation of the air pouch type in rats.

Experimental inflammation was induced by injection of a suspension of kaolin in carboxymethylcellulose solution into a subcutaneous air pouch preformed on the back of rats. Endogenous bradykinin generated in the inflammatory pouch declined quickly unless kininase inhibitors were administered into the pouch. Bradykinin injected into the pouch brought about no significant increase in plasma exudation in the pouch unless kininase inhibitors were administered simultaneously. Although kininase I and II activities were present in normal rat serum, kininase II rather than kininase I was mainly responsible for the degradation of bradykinin in rat serum. In the pouch challenged with the kaolin suspension and vehicle, kininase II originating from the pouch wall tissue played a predominant role in the degradation of bradykinin while the role of kininases derived from the blood and inflammatory cells was minor.

Effect of bromelain on kaolin-induced inflammation in rats.

The effects of stem bromelain on the plasma kallikrein system, bradykinin levels and plasma exudation at the inflammatory site were examined in rats with a kaolin-induced inflammation of an air pouch. Bromelain (5, 7.5 mg/kg) caused a dose-dependent decrease of bradykinin levels at the inflammatory site and a parallel decrease of the prekallikrein levels in sera. Plasma exudation was also reduced dose dependently. Bradykinin-degrading activity in sera was elevated after treatment with bromelain, although it was unchanged in the pouch fluid. These data indicate that bromelain inhibits plasma exudation through inhibiting the generation of bradykinin at the inflammatory site via depletion of the plasma kallikrein system.

C-Myc and Bcl-2 protein expression during the induction of apoptosis and differentiation in TNF alpha-treated HL-60 cells.

We examined c-Myc and Bcl-2 protein expressions during the induction of apoptosis and differentiation in TNF alpha-treated HL-60 cells using a two-color flow cytometric method. We found that c-Myc protein was rapidly down-regulated in the apoptotic cells while Bcl-2 protein was expressed at relatively high levels. Concomitantly with terminal differentiation Bcl-2 protein was down-regulated in differentiating cells as well as c-Myc protein. We also showed that c-myc antisense oligonucleotides could induce apoptosis in HL-60 cells whereas bcl-2 antisense did not induce apoptosis during the early time of treatment. These results suggest that the down-regulation of c-Myc protein expression is a primary event to induce apoptosis and neither consistent expression of c-Myc protein nor rapid down-regulation of Bcl-2 protein is necessary for the initial processing of apoptosis in HL-60 cells. Furthermore, concomitant down-regulation of c-Myc and Bcl-2 is closely associated with terminal differentiation and apoptotic cell death of HL-60 cells treated with TNF alpha.

Cell cycle-independent down-regulation of BCL-2 protein expression in differentiating HL-60 cells.

To understand the relationship between bcl-2 protein expression and the cell cycle during the processes of differentiation, we examined bcl-2 protein levels expressed during cell cycle phases in differentiating HL-60 human leukemia cells by using a two-color flow cytometric method. In exponentially proliferating HL-60 cells bcl-2 protein was constitutively expressed throughout the cell cycle phases, but a small population of G0/G1 cells expressed decreased levels of protein as compared with other cell cycle phases. HL-60 cells can be induced to differentiate to granulocytic pathway by retinoic acid or dimethylsulfoxide, and to monocytic/macrophagic pathway by 1, 25 dihydroxyvitamin D3 or 12-O-tetradecanoylphorbol -13-acetate. During treatment with any of these inducing agents, bcl-2 protein expression was time-dependently down-regulated after 24 h. A two-color flow cytometric analysis revealed that this down-regulation occurred throughout cell cycle phases, indicating that bcl-2 protein expression was down-regulated in cell cycle-independent manner during induction of differentiation in HL-60 cells. To our knowledge, this is the first demonstration suggesting that the regulation of bcl-2 protein expression is not related to the cell cycle during induction of differentiation in HL-60 cells.

c-myc protein expression during cell cycle phases in differentiating HL-60 cells.

We examined c-myc protein expression in cell cycle phases during differentiation induction of HL-60 cells by flow cytometry using an indirect immunofluorescence method. In exponentially proliferating HL-60 cells, c-myc protein was expressed in a cell cycle dependent manner. During the differentiation induction of HL-60 cells with dimethylsulfoxide (DMSO), c-myc protein was rapidly down-regulated in the G1/0 specific phase prior to the appearance of differentiation associated markers. Our results indicate that c-myc protein functions in the G1/0 specific phase in cellular differentiation, and the rapid down-regulation of c-myc protein in G1/0 phase is closely associated with initial differentiation programs.

Elevated ratio of summed serum proinsulin to insulin response after oral glucose load in type 2 diabetes decreases following sulfonylurea treatment.

We showed previously that the disproportionate elevation of serum proinsulin at fasting and after glucose ingestion in Type 2 diabetes is reduced to nearly normal after improvement of glycemic control by diet therapy. In this study, we investigated the effect of sulfonylurea (SU) treatment on serum proinsulin levels and proinsulin/insulin ratio (PI/I) during oral glucose tolerance test in patients with Type 2 diabetes. Thirteen diabetic patients (age 56 +/- 9 years, body mass index 22.4 +/- 1.9 kg/m2, mean +/- SD) were examined by 75 g oral glucose tolerance test (OGTT) before and after glycemic control by SU therapy. Mean interval of two OGTTs was 126 days. Serum proinsulin was measured by the radioimmunoassay using a human proinsulin-specific antiserum. When glycemic control improved after SU therapy (mean fasting plasma glucose 11.5 and 6.0 mmol/l, before and after SU treatment), fasting insulin, proinsulin and PI/I ratio did not change significantly. Insulin response during OGTT markedly increased after SU therapy. Summed value of insulin (sigma I) increased from 634 to 1064 pmol/l after SU (P < 0.01), whereas summed proinsulin (sigma PI) did not change significantly (146 and 159 pmol/l), resulting in a significant decrease in sigma PI/sigma I (23.6-15.1%, P < 0.05). We conclude that the disproportionate elevation of proinsulin during OGTT in patients with Type 2 diabetes can be reduced after glycemic control by SU treatment, chiefly by a selective increase in insulin response.

Effect of islet amyloid polypeptide (IAPP/amylin) on 2-deoxyglucose uptake in mouse pancreatic acini.

In order to examine the effect of islet amyloid polypeptide (IAPP/amylin), a product of the pancreatic beta cell and a major component of islet amyloid deposits, on exocrine pancreatic function, we studied the effect of rat IAPP amide (IAPP-NH2) on 2-deoxy-D-glucose (2-DG) uptake in isolated mouse pancreatic acini. Mouse pancreatic acini were preincubated for 80 min with various concentrations of IAPP-NH2 (1 nM-1 microM) and [3H]2-DG uptake for 20 min was measured. The full effect of IAPP-NH2 on this function was not immediate but increased linearly with time for up to 80 min of incubation. IAPP-NH2 caused a dose-dependent stimulation of 2-DG uptake by mouse acini; a detectable effect at 10 nM and a maximal effect at 1 microM. In the presence of 1 microM IAPP-NH2, 2-DG uptake increased by 69 +/- 8% above basal (mean +/- SD, n = 6). The results indicate that IAPP-NH2 stimulates glucose uptake in mouse pancreatic acini, and raise the possibility that IAPP-NH2 plays some physiological role in the insuloacinar axis in mouse pancreas.

HLA DR antigens in adult-onset and juvenile-onset Japanese insulin-dependent diabetic patients.

In order to discover the HLA DR antigens linked to Japanese insulin-dependent diabetes (IDDM), and to relate them to the clinical features, HLA DR antigens were examined in 75 IDDM patients including 56 adult-onset cases. Among the tested HLA DR antigens, 4, w9 and w13 were significantly more frequent in IDDM (55%, 47% and 27% respectively). The relative risk was 1.71 for DR4, 2.81 for DRw9 and 4.74 for DRw13. DR2 was significantly less frequent and the relative risk was 0.14. The distribution of DR antigens did not differ between juvenile-onset and adult-onset IDDM, males and females, or cases with and without thyroid autoantibodies. Homozygotes for DRw9 were, but those for DRw13 and DR4 were not more frequent than expected by a random combination. Heterozygotes for DR4 and w9 were less frequent while other heterozygotes for high-risk antigens were as frequent as expected. 97% of IDDM had either DR4, w9 or w13. In conclusion, HLA DR4, w9 and w13 were significantly increased in patients with both juvenile- and adult-onset IDDM. There was no surplus increase in the frequency of IDDM patients with two high-risk HLA DR antigens, more than expected from random combination of each of these DR antigens. Clinical features did not differ among IDDM patients with each of these three antigens.