Association of Lower-Extremity Muscle Performance and Physical Activity Level and Intensity in Middle-Aged and Older Adults: A Doubly Labeled Water and Accelerometer Study.

OBJECTIVES: The purpose of this study was to examine if there is a relationship between lower-extremity muscle performance (LEMP) and physical activity, especially the physical activity level (PAL) value, in community-dwelling middle-aged and older adults. DESIGN: Cross-sectional study. SETTING: Community-based. PARTICIPANTS: Participants were 54 community-dwelling and independent middle-aged and older individuals (aged 54-89 years). MEASUREMENTS: Physical activity level was calculated from the total energy expenditure of each participant obtained using the doubly labeled water method (PALDLW) and estimated basal metabolic rate. Daily step count and intensity of physical activity was monitored with a triaxial accelerometer, and LEMP was assessed using the five-repetition sit-to-stand test (STS-5) and vertical jumping (VJ). RESULTS: The results of STS-5 nearly negatively correlated with those of PALDLW when analysing the middle-aged and older man and woman, separately. VJ positively correlated with PALDLW when analysing the middle-aged and older men and woman, separately. The relationship between LEMP (e.g. STS-5 and VJ) and PAL were maintained, regardless of sex and body composition. PALDLW was significantly positively correlated with LPA, MVPA, and steps, and significantly negatively correlated with sedentary time. The relationship PALDLW and steps was described as following equation: PALDLW = 0.0000392 × steps +1.531. CONCLUSIONS: These findings suggest that PALDLW is a key contributor to increasing LEMP among middle-aged and older adults. Maintaining high PALDLW may be beneficial to independent living, and participation in recreational and social activities in middle-aged and older adults.

Interlayer structure and self-healing in suspensions of brush-stabilized nanoplatelets with smectic order.

We have investigated the rheology of an uncured epoxy fluid containing high aspect ratio (length/thickness ≈ 160) α-zirconium phosphate (ZrP) nanoplatelets with smectic order. The nanoplatelets were exfoliated into monocrystalline sheets with uniform thickness using a monoamine-terminated oligomer. The oligomers were densely grafted to the plate surfaces and behave as a molecular brush. Suspensions containing ∼ 2 vol.% ZrP and above show liquid crystalline order with scattering peaks characteristic of a smectic (layered) mesophase. At much higher loading, ∼ 4 vol.% ZrP, there is a sharp transition in visual appearance, steady shear rheology, and linear and non-linear viscoelasticity that is attributed to the reversible interdigitation of oligomer chains between closely spaced layers. The oligomers are proposed to serve as inter-lamellar bridges that store elastic stresses for intermediate rates of deformation, but are able to relax on longer time scales. Under steady shearing conditions, the smectic suspensions with "overlapped" microstructure show a discontinuous flow curve characteristic of shear banding that is attributed to the dynamic pull-out of oligomer chains from the overlap region. At high shear rates, the limiting viscosity of the concentrated suspensions is on the same order of magnitude as the unfilled suspending fluid. When the rate of deformation is reduced below a critical time scale, the original network strength, and corresponding microstructure, is recovered through a passive self-healing process. The unique combination of concentration-dependent yield stress, low post-yield viscosity, and self-healing is potentially useful for various applications in the liquid state, and desirable for scalable processing of nanocomposite materials for structural applications.

[Mitral valve replacement for cabergoline-related severe mitral regurgitation].

An 82-year-old man was referred to our hospital because of progressive heart failure. He had Parkinson's disease and had been treated with cabergoline during the preceding 4 years and 8 months. Echocardiography revealed severe mitral regurgitation through retracted mitral leaflets with incomplete coaptation. Heart failure persisted despite pharmacologic therapy, so the mitral valve was surgically replaced with a biological valve. Histologic analysis showed fibrous thickened mitral chordae with myxoid degeneration. These characteristics of the mitral valve of our patient are similar to the valvular heart disease described with the use of cabergoline. Clinicians must be care of valvular heart disease whenever they treat Parkinson's disease patients with cabergoline.

Pollen-induced airway inflammation, hyper-responsiveness and apoptosis in a murine model of allergy.

BACKGROUND: Previous studies indicate that murine models are useful tools for studying the allergic diseases, including certain aspects of bronchial asthma such as cellular tissue inflammation and pulmonary function. OBJECTIVE: To develop an experimental model of allergic lung inflammation based on a relevant human allergen, olive pollen, and to establish the immunological, cellular and functional airway features of the allergic response in this model. METHODS: Induction of systemic allergic response was achieved by the subcutaneous administration of Olea europaea extract in BALB/c mice. Olea-specific Igs (IgG1, IgG2a and IgE) and cytokines from splenocyte cultures IL-4, IL-5 IL-10, IL-13 and IFN-gamma were measured. Allergic airway response was generated by transnasal instillation of the allergens. Airway responsiveness was monitored by non-invasive methacholine inhalation challenge. Lungs were paraffin embedded and histologically analysed. Apoptosis was studied by the TUNEL technique in the lung tissue and through cell cycle analysis by flow cytometry in splenocytes. RESULTS: Our results demonstrate that Olea-sensitized mice develop a specific allergic antibody (IgG1 and IgE) and cytokine (IL-4, IL-5, IL-10 and IL-13) response. After transnasal Olea instillation, they show inflammatory infiltration of lung tissue, mucus secretion and non-specific hyper-responsiveness in the airway. Concomitantly, differences in the rate of apoptosis are observed in the lung cells as well as a significant reduction of spontaneous apoptosis in the splenocytes of allergic mice. CONCLUSION: We present a novel animal model of olive pollen-allergic disease. This model presents traits associated with human allergic asthma and could be an interesting tool in the study of underlying molecular mechanisms and in exploring the therapeutic approaches to this disease.

Anisakis simplex allergy: a murine model of anaphylaxis induced by parasitic proteins displays a mixed Th1/Th2 pattern.

The study of the singular hypersensitivity reactions to Anisakis simplex (A.s) proteins, may help us to undestand many of the unknown immune interactions between helmiths infections and allergy. We have developed a murine model of allergy to A. simplex, that mimics human A. simplex allergy to study the specific aspects of anaphylaxis induced by parasites. Male C3H/HeJ mice were intraperitoneally sensitized to A. simplex. Mice were then intravenous or orally challenged with A. simplex. Antigen-specific immunoglobulins, polyclonal IgE, anaphylactic symptoms, plasma histamine levels and cytokine profiles were determined. Comparative IgE immunoblot analyses were also performed. Specific IgE, IgG(1) and IgG(2a) were detected in sensitized mice since week 3. Polyclonal IgE raised and peaked with different kinetics. Intravenous A. simplex challenge produced anaphylaxis in mice, accompanied by plasma histamine release. Oral A. simplex challenge in similarly sensitized mice did not caused symptoms nor histamine release. Numerous A. simplex allergens were recognized by sensitized mouse sera, some of them similar to human serum. The A. simplex stimulated splenocytes released IL-10, IFN-gamma, IL-4, IL-13 and IL-5. We describe a new animal model of anaphylaxis. It exhibits characteristics of type I hypersensitivity reactions to Anisakis simplex similar to those observed in allergic humans. Different responses to i.v. or oral A. simplex challenges emerged, which did not reflect a window tolerization period. The cytokine profile developed (mixed Th(1)/Th(2) pattern) differed from the observed in classical models of anaphylaxis or allergy to food antigens. This model may permit to investigate the peculiar allergic reactions to parasitic proteins.

Long-period accelerometer monitoring shows the role of physical activity in overweight and obesity.

CONTEXT: Physical activity (PA) plays an important role in obesity. A new accelerometer has been developed to assess total energy expenditure as well as PA. OBJECTIVE: To investigate the association of PA with overweight and obesity in Japanese men and women, a large cross-sectional study was performed using a single-axis accelerometer. DESIGN, SETTING AND PARTICIPANTS: Population-based cross-sectional study of Japanese 18-84 y of age. Height, body weight and PA were measured in 400 male and 388 female Japanese volunteers from 1999 to 2000. The outcome measurements were overweight and obesity, which are defined as a body mass index >/=25 kg/m(2). PA was measured for 1 to 4 weeks and was then categorized into three activity levels, which were defined as light, moderate and vigorous PA. RESULTS: Prevalence of overweight and obesity was 22.3%. Number of steps and time spent in moderate and vigorous PA per day were lower in overweight and obese individuals. No difference was found in time spent in light PA. Individuals who are in the 4th and 5th quintile of moderate and vigorous PA showed a significantly lower body mass index. When odd ratios (ORs) of overweight and obesity estimated by logistic regression were used as effect measures, overweight and obesity were negatively associated with vigorous PA (ORs=0.91). CONCLUSION: These results indicate that overweight and obese individuals have a lower step rate and are spending less time for moderate to vigorous PA. Participation in vigorous PA is an important predictor of overweight and obesity.

Overexpression of lipoprotein lipase improves insulin resistance induced by a high-fat diet in transgenic rabbits.

AIMS/HYPOTHESIS: Dysfunctions of lipoprotein lipase (LPL) have been found to be associated with dyslipidaemias, atherosclerosis, obesity and insulin resistance. There are two conflicting hypotheses regarding the roles of LPL in glucose metabolism and insulin resistance. Whether systemically increased LPL activity would be beneficial or detrimental to insulin sensitivity is yet to be resolved. To address this issue, we studied transgenic rabbits overexpressing human LPL transgene. METHODS: LPL transgenic and control rabbits were fed a 10% high-fat diet (HFD) for 16 weeks. To evaluate glucose metabolism, we compared plasma levels of glucose and insulin in transgenic rabbits with control rabbits and performed an intravenous glucose tolerance test. In addition, we measured adipose tissue accumulation in HFD-fed rabbits. RESULTS: Increased LPL activity in transgenic rabbits resulted in a significant reduction of plasma triglycerides and non-esterified fatty acids, but not in basal levels of glucose and insulin. HFD feeding induced an elevation of plasma glucose levels accompanied by hyperinsulinaemia in control rabbits, but was significantly inhibited in transgenic rabbits. The intravenous glucose tolerance test showed that transgenic rabbits had faster glucose clearance associated with lower levels of insulin secretion than control rabbits. In addition, there was a significant reduction of body adipose tissue in transgenic rabbits compared with in control rabbits fed an HFD. Scanning electron microscopic examination revealed that adipocytes in transgenic rabbits were predominately small cells. CONCLUSIONS/INTERPRETATION: Our results showed that systemically increased LPL activity improves insulin resistance and reduces adipose accumulation in transgenic rabbits, indicating that systemic elevation of LPL may have potential benefits for the treatment of insulin resistance and obesity.

Randomized trial with itraconazole, ketoconazole and sulfadiazine in paracoccidioidomycosis.

Forty-two patients with active paracoccidioidomycosis were randomized to receive itraconazole (50-100 mg d(-1)), ketoconazole (200-400 mg d(-1)) or sulfadiazine (100-150 mg kg d(-1) up to 6 g d(-1)) for 4-6 months, followed by slow release sulfa until negativity of serological tests. All 14 patients in itraconazole and sulfadiazine groups and 13 in the ketoconazole group showed an adequate clinical response to the chemotherapy. One patient in the latter group showed treatment failure according to clinical and mycological criteria. The test of the hypothesis that the drugs reduced antibody levels up to ten months of treatment showed a p value equal to 0.0001 for itraconazole, 0.017 for ketoconazole and 0.0012 for sulfadiazine; this reduction was similar for the three groups. In this first randomized study for the treatment of paracoccidioidomycosis we could not show superiority of any one regimen over the others in the clinical and serological responses of patients with the moderately severe form of the disease.

Dietary obesity-resistance and muscle oxidative enzyme activities of the fast-twitch fibre dominant rat.

OBJECTIVES: To clarify whether the muscle fibre composition and/or muscle oxidative enzyme activity are related to dietary body weight gain and abdominal fat accumulation. METHODS: Genetically fast-twitch fibre dominant rats (FFDR) and control rats (CR) were divided into low-fat (20% of energy from fat) or high-fat (60% of energy from fat) diet groups: CR with a low-fat diet (CL); CR with a high-fat diet (CH); FFDR with a low-fat diet (FL); and FFDR with a high-fat diet (FH). After 6 weeks of following such diets, the body weight gain, abdominal fat content, food intake, muscle fibre composition and oxidative enzyme activities were estimated. RESULTS: The total body weight gain in CH was from 18 to 62% higher than in the other groups (P<0.05) and percentage abdominal fat in CH was also from 26 to 61% higher than in the other groups (P<0.05), while the energy intake did not differ among the groups. The percentage of type IIX fibres of M. gastrocnemius in FL (33.4%) and FH (36.3%) were higher than in CL (16.8%) and CH (19.8%; P<0.05), and the type IIA fibres of M. soleus in FL (14.1%) and FH (11.8%) were higher than in CL (2.0%) and CH (3.5%; P<0.05). The citrate synthase (CS) activity of of M. plantaris in FL and FH were higher than CL (46 and 54%, respectively, P<0.05). beta-Hydroxyacyl CoA dehydrogenase (HAD) activity in FL and FH were higher than in CL (21 and 31%, respectively, P<0.05) and that in FH was higher than CH (23%, P<0.05). On the other hand, the enzyme activities of M. gastrocnemius and soleus were identical among the groups. CONCLUSION: The FFDR was more obesity-resistant than the CR after a high-fat diet. These results suggest that the muscle oxidative capacity rather than muscle fibre composition is a possible determinant of obesity.

[Clinical analysis of 16 cases of malignant head and neck melanoma].

Subjects were 16 patients--5 men and 11 women aged 46-82 years (mean: 61 years)--with malignant melanoma of the head and neck treated at our clinic from 1972 to 1988. Histologically, 1 subjects was amelanotic and 15 melanotic type. Primary lesions were 10 involving the nasal cavity, 2 the paranasal sinus, 2 the gingiva, 1 the lip, and 1 primary unknown. They were treated with or without multimodal surgery, radiation, chemotherapy, and immunotherapy. Of 12 treated using local surgery, local recurrence was seen in 6 in 7 areas. Two-year survival was 44% and 5-year survival 22%. The prognosis of malignant head and neck melanoma is poor but has gradually improved due to preoperative decisions on disease spread and the introduction of multimodal therapy.

Insulin alters heterogeneous nuclear ribonucleoprotein K protein binding to DNA and RNA.

The interaction of the multimodular heterogeneous nuclear ribonucleoprotein (hnRNP) K protein with many of its protein and nucleic acid partners is regulated by extracellular signals. Acting as a docking platform, K protein could link signal-transduction pathways to DNA- and RNA-directed processes such as transcription, mRNA processing, transport, and translation. Treatment of hepatocyte culture with insulin increased K protein tyrosine phosphorylation. Insulin altered K protein interaction with RNA and DNA in vitro. Administration of insulin into mice had similar effects on K protein in liver. Coimmunoprecipitations of RNA with K protein revealed preferential in vivo K protein binding of a subset of transcripts, including the insulin-inducible c-fos mRNA. These results suggest a class of insulin pathways that signal nucleic acid-directed processes that involve K protein.

Effect of mild exercise training on glucose effectiveness in healthy men.

OBJECTIVE: To detect whether mild exercise training improves glucose effectiveness (S(G)), which is the ability of hyperglycemia to promote glucose disposal at basal insulin, in healthy men. RESEARCH DESIGN AND METHODS: Eight healthy men (18-25 years of age) underwent ergometer training at lactate threshold (LT) intensity for 60 min/day for 5 days/week for 6 weeks. An insulin-modified intravenous glucose tolerance test was performed before as well as at 16 h and 1 week after the last training session. S(G) and insulin sensitivity (S(I)) were estimated using a minimal-model approach. RESULTS: After the exercise training, VO(2max) and VO(2) at LT increased by 5 and 34%, respectively (P < 0.05). The mild exercise training improves S(G) measured 16 h after the last training session, from 0.018 +/- 0.002 to 0.024 +/- 0.001 min(-1) (P < 0.05). The elevated S(G) after exercise training tends to be maintained regardless of detraining for 1 week (0.023 +/- 0.002 min(-1), P = 0.09). S(I) measured at 16 h after the last training session significantly increased (pre-exercise training, 13.9 +/- 2.2; 16 h, 18.3 +/- 2.4, x10(-5). min(-1). pmol/l(-1), P < 0.05) and still remained elevated 1 week after stopping the training regimen (18.6 +/- 2.2, x10(-5). min(-1). pmol/l(-1), P < 0.05). CONCLUSIONS: Mild exercise training at LT improves S(G) in healthy men with no change in the body composition. Improving not only S(I) but also S(G) through mild exercise training is thus considered to be an effective method for preventing glucose intolerance.

Granzyme-B-containing lymphocyte involvement in epidermal injury in graft-versus-host disease.

BACKGROUND: Skin lesions from graft-versus-host disease (GVHD) show histological features of epidermal cell death with lymphocyte infiltration. Perforin and granzyme B are involved in the process of apoptosis induced by cytotoxic T lymphocytes (CTL). OBJECTIVE: To elucidate the role of CTL in the mechanism of epidermal injury in GVHD. METHODS: We studied immunohistochemical staining for granzyme B and perforin in the skin lesions of 8 patients who developed GVHD after bone marrow transplantation. RESULTS: Granzyme-B-positive lymphocytes were CD8 positive and were observed in the epidermis of 3 out of 6 specimens in acute GVHD, and of 5 specimens of chronic GVHD except for 1 sclerotic type in which it was negative. Perforin-positive lymphocytes were observed in the epidermis of the specimens from 1 acute and 1 chronic GVHD. CONCLUSIONS: Granzyme B derived from CTL may be involved in the mechanisms of epidermal injury in GVHD.

Nitric oxide increases glucose uptake through a mechanism that is distinct from the insulin and contraction pathways in rat skeletal muscle.

Insulin, contraction, and the nitric oxide (NO) donor, sodium nitroprusside (SNP), all increase glucose transport in skeletal muscle. Some reports suggest that NO is a critical mediator of insulin- and/or contraction-stimulated transport. To determine if the mechanism leading to NO-stimulated glucose uptake is similar to the insulin- or contraction-dependent signaling pathways, isolated soleus and extensor digitorum longus (EDL) muscles from rats were treated with various combinations of SNP (maximum 10 mmol/l), insulin (maximum 50 mU/ml), electrical stimulation to produce contractions (maximum 10 min), wortmannin (100 nmol/l), and/or the NO synthase (NOS) inhibitor NG-monomethyl-L-arginine (L-NMMA) (0.1 mmol/l). The combinations of SNP plus insulin and SNP plus contraction both had fully additive effects on 2-deoxyglucose uptake. Wortmannin completely inhibited insulin-stimulated glucose transport and only slightly inhibited SNP-stimulated 2-deoxyglucose uptake, whereas L-NMMA did not inhibit contraction-stimulated 2-deoxyglucose uptake. SNP significantly increased the activity of the alpha1 catalytic subunit of 5'AMP-activated protein kinase (AMPK), a signaling molecule that has been implicated in mediating glucose transport in fuel-depleted cells. Addition of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) (1 mg/ml) to the drinking water of rats for 2 days failed to affect the increase in muscle 2-deoxyglucose uptake in response to treadmill exercise. These data suggest that NO stimulates glucose uptake through a mechanism that is distinct from both the insulin and contraction signaling pathways.

[Bone mineral density of the calcaneus and related factors in men].

In this cross-sectional study, the bone mineral density of the calcaneus was investigated in healthy young (n = 35, 22-33 years) and middle-aged (n = 49, 45-59 years) men. The relationships among the bone mineral density, body fatness, physical fitness, physical activity in recent and past days, smoking, alcohol, and sex hormones (free testosterone, estradiol, and dehydroepiandrosterone-sulfate; DHEA-S) and sex hormone binding globulin were evaluated. The speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured by ultrasonic measurement. There was no association between age and bone density in each group. In the young group, there was a positive correlation between the body mass index (BMI) and BUA and between the training time during junior high school and BUA, and an inverse correlation between alcohol consumption and SOS after adjustment for the confounding factors using partial correlation analysis. The level of DHEA-S was weakly but not significantly associated with BUA. In the middle-aged group, there was an inverse correlation between the waist to hip ratio and SOS, and between the height of jump and SOS after adjustment for the confounding factors using partial correlation analysis. These results suggest that different factors may affect bone density in the young and middle-aged men. In young men, the higher BMI and the longer training time during boyhood may have a positive effect, and heavy alcohol consumption may have a negative effect on bone density. In middle-aged men, abdominal fat accumulation has a negative effect and leg muscle power has a positive effect on bone density.

Interaction of two multifunctional proteins. Heterogeneous nuclear ribonucleoprotein K and Y-box-binding protein.

The heterogeneous nuclear ribonucleoprotein (hnRNP) K, a component of the hnRNP particles, appears to be involved in several steps of regulation of gene expression. To gain insight into mechanisms of K protein action, we performed two-hybrid screens using full-length hnRNP K as a bait. Several novel protein partners were identified, including Y-box-binding protein (YB-1), splicing factors 9G8 and SRp20, DNA-methyltransferase, hnRNP L, and hnRNP U. In vitro binding studies and co-immunoprecipitation from cellular extracts provided evidence for direct interaction between hnRNP K and YB-1. Two distinct domains in YB-1 were responsible for binding to K protein. Each protein was able to transactivate transcription from a polypyrimidine-rich promoter; however, this effect was reduced when K and YB-1 proteins were coexpressed suggesting a functional interaction between these two proteins.

Tumoral calcinosis: a case report with an electron microscopic study.

A 68-year-old woman developed large subcutaneous masses on her abdomen and thighs after a bruise sustained in a traffic accident. She had severe pain when sitting up straight. Histological examination revealed calcified tissues in the entire dermis of the injured areas. On electron microscopy, crystalline materials were observed in the dermis, which seemed to be formed by the deposition of hydroxyapatite on unusual proteoglycan. In a vessel wall, a thick, layered basement membrane was observed. This suggests that vascular injury and subsequent hypoxia play a role in the process of calcinosis. We performed a partial resection with good results in alleviating the patient's pain.

Role of tyrosine phosphorylation in the regulation of the interaction of heterogenous nuclear ribonucleoprotein K protein with its protein and RNA partners.

The heterogeneous nuclear ribonucleoprotein K protein recruits a diversity of molecular partners and may act as a docking platform involved in such processes as transcription, RNA processing, and translation. We show that K protein is tyrosine-phosphorylated in vitro by Src and Lck. Treatment with H(2)O(2)/Na(3)VO(4), which induces oxidative stress, stimulated tyrosine phosphorylation of K protein in cultured cells and in intact livers. Tyrosine phosphorylation increased binding of Lck and the proto-oncoprotein Vav to K protein in vitro. Oxidative stress increased the association of K protein with Lck and Vav, suggesting that tyrosine phosphorylation regulates the ability of K protein to recruit these effectors in vivo. Translation-based assay showed that K protein is constitutively bound to many mRNAs in vivo. Native immunoprecipitated K protein-mRNA complexes were disrupted by tyrosine phosphorylation, suggesting that the in vivo binding of K protein to mRNA may be responsive to the extracellular signals that activate tyrosine kinases. This study shows that tyrosine phosphorylation of K protein regulates K protein-protein and K protein-RNA interactions. These data are consistent with a model in which functional interaction of K protein is responsive to changes in the extracellular environment. Acting as a docking platform, K protein may bridge signal transduction pathways to sites of nucleic acid-dependent process such as transcription, RNA processing, and translation.