Longitudinal study of factors affecting taste sense decline in old-old individuals.

The sense of taste plays a pivotal role for personal assessment of the nutritional value, safety and quality of foods. Although it is commonly recognised that taste sensitivity decreases with age, alterations in that sensitivity over time in an old-old population have not been previously reported. Furthermore, no known studies utilised comprehensive variables regarding taste changes and related factors for assessments. Here, we report novel findings from a 3-year longitudinal study model aimed to elucidate taste sensitivity decline and its related factors in old-old individuals. We utilised 621 subjects aged 79-81 years who participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians Study for baseline assessments performed in 2011 and 2012, and then conducted follow-up assessments 3 years later in 328 of those. Assessment of general health, an oral examination and determination of taste sensitivity were performed for each. We also evaluated cognitive function using Montreal Cognitive Assessment findings, then excluded from analysis those with a score lower than 20 in order to secure the validity and reliability of the subjects' answers. Contributing variables were selected using univariate analysis, then analysed with multivariate logistic regression analysis. We found that males showed significantly greater declines in taste sensitivity for sweet and sour tastes than females. Additionally, subjects with lower cognitive scores showed a significantly greater taste decrease for salty in multivariate analysis. In conclusion, our longitudinal study revealed that gender and cognitive status are major factors affecting taste sensitivity in geriatric individuals.

Dietary Intake Is Associated with Occlusal Force Rather Than Number of Teeth in 80-y-Old Japanese.

There has been a growing interest in the association between the number of teeth and dietary intake in older populations. However, people around the age of 80 y have frequently lost most of their teeth, and dental prostheses replacing the missing teeth play an important role in masticatory function. Therefore, masticatory function cannot be evaluated by the number of teeth alone. The occlusal force of the complete dental arches is an index of masticatory function, reflecting not only the number of teeth, but the effect of removable dentures. The purpose of this cross-sectional study was to determine the relative importance of the number of teeth and occlusal force in association with dietary intake in 80-y-old Japanese people. This study included 760 community-dwelling Japanese people aged 79 y to 81 y. The authors measured bilateral maximal occlusal force in the intercuspal position using pressure-sensitive sheets. Removable denture wearers kept their dentures in place during the measurements. Energy-adjusted food groups and nutrient intake during the preceding month were assessed by a brief self-administered diet history questionnaire. The authors assessed linear trends in food and nutrient intake in relation to the number of teeth and occlusal force after adjusting for gender and socioeconomic status (education level, financial status, family structure, resident area and BMI). P values of < 0.05 were considered to be statistically significant. The authors found that the number of teeth was not associated with the energy-adjusted intake of any food group examined. In contrast, a decline in occlusal force was significantly associated with a lower intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most vitamins and minerals ( P for trend < 0.05). We conclude that food and nutrient intake was more closely associated with occlusal force than the number of teeth in community-dwelling Japanese people aged 79 y to 81 y. Knowledge Transfer Statement: This cross-sectional study of older Japanese people showed that, after controlling for considerable covariates, occlusal force rather than the number of teeth is positively associated with energy-adjusted intake of vegetables, fish and shellfish, protein, polyunsaturated fatty acids, dietary fiber and most of vitamins and minerals. This means that reduced occlusal force may unconsciously lead older people toward a habitual unhealthy dietary intake. Older people have frequently lost most of their teeth and require prosthetics to restore masticatory function. Bilateral occlusal force is therefore a better measure of masticatory function than the number of remaining teeth. Our findings suggest that prosthetic rehabilitation is a significant factor in the prevention and management of chronic diseases and frailty through better dietary intake in older populations.

Factors related to taste sensitivity in elderly: cross-sectional findings from SONIC study.

The sense of taste is important, as it allows for assessment of nutritional value, as well as safety and quality of foods, with several factors suggested to be associated with taste sensitivity. However, comprehensive variables regarding taste and related factors have not been utilised in previous studies for assessments of sensitivity. In the present study, we performed cross-sectional analyses of taste sensitivity and related factors in geriatric individuals who participated in the SONIC Study. We analysed 2 groups divided by age, 69-71 years (young-old, n = 687) and 79-81 years (old-old, n = 621), and performed a general health assessment, an oral examination and determination of taste sensitivity. Contributing variables were selected by univariate analysis and then subjected to multivariate logistic regression analysis. In both groups, females showed significantly better sensitivity for bitter and sour tastes. Additionally, higher cognitive scores for subjects with a fine taste for salty were commonly seen in both groups, while smoking, drinking, hypertension, number of teeth, stimulated salivary flow salt intake and years of education were also shown to be associated with taste sensitivity. We found gender and cognitive status to be major factors affecting taste sensitivity in geriatric individuals.

Association of Occlusal Force with Cognition in Independent Older Japanese People.

Recent longitudinal studies have shown the influence of multiple tooth loss on cognitive impairment, and earlier studies suggested that periodontal disease was related to cognitive decline. Tooth loss is associated with reduced masticatory function, which may affect stimulation of the central nervous system and dietary intake. Although some studies have reported a relationship between chewing ability and cognitive function, no studies have examined this area in terms of objective oral function. The aim of this study was to examine the association of occlusal force with cognitive decline in the preclinical stage among older people with higher-level functional capacity. This cross-sectional study for community-dwelling older people living in urban and rural areas in Japan examined 994 persons in the 70-y group (age range, 69-71 y) and 968 persons in the 80-y group (age range, 79-81 y). Retention of higher-level competence was defined according to the Tokyo Metropolitan Institute of Gerontology Index of Competence. Cognitive function was measured with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Oral status and function were assessed by the number of remaining teeth, periodontal pocket depth, and maximal occlusal force. Associations between the MoCA-J score and occlusal force were examined by bivariate and multivariate analysis. Approximately one-half of the participants retained higher-level functional capacity and were included in the analysis. Multiple regression analysis showed that occlusal force was significantly related to cognitive function after controlling for possible predictors including age, sex, socioeconomic status, medical condition, and handgrip strength. The number of remaining teeth and periodontal pocket depth were not significantly associated with cognitive function. Among community-dwelling older people with retained competence, maximal occlusal force was positively associated with their cognitive function. These results suggest that oral function might be a predictor for preclinical cognitive decline. Knowledge Transfer Statement: Multiple regression analysis showed that occlusal force was significantly related to cognition after controlling for possible predictors including handgrip strength as an indicator of general muscle strength, suggesting the independence of oral function. The number of remaining teeth did not have this association. The majority of older people have lost teeth and have received prosthodontic treatment, and their occlusal force is determined not only by the number of remaining teeth but also by prosthetic rehabilitation. These results can be used by clinicians focusing on prevention of tooth loss among the entire population, as well as to encourage partially edentulous and fully edentulous patients to restore their oral function with prostheses in order to eliminate a possible risk factor for cognitive impairment.

Association of periodontal status with occlusal force and food acceptability in 70-year-old adults: from SONIC Study.

This cross-sectional study aimed to investigate the association of periodontal status with occlusal force and food acceptability. We hypothesised that mastication deteriorated with reduced periodontal support, even when posterior occlusal contacts with natural teeth were maintained and the patients remained clinically asymptomatic. Participants were 482 independently living 69-71-year-olds, classified as Eichner's group A, having no mobile teeth and no periodontal symptoms. The periodontal probing depth (PPD) and restoration status of each tooth were examined. Occlusal force in the intercuspal position was measured with pressure-sensitive films. Food acceptability was evaluated from the difficulty experienced in chewing apples, grilled beef, and hard rice crackers. Multivariate regression analysis was performed to investigate the association of periodontal status with occlusal force and food acceptability. A P-value of <0.05 was considered statistically significant. Multiple linear regression analysis showed that occlusal force had significant negative associations with maximal PPD (standardised partial regression coefficient (ß) = -0.121) after controlling for gender, handgrip strength, number of teeth, and percentage of restored teeth. Approximately 15% of participants were included in the compromised food acceptability group. Logistic regression analyses showed that compromised food acceptability was significantly associated with PPD, after controlling for gender, number of teeth, and percentage of restored teeth. Periodontal probing depth (PPD) was significantly correlated with occlusal force and self-rated food acceptability after controlling for the possible confounding factors in septuagenarians, even those with complete posterior occlusal contacts and no tooth mobility.

Clinical significance of serum retinol binding protein-4 levels in patients with systemic sclerosis.

BACKGROUND: Retinol binding protein-4 (RBP-4) is a member of adipocytokines, which is potentially associated with fibrosis, vasodilation, and angiogenesis in addition to insulin resistance. OBJECTIVE: To investigate the clinical significance of serum RBP4 levels in patients with systemic sclerosis (SSc), which is a systemic autoimmune disease characterized by fibrosis and vasculopathy. METHODS: Serum RBP4 levels were determined by enzyme-linked immunosorbent assay in 62 SSc patients and 19 healthy controls. RESULTS: Similar to patients with chronic kidney disease, serum RBP4 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction. Therefore, analyses were carried out by excluding SSc patients with estimated glomerular filtration rate <60 mL/min/1.73 m(2) . Serum RBP4 levels were significantly lower in diffuse cutaneous SSc (dcSSc) than in control subjects [median (25-75 percentile); 25.8 µg/mL (19.6-47.0) vs. 43.1 µg/mL (31.7-53.4), P < 0.05], while there was no significant difference between limited cutaneous SSc (lcSSc) [28.0 µg/mL (25.4-43.3)] and control subjects. In both of dcSSc and lcSSc, patients with Raynaud's phenomenon had RBP4 levels significantly lower than those without. Furthermore, serum RBP4 levels inversely correlated with pulmonary function test results in dcSSc and with right ventricular systolic pressure in lcSSc. CONCLUSION Decreased RBP4 levels are associated with the prevalence of Raynaud's phenomenon in dcSSc and lcSSc, with the severity of interstitial lung disease in dcSSc, and with the degree of pulmonary vascular involvement in lcSSc, suggesting the possible contribution of RBP4 to the pathological events in this disorder.

Serum apelin levels: clinical association with vascular involvements in patients with systemic sclerosis.

BACKGROUND: Apelin is a bioactive peptide exerting its pro-angiogenic and pro-fibrotic effects in a context-dependent manner through the activation of its receptor APJ, which is ubiquitously expressed on the surface of various cell types. The activation of apelin/APJ signalling appears to be involved in the pathological process of fibrotic disorders, including liver cirrhosis. OBJECTIVE: As an initial step to clarify the role of apelin/APJ signalling in the pathogenesis of systemic sclerosis (SSc), we investigated serum apelin levels and their clinical association in patients with SSc. METHODS: Serum apelin levels were determined by a specific enzyme-linked immunosorbent assay in 56 SSc patients and 18 healthy controls. RESULTS: Serum apelin levels were comparable among three groups, including diffuse cutaneous SSc, limited cutaneous SSc and control subjects (1.77 ± 1.48, 1.63 ± 1.51 and 1.61 ± 0.44 ng/mL, respectively). When we classified SSc patients into three groups according to disease duration, serum apelin levels were elevated in early SSc (<3 years) compared with mid-stage SSc (3-10 years) (1.74 ± 1.26 vs. 1.02 ± 0.52 ng/mL, P < 0.05). Importantly, in late stage SSc (>10 years), the prevalence of severe vascular involvements, including intractable skin ulcers, scleroderma renal crisis and pulmonary arterial hypertension, was significantly higher in patients with elevated serum apelin levels than in those without (100% vs. 20%, P < 0.05). CONCLUSION: Apelin may be associated with altered and activated angiogenesis prior to fibrotic responses in early SSc and with the development of proliferative vasculopathy in late stage SSc.

Serum adiponectin levels inversely correlate with the activity of progressive skin sclerosis in patients with diffuse cutaneous systemic sclerosis.

BACKGROUNDS: Adiponectin has been demonstrated to be one of anti-inflammatory and anti-fibrotic factors, suggesting the potential of this cytokine to be involved in the developmental process of systemic sclerosis (SSc). OBJECTIVE: The aim of this study was to investigate the clinical significance of serum adiponectin levels in patients with SSc. Methods Serum adiponectin levels were determined using enzyme-linked immunosorbent assay (ELISA) in 32 patients with diffuse cutaneous SSc (dcSSc), 28 with limited cutaneous SSc (lcSSc) and 27 healthy controls. No significant difference between these groups existed in terms of gender, age and body mass index. RESULTS: Serum adiponectin levels in dcSSc patients (4.93 ± 6.48 µg/mL) were significantly lower than those in lcSSc patients (9.69 ± 7.61 µg/mL, P < 0.01) and healthy controls (9.36 ± 5.57 µg/mL, P < 0.01). dcSSc patients with disease duration of ≤5 years had significantly decreased serum adiponectin levels (2.15 ± 1.69 µg/mL) than those with disease duration of >5 years (13.29 ± 8.36 µg/mL, P < 0.01), lcSSc patients with disease duration of ≤5 years (8.07 ± 7.98 µg/mL, P < 0.05), lcSSc patients with disease duration of >5 years (10.9 ± 7.34 µg/mL, P < 0.01) and healthy controls (9.36 ± 5.57 µg/mL, P < 0.01). Longitudinal studies in five patients with early dcSSc treated with oral prednisone demonstrated that serum adiponectin levels inversely correlate with the activity of progressive skin sclerosis in dcSSc patients. CONCLUSION: Serum levels of adiponectin may serve as a useful marker to evaluate the activity of progressive skin sclerosis in dcSSc.

Serum Tie2 levels: clinical association with microangiopathies in patients with systemic sclerosis.

BACKGROUND: Tie2 and its ligand, angiopoietins (Ang), regulate the transition between vascular quiescence and angiogenesis. Although defective angiogenesis is one of the major causes of microangiopathies in systemic sclerosis (SSc), the role of Ang/Tie2 signalling in the development of SSc has never been examined. OBJECTIVE: To investigate the clinical significance of the soluble Tie2 domain (sTie2) in serum samples from SSc patients. METHODS: Serum sTie2 levels were determined by a specific enzyme-linked immunosorbent assay in 48 SSc patients and nine normal controls. RESULTS: There was no significant difference in serum sTie2 levels between SSc patients and healthy controls (14.8 ± 3.4 vs. 14.7 ± 1.1 ng/mL). When we set the cut-off value at 16.97 ng/mL (mean + 2SD) based on the data of normal controls, 27% of SSc patients showed elevated serum sTie2 levels. The frequencies of nailfold bleeding and pulmonary arterial hypertension (PAH) were significantly higher in patients with increased serum sTie2 levels than in those with sTie2 levels not elevated (70% vs. 47% and 60% vs. 21%, respectively, P < 0.05). There was also a trend towards the elevation of serum sTie2 levels in SSc patients with PAH compared to those without; however, it did not reach statistical significance (16.7 ± 3.6 vs. 14.2 ± 3.4 ng/mL, P = 0.059). CONCLUSION: Soluble Tie2 domain (sTie2) may be related to the development of vascular abnormalities in SSc, possibly by modulating the Ang/Tie2-mediated angiogenic process. Furthermore, the serum sTie2 levels may serve as a useful marker for SSc-related PAH, contributing to early diagnosis and therapeutic intervention.

Chronic administration of DSP-7238, a novel, potent, specific and substrate-selective DPP IV inhibitor, improves glycaemic control and beta-cell damage in diabetic mice.

AIMS: The purpose of this study is to assess the in vitro enzyme inhibition profile of DSP-7238, a novel non-cyanopyrrolidine dipeptidyl peptidase (DPP) IV inhibitor and to evaluate the acute and chronic effects of this compound on glucose metabolism in two different mouse models of type 2 diabetes. METHODS: The in vitro enzyme inhibition profile of DSP-7238 was assessed using plasma and recombinant enzymes including DPP IV, DPP II, DPP8, DPP9 and fibroblast activation protein alpha (FAPalpha) with fluorogenic substrates. The inhibition type was evaluated based on the Lineweaver-Burk plot. Substrate selectivity of DSP-7238 and comparator DPP IV inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin) was evaluated by mass spectrometry based on the changes in molecular weight of peptide substrates caused by release of N-terminal dipeptides. In the in vivo experiments, high-fat diet-induced obese (DIO) mice were subjected to oral glucose tolerance test (OGTT) following a single oral administration of DSP-7238. To assess the chronic effects of DSP-7238 on glycaemic control and pancreatic beta-cell damage, DSP-7238 was administered for 11 weeks to mice made diabetic by a combination of high-fat diet (HFD) and a low-dose of streptozotocin (STZ). After the dosing period, HbA1c was measured and pancreatic damage was evaluated by biological and histological analyses. RESULTS: DSP-7238 and sitagliptin both competitively inhibited recombinant human DPP IV (rhDPP IV) with K(i) values of 0.60 and 2.1 nM respectively. Neither vildagliptin nor saxagliptin exhibited competitive inhibition of rhDPP IV. DSP-7238 did not inhibit DPP IV-related enzymes including DPP8, DPP9, DPP II and FAPalpha, whereas vildagliptin and saxagliptin showed inhibition of DPP8 and DPP9. Inhibition of glucagon-like peptide-1 (GLP-1) degradation by DSP-7238 was apparently more potent than its inhibition of chemokine (C-X-C motif) ligand 10 (IP-10) or chemokine (C-X-C motif) ligand 12 (SDF-1alpha) degradation. In contrast, vildagliptin and saxagliptin showed similar degree of inhibition of degradation for all the substrates tested. Compared to treatment with the vehicle, single oral administration of DSP-7238 dose-dependently decreased plasma DPP IV activity and improved glucose tolerance in DIO mice. In addition, DSP-7238 significantly decreased HbA1c and ameliorated pancreatic damage following 11 weeks of chronic treatment in HFD/STZ mice. CONCLUSIONS: We have shown in this study that DSP-7238 is a potent DPP IV inhibitor that has high specificity for DPP IV and substrate selectivity against GLP-1. We have also found that chronic treatment with DSP-7238 improves glycaemic control and ameliorates beta-cell damage in a mouse model with impaired insulin sensitivity and secretion. These findings indicate that DSP-7238 may be a new therapeutic agent for the treatment of type 2 diabetes.

Sézary syndrome treated with narrowband ultraviolet B: time-course measurement of serum levels of CCL17/CCL27.

We describe a patient with Sézary syndrome (SS) who was successfully treated with topical steroid and narrowband UVB. Sézary cells in peripheral blood correlated with severity of skin lesions. In addition, serum levels of CCL17 and CCL27 decreased as disease activity improved. These chemokines may be important for the pathogenesis of SS.

Activation of c-Jun NH2-terminal kinase (JNK) pathway during islet transplantation and prevention of islet graft loss by intraportal injection of JNK inhibitor.

AIMS/HYPOTHESIS: Although application of the Edmonton protocol has markedly improved the outcome for pancreatic islet transplantation, the insulin independence rate after islet transplantation from one donor pancreas has remained low. During the isolation process and subsequent clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. The aim of this study was to map the c-Jun NH2-terminal kinase (JNK) pathway that mediates islet loss during islet transplantation and to clarify whether intraportal injection with JNK inhibitor during islet transplantation can prevent islet graft loss. METHODS: We measured JNK activity in the liver, fat and muscle of diabetic mice and in the liver immediately after islet transplantation. We examined the effect of intraportal injection of JNK inhibitory peptide at islet transplantation. RESULTS: JNK activity became progressively higher at least until 24 h after transplantation. The cell-permeable peptide of JNK inhibitor was delivered not only in the liver but also in other insulin target organs, preventing JNK activation in the liver at least until 24 h after transplantation and reducing JNK activity in these insulin target organs. Moreover, the peptide inhibitor prevented islet graft loss immediately after transplantation and improved islet transplant outcome. CONCLUSIONS/INTERPRETATION: These findings suggest that control of the JNK pathway is extremely important in islet transplantation and that intraportal injection of JNK inhibitor during islet transplantation (addition of JNK inhibitor to transplant media) could prevent the impairment of islet cells, leading to improved outcome for pancreatic islet transplantation.

Vacuum ultraviolet spectroscopy of Ce(3+)-doped SrMgF(4) with superlattice structure.

X-ray diffraction of Ce(3+)-doped SrMgF(4) (SMF:Ce) crystals shows a superlattice structure, reflecting the distribution of Ce(3+) polyhedra centres observed in optical experiments. Optical absorption bands and fluorescence bands from the Ce(3+) polyhedra centres overlap in the vacuum ultraviolet (VUV) and ultraviolet (UV) regions, respectively, so that wide pumping and tuning ranges are expected for laser operation. The SMF:Ce crystals, as well as the isomorphous BaMgF(4), are candidates for a tunable laser gain material with nonlinear properties. The optical absorption, excitation, and fluorescence bands observed in the SMF:Ce crystals at low temperatures are ascribed to five distinct fluorescent centres. Three centres have well-known Ce(3+) optical characters, for example, fluorescence with double peaks separated by 2000 cm(-1) and five resolved absorption/excitation bands. These centres are assigned to Ce(3+)-polyhedra classified by weak and strong crystal fields as a consequence of the superlattice structure. The other two fluorescence bands observed in the visible region have 1.5-2 times larger linewidths than those of the former three bands. These bands are interpreted as optical transitions from complexes consisting of Ce(3+) and one or two electrons trapped at a vacancy of the nearest neighbour F(-) ligand ions.

Do personality characteristics predict longevity? Findings from the Tokyo Centenarian Study.

To explore whether personality influences longevity we examined the personality characteristics of centenarians. We developed a new method that compares an actual personality test score for centenarians with a predicted test score for a 100-year-old, calculated from younger controls. The participants consisted of 70 cognitively intact Japanese centenarians aged 100-106 years and 1812 elderly people aged 60-84 years, all residents of Tokyo. The NEO five factor inventory (NEO-FFI) was used to assess the "big five" personality traits: neuroticism, extraversion, openness, agreeableness, and conscientiousness. The results showed higher openness in both male and female centenarians, and higher conscientiousness and extraversion in female centenarians, as compared to controls. These results suggest that high scores in the specific personality traits conscientiousness, extraversion, and openness, are associated with longevity. We speculate that these personality traits contribute to longevity through health-related behavior, stress reduction, and adaptation to the challenging problems of the "oldest old".

Noninvasive estimation of cardiac systolic function using continuous-wave Doppler echocardiography in dogs with experimental mitral regurgitation.

OBJECTIVE: To evaluate the feasibility of noninvasive estimation of cardiac systolic function using transthoracic continuous-wave Doppler echocardiography in dogs with mitral regurgitation. PROCEDURE: Seven mongrel dogs with experimental mitral regurgitation were used. Left ventriculography and measurement of pulmonary capillary wedge pressure were performed under inhalational anaesthesia. A micromanometer-tipped catheter was placed into the left ventricle and transthoracic echocardiography was carried out. The peak rate of left ventricular pressure rise (peak dP/dt) was derived simultaneously by continuous-wave Doppler and manometer measurements. The Doppler-derived dP/dt was compared with the catheter-measured peak dP/dt in the dogs. RESULTS: Classification of the severity of mitral regurgitation in the dogs was as follows: 1+, 2 dogs; 2+, 1 dog; 3+, 2 dogs; 4+, 1 dog; and not examined, 1 dog. We were able to derive dP/dt from the transthoracic continuous-wave Doppler echocardiography in all dogs. Doppler-derived dP/dt had a significant correlation with the catheter-measured peak dP/dt (r = 0.90, P < 0.0001). CONCLUSION: It was demonstrated that transthoracic continuous-wave Doppler echocardiography is a feasible method of noninvasive estimation of cardiac systolic function in dogs with experimental mitral regurgitation and may have clinical usefulness in canine patients with spontaneous mitral regurgitation.

Interleukin-1beta enhances retinoic acid-mediated expression of bone-type alkaline phosphatase in rat IEC-6 cells.

We previously showed that vitamin A upregulated the expression of bone-type alkaline phosphatase (ALP) in fetal rat small intestine and rat intestinal IEC-6 cells. In this study, we examined interactions between retinoic acid (RA) and several growth factors/cytokines on the isozyme expression in IEC-6 cells. Epidermal growth factor and interleukins (ILs)-2, -4, -5, and -6 completely blocked the RA-mediated increase in ALP activity. In contrast, IL-1beta markedly increased the activity, protein, and mRNA of the bone-type ALP only when RA was present. IL-1beta and/or RA did not change the type 1 IL-1 receptor transcript level, whereas IL-1beta enhanced the RA-induced expressions of retinoic acid receptor-beta (RAR-beta) and retinoid X receptor-beta (RXR-beta) mRNAs and RA-mediated RXR response element binding. The synergism of IL-1beta and RA on ALP activity was completely blocked by protein kinase C (PKC) inhibitors. Our results suggest that IL-1beta may modify the ALP isozyme expression in small intestinal epithelial cells by stimulating PKC-dependent, RAR-beta- and/or RXR-beta-mediated signaling pathways.

Activation of NF kappa B and expression of ICAM-1 in ischemic-reperfused canine myocardium.

Although redox-sensitive transcription factors, including nuclear factor kappa B (NF kappa B) and activator protein-1 (AP-1), have been shown to induce intercellular adhesion molecule-1 (ICAM-1) gene transcription in isolated cells, little is known about their involvement in the regulation of the ICAM-1 gene in vivo during ischemia-reperfusion. Anesthetized closed-chest dogs underwent 90 min coronary artery occlusion, followed by reperfusion for 0, 15, 30, 60, 180, or 360 min. Blood flow (fluorescent or radioactive microspheres), ICAM-1 protein expression (immunohistochemistry), ICAM-1 gene activation (Northern blotting), and nuclear DNA-binding activity of NF kappa B and AP-1 (electrophoretic mobility shift assays) were assessed in myocardial tissue samples. ICAM-1 protein was expressed constitutively on vascular endothelium, but expression levels decreased markedly during ischemia. Within 15 min reperfusion, endothelial ICAM-1 protein increased, associated with a rapid appearance of ICAM-1 mRNA. Activation of both NF kappa B and AP-1 occurred following ischemia-reperfusion, but did not coincide temporally with early post-reperfusion ICAM-1 gene induction. NF kappa B was activated during ischemia, when ICAM-1 mRNA was undetectable, and did not increase further until 60 min reperfusion, well after the increase in ICAM-1 mRNA had begun. Similarly, AP-1 did not increase until 60 min reperfusion. In non-ischemic myocardium, NF kappa B and AP-1 were both activated, but ICAM-1 mRNA did not appear until 6 h later. By immunohistology, NF kappa B (p65 subunit) and the c-Fos subunit of AP-1 were localized primarily in vascular endothelium. Reperfusion of ischemic myocardium is associated with very rapid ICAM-1 gene induction in the context of prior NF kappa B activation, without new activation of NF kappa B. In non-ischemic myocardium, ICAM-1 transcription begins hours after NF kappa B is activated. These findings support a role for NF kappa B in ICAM-1 induction in vivo, but suggest that other processes, such as oxygen-radical generation, may combine with NF kappa B to trigger an accelerated transcription of ICAM-1 following ischemia-reperfusion.

From oocyte maturation to the in vitro cell cycle: the history of discoveries of Maturation-Promoting Factor (MPF) and Cytostatic Factor (CSF).

This article briefly reviews the classical cell cycle studies using oocytes and zygotes of mainly amphibians in the past century. The discussions are focused on the investigations into the cytoplasmic factors that regulate meiosis during oocyte maturation and the initiation of mitosis during fertilisation, which were carried out in the author's lab between 1967 and 1987. This chronicle traces the development of the problems and the direction in which their solutions were attempted in the course of these investigations. The author tries to answer the following questions: why he decided to study oocyte maturation, how he discovered progesterone as a maturation-inducing hormone, how he discovered and characterised the cytoplasmic regulators of the cell cycle, Maturation-Promoting Factor (MPF) and Cyto-Static Factor (CSF), and how he invented the method of observing cell cycle processes in a cytoplasmic extract in vitro.