C and V proteins of Sendai virus target signaling pathways leading to IRF-3 activation for the negative regulation of interferon-beta production

We here report a molecular basis for downregulation of interferon (IFN)-beta production by V and C proteins of Sendai virus (SeV). The infection of HeLa cells with SeV poorly induced IFN-beta even if the expression of C/C' was disrupted. In contrast, when the expression of C/C'/Y1/Y2 or V/W was disrupted, SeV infection strongly induced IFN-beta production and significantly activated the interferon regulatory factor (IRF)-3 pathway. The independent expression of C or V inhibited the double-stranded (ds) RNA- or Newcastle disease virus (NDV)-induced activation of IRF-3 and NF-kappa B, as well as the IFN-beta promoter. This inhibitory effect was also observed when Y1, Y2, or a C-terminal half fragment (aa 85-204) of C was independently expressed. Phosphorylation and homodimer formation of IRF-3 were suppressed not only in cells infected with SeV capable of expressing both C/C'/Y1/Y2 (or Y1/Y2) and V/W, but also in HeLa cells constitutively expressing Y1. These results suggest that C, Y1, Y2, and V block signaling pathways leading to IRF-3 activation to downregulate IFN-beta production.     

Oxygen radical production by neutrophils from patients with bacterial infection and rheumatoid arthritis

The production of three kinds of oxygen radicals (superoxide, hydrogen peroxide, and hydroxyl radicals) by neutrophils from patients with bacterial infection or rheumatoid arthritis was measured. The stimulators used in this study were opsonized zymosan (1 mg/ml), phorbol myristate acetate (20 ng/ml), A23187 (1M, and platelet activating factor (1M). Oxygen radical production by neutrophils from patients with rheumatoid arthritis was not significantly different from that of the control group. Hydrogen peroxide production by the neutrophils from patients with bacterial infection was significantly enhanced by only opsonized zymosan, but the production of the other kinds of oxygen radicals was not. Cytochalasin B reduced the production of hydrogen peroxide induced by opsonized zymosan more markedly than that of any other kind of oxygen radical. The measurement of hydrogen peroxide is suggested to be the most accurate indicator of the enhancement of intracellular production of oxygen radicals by neutrophils during infection.     

Practical application of nutritional assessment protein and inflammatory marker in the nutrition support team (NST)

Recently nutrition support team (NST) has been established for the purpose of prevention of complications which are caused by nutrition disorders and reduction of the medical expenses. Although physical examinations and blood biochemical data had been used as the indexes evaluating nutritional of patients, they were not suitable for the evaluation for the short-term in-patient. On the contrary, serum albumin (ALB) has been wildly used as a nutritional marker. However, it is impossible to evaluate nutrition state for the short-term in-patient and acute phase disease patient accurately, because the plasma half-life is 21 days and it takes long time to detect the change in nutritional state by its value. Rapid turnover proteins (RTP), whose plasma half-life is shorter, has paid attention to evaluate nutritional state for the short-term in-patients and acute phase disease patients. Although, prognostic inflammatory and nutritional index (PINI) was considered as a useful maker for evaluating inflammatory and nutritional states using the concentrations of transthyretin (TTR), a RTP, alpha1-acid glycoprotein (alpha1-AG), a chronic inflammation marker, C reactive protein (CRP), a acute inflammation marker, and ALB, However, it has several pitfalls. We newly made serum amyloid A (SAA) index using SAA instead of CRP. When we compared SAA index with PINI in many diseases, it turned out that SAA index became a more effective index which reflected the patient condition than did PINI. As for this index, it is expected to be used by NST while further alternation may be needed.     

Pseudomonas aeruginosa

We investigated the causes of nosocomial infection of P. aeruginosa in a recent outbreak of P. aeruginosa in our hospital. Multi-drug-resistant-P. aeruginosa(MDRPS) that did not produce class B beta-lactamase was isolated from 20(40.0%) patients, occurring in 50 patients hospitalized in the Internal Medicine Ward E in our hospital in 1999 was investigated. All of the patients had brain-vesicular damage as the underlying disease, and 12 patients had been fed by nasal feeding or through a gastric stoma. MDRPS was isolated from sputum(7), urine samples(8), wound discharge(4) and 1 catheter. The bacteria were resistant to piperacillin, ceftazidime, sulbactam/cefoperazone, minocycline and ofloxacin, and in 40% the MIC of the imipenem was more than 8 micrograms/ml. We did not detect MDRPS in any equipment parts or waste water, including the sink in Ward E, but it was detected in the nutrient fluid for nasal feeding and in the line of one patient. The DNA homology of MDRPS isolated from the patient and the nutritive liquid was the same as that of some strains isolated in Ward E, as shown by random amplified DNA polymorphism PCR. In conclusion, we speculated that some nosocomial infections due to MDRPS resistant to imipenem were caused by contaminated nasal feeding.     

Late onset type I familial amyloidotic polyneuropathy: Presentation of three autopsy cases in comparison with 19 autopsy cases of the ordinary type

Clinicopathological features of three autopsy cases of extremely rare late onset type I familial amyloldotic polyneuropathy were presented and compared with 19 autopsy cases of the ordinary type. In the late onset cases, the ages at onset and at death were 27.5 and 24.5 years older, respectively, compared with the ordinary type. Also, duration of the total clinical course form onset to death was 3.7 years less than in the late onset cases. The degree of amyloid deposition was more marked in the heart of the late onset cases, causing prominent cardiac hypertrophy. It was also marked In the kidneys or thyroid of two cases, but slight to moderate in the peripheral or autonomic nervous tissues in all cases. Immunohistochemical Investigation demonstrated the presence of transthyretin (TTR) as an amyloid precursor protein and of serum amyloid P-component in amyloid deposits in various organs and tissues of the late onset type. These findings, as well as serum levels of variant TTR, were similar to those of the ordinary type. These results suggest that there are some factors other than the amyloid precursor protein that effect the degree of amyloid deposition.     

The numerical aberrations of chromosome 7 detected by fluorescence in situ hybridization in human breast cancers

The relationship between the numerical aberrations of chromosome 7 in interphase cells and the clinicopathological behavior of breast tumors was investigated in 51 touch imprinted preparations of breast tumors. Using fluorescence in situ hybridization with a chromosome 7-specific DNA probe, the fluoresceinisothiocyanate (FITC) spots mean and the representative copy number of each breast tumor were examined. The FITC spots mean (2.34) of 40 breast cancers increased compared with that of 11 benign lesions (1.98) (P < 0.02). The FITC spots mean tended to increase with the advancing stage and tumor size of the breast cancer. The FITC spots mean in the case with metastasis was also of a higher value than that without metastasis (P < 0.01). Furthermore, the existence of trisomy or over-trisomy of the copy number was related to the advancing stage and tumor size (P < 0.05 and P < 0.01, respectively). These findings suggest that the FITC spots mean and polysomy of the number of chromosome 7 may be highly predictive for breast tumor aggressiveness.     

Myocardial changes after infection with Coxsackie virus B3 in nude mice.

Athymic BALB/c-nu/nu (nu/nu) mice were inoculated i.p. with Coxsackie virus B3. The infected nu/nu mice were studied histopathologically, virologically and serologically in comparison with BALB/c-nu/+ (nu/+), BALB/c-+/+(+/+) and conventional ddY/S mice inoculated with the same virus. The virus titre in the hearts of nu/nu mice was roughly similar to that of nu/+ or +/+ and was higher than that of ddY/S. The neutralizing antibody titre in nu/nu mice was slightly lower than that of nu/+ or +/+ mice and somewhat lower than that of ddY/S mice. Histopathologically, there was a lack of mononuclear cells in myocarditis produced by Coxsackie virus B3 in athymic nu/nu mice. In contrast, myocarditis with mononuclear cell infiltrations were found in nu/+, +/+ and ddY/S mice. The lack of mononuclear cell reaction was a distinguishing difference in the myocardial changes of athymic nu/nu mice from those in nu/+, +/+ and ddY/S mice. The incidence in the myocardial lesions of nu/nu mice was about the same as those in nu/+, +/+ and ddY/S mice. However, the intensity of the myocardial changes of nu/nu mice was significantly less than that of other three groups. From the histopathological viewpoint, it is suggested that inflammatory response in the myocardium of mice infected with Coxsackie virus B3 is thymus-dependent.     

Induced circular dichroism of biphenyl and its derivatives in mesophase

The mesophase induced circular dichroism (CD) of biphenyl and its derivatives was investigated using the Tween 80 (monooleate of the ether of sorbitan with 4 mol of polyethyleneglycol)-water system, which can form a twisted smectic mesophase. The sign of CD bands in this mesophase is explained by a modified C₂-symmetry rule, since it can be considered that alignment of the solute molecules in this mesophase can be elucidated in terms of a pseudo-C₂ symmetry, when the concentration of the solute is comparatively high. The assignments of the electronic transitions of the solute molecules show a good accordance with results of magnetic circular dichroism study.