Health-related QOL of elderly patients with pulmonary M. avium complex disease in a university hospital.

BACKGROUND: Little is known about the clinical characteristics and health-related quality of life (HQOL) of elderly patients with pulmonary Mycobacterium avium complex (pMAC) disease. OBJECTIVES: To evaluate HQOL using the 36-Item Short-Form Health Survey and St George's Respiratory Questionnaire (SGRQ) and to investigate the predictors of HQOL changes among elderly patients with pMAC disease. METHODS: This prospective cohort registry was conducted at Keio University Hospital, Tokyo, Japan, between May 2012 and July 2015 and included 84 patients with pMAC disease aged 75 years who had completed the HQOL questionnaire and 48 patients with pMAC disease who had been followed up and completed the HQOL questionnaire in cross-sectional and longitudinal analyses, respectively. RESULTS: In cross-sectional analyses, elderly patients with pMAC disease had significantly lower role-physical, general health, vitality, social functioning, role-emotional and role/social component scores than the general Japanese elderly population. Analysis of covariance revealed that patients with cavitary lesions had significantly worse physical functioning and SGRQ scores (P < 0.05). Longitudinal analysis showed that under-treatment, short duration of disease and positive sputum smear at baseline were predictors of worse HQOL at 12 months. CONCLUSIONS: Elderly patients with pMAC disease have reduced HQOL. Further large studies on HQOL are required to refine the use of this parameter in the treatment of these patients.

Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice.

We have recently found that the combination of ovariectomy (OVX) and chronic restraint stress (CS) causes hippocampal pyramidal cell loss and cognitive dysfunction in female rats and that estrogen replacement prevents the OVX/CS-induced morphological and behavioral changes. In this study, to clarify the mechanisms underlying the OVX/CS-mediated memory impairment further, we examined the roles of cholinergic systems in the OVX/CS-induced memory impairment in mice. Female Slc:ICR strain mice were randomly divided into two groups: OVX and sham-operated groups. Two weeks after the operation, the mice of each group were further assigned to CS (6 h/day) or non-stress group. Following the 3-week-stress period, all mice were subjected to contextual fear conditioning, and context- and tone-dependent memory tests were conducted 1 or 24 h after the conditioning. Overburden with 3 weeks of CS from 2 weeks after OVX impaired context- and tone-dependent freezing and the OVX/CS caused significant Nissl-stained neuron-like cell loss in the hippocampal CA3 region, although OVX and CS alone did not cause such behavioral and histological changes. Replacement of 17ß-estradiol for 5 weeks after OVX suppressed OVX/CS-induced memory impairment and hippocampal Nissl-positive cell loss. Furthermore, the OVX/CS mice exhibited a significant decrease in choline acetyltransferase in the hippocampus compared with other groups. The cholinesterase inhibitors donepezil and galantamine ameliorated OVX/CS-induced memory impairment. These data suggest that cholinergic dysfunction may be involved in the OVX/CS-induced conditioned fear memory impairment. Overall, our findings suggest that the OVX/CS mouse model is useful to study the mechanisms underlying estrogen loss-induced memory deficits.

Ginkgo biloba extract EGb 761 attenuates hippocampal neuronal loss and cognitive dysfunction resulting from chronic restraint stress in ovariectomized rats.

We have recently found that a combination of ovariectomy (OVX) and chronic restraint stress causes cognitive dysfunction and reduces hippocampal CA3 neurons in female rats and that estrogen replacement suppresses the OVX/stress-induced behavioral and morphological changes. In this study, we examined the effect of Ginkgo biloba extract (EGb 761), a popular herbal supplement, on the cognitive dysfunction and neuromorphological change in OVX/stress-subjected rats. Female Fisher 344 rats were randomly divided into three groups: vehicle-treated OVX, EGb 761 (50 mg/kg) -treated OVX and vehicle-treated sham-operated control groups. Two months after ovariectomy, all animals received restraint stress for 21 days (6 h/day), and were then subjected to a novel object recognition test followed by morphological examination by Nissl staining. EGb 761 was orally administered once daily until the behavioral analysis was done. Treatment with EGb 761 improved memory impairment and neuronal loss of hippocampus in the OVX/stress-subjected group in the same ways as 17beta-estradiol. On the other hand, EGb 761 did not affect the loss of bone mineral density and increase in body weight after OVX, although 17beta-estradiol attenuated them. These results have important implications for neuroprotective and cognition enhancing effects of EGb 761 in postmenopausal women and suggest that the effects are mediated by a different mechanism from estrogen.

17beta-estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats.

Several lines of evidence suggest that hormonal changes after menopause may play an important role in the incidence of cognitive dysfunction, and also in the development of Alzheimer's disease. In this study, we investigated the effect of estrogen on cognitive function in rats under different stress environment. Female rats were divided into four groups: two groups were ovariectomized (OVX) and two were sham-operated. One group each of OVX and sham rats was kept in a normal environment, and the other groups were assigned to a daily restraint stress (6 h/day) for 21 days from 2 months after the operation. Following the stress period, subjects were tested for performance in novel object recognition test and then used for morphological and neurochemical analyses. The OVX plus stress (OVX/stress) group showed a significant impairment of recognition of novel objects, compared with the other groups. The OVX/stress group also showed a marked decrease in the number of pyramidal cells of the CA3 region and levels of brain-derived neurotrophic factor mRNA in the hippocampus. We further examined the effect of estrogen against cognitive dysfunction and hippocampal changes of OVX/stress rats. Vehicle or 17beta-estradiol (E2) at 20 microg/day was s.c. administered to OVX/stress rats from 2 days before the stress period to the end of behavioral analysis through an implantable osmotic pump. Chronic E2 treatment decreased stress response and improved the cognitive and morphological impairments relative to vehicle group. These data have important implications for cognition enhancing effect of estrogen treatment in postmenopausal women.

Repetitive monomorphic ventricular tachycardia of left coronary cusp origin.

Repetitive monomorphic ventricular tachycardia with a morphology of inferior axis and left bundle branch block pattern in patients without structural heart disease commonly originates from the right ventricular outflow tract. We report the case of a 22-year-old man with an incessant, monomorphic ventricular tachycardia with a similar morphology originating from the left coronary cusp, which was confirmed by perfect pace mapping, local ventricular activation preceding the onset of QRS by 25 mse, and eliminated by a single delivery of low-energy (11 W) radiofrequency currents.

Initial predictors of survival in patients with systemic sclerosis (scleroderma).

We conducted a retrospective study of 86 patients with systemic sclerosis (SSc) to clarify the initial predictors of survival at the first visit to the hospital. A life-table analysis of survival was performed concerning 137 items from their histories, physical examinations, and laboratory data. The observed cumulative survival rates were 78.0 percent at 5 years and 68.2 percent at 10 years. Ten items were found to be the initial predictors of survival in patients with SSc. Of these 10 items, 9 items showed significant differences within 5 years of the first visit to the hospital. Patients with resting electrocardiographic abnormalities, such as atrial or ventricular arrhythmias, or conduction disturbances, pulmonary fibrosis on the chest x-ray films, or decreased vital capacity had significantly lower survival rates. However, patients with anti-centromere antibody had a significantly better survival rate. In addition, males, aged patients over 65 years old, and patients with proteinuria, leucopenia, or hypergammaglobulinemia had significantly lower survival rates. Only patients with proximal scleroderma at the first visit to the hospital had a significantly lower survival rate after 8 years. These results are useful in predicting individual patients at risk of shortened survival and in managing these patients.

Specificity of antibodies to single-stranded (ss) DNA in SLE patients with anti-phospholipid syndrome.

Although the concept of anti-phospholipid syndrome has been proposed in patients with SLE and other rheumatic diseases, the immunological mechanism is still controversial. Recently, the crossreactivity between anti-cardiolipin antibody and anti-ssDNA antibodies has been discussed in relation to this syndrome. In the present study, the specificity such as the avidity and the crossreactivity of anti-ssDNA antibodies was examined to find a clue to clarify the question why all of anti-cardiolipin antibody positive patients do not have any specific clinical features, thrombosis and spontaneous abortion. The avidity of IgG anti-ssDNA antibodies was examined by salt elution studies in solid phase ELISA. The avidity of anti-ssDNA antibodies tended to be lower in 10 patients with specific features than in other 10 patients without those features. The crossreactivity of affinity purified IgG anti-ssDNA antibodies was investigated by competitive ELISA. Purified anti-ssDNA antibodies from 4 patients without specific features were slightly inhibited by negatively charged phospholipids, cardiolipin and phosphatidylserine, whereas purified anti-ssDNA antibodies from 2 patients with specific features, who were considered to have anti-phospholipid syndrome, were little inhibited by these phospholipids. The above results suggest that the specificity of anti-ssDNA antibodies appears, at least partly, in different manners whether specific features are present or absent in anti-cardiolipin antibody positive patients. Moreover, anti-ssDNA antibodies and anti-phospholipid antibodies may form separate groups of antibodies in patients with anti-phospholipid syndrome.

Production and characterization of monoclonal antibodies to Fc gamma 2a-binding protein isolated from the detergent lysate of a murine macrophagelike cell line, P388D1.

Hybridoma cell lines were produced by fusion of SP2/0 murine myeloma cell line with the spleen cells of Wister rats which were immunized with IgG2a-binding protein isolated from the detergent lysate of a murine macrophagelike cell line, P388D1, by affinity chromatography on IgG-Sepharose 4B. A monoclonal clone (designated as 3A2) out of a total of 13 different antibody-secreting cell lines was found to secrete IgG1 class antibodies, which inhibited more than 70% of the binding of radio-iodinated myeloma IgG2a protein to P388D1 cells. The 3A2 Fab fragments bound specifically to P388D1 cells at 4 degrees C with a KD of 1.9 x 10(-8) M and Bmax of 2.9 x 10(5) per cell. This Fab fragment also specifically bound to Fc gamma 2a receptor (R)-positive T cell line (S49) with a KD of 4.4 x 10(-9) M and a Bmax of 1.0 x 10(4) but did not bind to Fc gamma 2a-negative S49 variant cell line, cyc-. The flow cytometric analysis with the use of fluorescein-isothiocyanate-tagged 3A2 F(ab')2 also showed that this antibody binds to Fc gamma 2aR-positive cells, P388D1 and S49, but not to Fc gamma 2aR-negative cells, cyc-. Monomeric and heat-aggregated IgG2a (13-fold molar excess) inhibited the binding of the radioiodinated 3A2 F(ab')2 to P388D1 cells by 70 and 49%, respectively, whereas the inhibition by monomeric and heat-aggregated IgG2b was 17 and 39%, respectively; 3A2 F(ab')2 (100-fold molar excess) inhibited the binding of IgG2a and IgG2b to P388D1 cells by 90 and 24%, respectively, whereas the inhibition of binding of these IgG to S49 cells was 79 and 49%, respectively. Western blotting analysis showed that 3A2 antibody recognizes a major protein (Mr = 100,000) and a minor component (Mr = 80,000) separated by SDS-PAGE of P388D1 or S49 cell lysates under nonreducing condition, whereas under reducing condition, this antibody recognized a major protein (Mr = 50,000) and two additional minor components (Mr = 40,000 and 35,000). Fc gamma 2aR may thus exist at the cell surface as a disulfide linked dimer of a subunit of Mr of 50,000, which could be partially degraded during the isolation to smaller fragments of 40,000 and 35,000 Mr peptides which are still held together by interchain disulfide bond.(ABSTRACT TRUNCATED AT 250 WORDS)

[A case of Legionnaires' disease associated with rhabdomyolysis].

Legionnaires' disease is primarily a respiratory disorder, but recently several cases with extrapulmonary manifestations are reported. We report a case of Legionnaires' disease associated with pneumonia, diarrhea, central nerve disorders and rhabdomyolysis. The pathogenesis of rhabdomyolysis in Legionnaires' disease remains speculative. Endotoxin isolated from Legionella pneumophila may play a role in the pathogenesis of the myonecrosis. An additional factor that might contribute to rhabdomyolysis in this case is severe dehydration induced by diarrhea. Pneumonia with elevated CPK levels and myoglobinuria may suggest Legionnaires' disease.

Potter's syndrome associated with renal agenesis or dysplasia. Morphological and biochemical study of the lung.

We report on four autopsy cases of Potter's syndrome associated with characteristic Potter's face, pulmonary hypoplasia, and renal agenesis or dysplasia. There were no pathologic differences in typical cases with bilateral renal agenesis and variant cases with renal dysplasia instead of renal agenesis. All cases showed bilateral pulmonary hypoplasias and immature lung microscopically. Hyaline membrane disease was found in three cases in spite of late gestation. In one case with renal dysplasia, disaturated phosphatidylcholine, a pulmonary surfactant phospholipid, was measured and found to be decreased in comparison with that in age-matched controls. This suggests that functionally immature lung may be one feature of Potter's syndrome that is similar to hyaline membrane disease.

Analysis of translational fidelity of ribosomes with protamine messenger RNA as a template.

A novel method was developed to estimate the translational fidelity of mammalian ribosomes in vitro with protamine mRNA of rainbow trout as template. Protamines are mixtures of basic proteins consisting of only seven types of amino acids (Arg, Ile, Val, Ser, Pro, Ala, and Gly), arginine (codon, AGR and CGN) being abundant. Taking advantage of the absence of lysine (codon, AAG) in the proteins, we determined the misincorporation of this amino acid into protamines in a cell-free translation system consisting of mouse liver ribosomes, protamine mRNA, [3H]lysine, [14C]arginine, and seven unlabeled amino acids: Ile, Val, Ser, Pro, Ala, Gly, and Met. After the reaction, translation products were analyzed by either sucrose gradient centrifugation or polyacrylamide gel electrophoresis. In the former method, radioactive protamines are mostly found on monosomes, but not on polysomes, probably because of the basic nature of the proteins. The error frequency was calculated from the molar ratio of [3H]lysine to [14C]arginine incorporated into protamines with an appropriate correction. The frequency was found to be 0.0006-0.002. This method enabled us to determine the frequency of misrecognition of purine bases at the second position of arginine codons in mRNA.