Association of Dietary Intake with the Transitions of Frailty among JapaneseCommunity-Dwelling Older Adults.

BACKGROUND: Frailty is a dynamic process, with frequent transitions between frailty, prefrailty, and robust statuses over time. The effect of dietary intake on frailty transitions is unknown. OBJECTIVE: To examine the association between dietary intake and frailty transitions. DESIGN: Survey-based retrospective analysis of the National Institute for Longevity Sciences-Longitudinal Study of Aging data. SETTING: Areas neighboring the National Center for Geriatrics and Gerontology in Aichi Prefecture, Japan. PARTICIPANTS: We included 469 prefrail community dwellers aged 60-87 years who participated both in the baseline (2008-2010) and 2-year follow-up (2010-2012) surveys of the National Institute for Longevity Sciences-Longitudinal Study of Aging. MEASUREMENTS: Transitions of frailty were categorized by changes in status from baseline to follow-up: "deterioration (prefrail to frail)," "persistence (persistent prefrail)," and "reversal (prefrail to robust)." Estimated dietary (nutrients and food) intakes assessed by 3-day dietary records in each frailty transition were analyzed with a multivariate-adjusted general linear model after adjusting for sex, age, education, family income, smoking, and chronic disease. RESULTS: At the 2-year follow-up, 28%, 7%, and 65% of participants had robust, frail, and pre-frail status, respectively. Among 13 food groups, only milk and dairy product intake was positively associated with frailty reversal even after adjusting for all frailty criteria at baseline. Despite insignificant differences in the estimated mean intakes, the baseline intake of saturated fatty acids, potassium, and vitamin B1 tended to be the highest in the reversal group. The estimated mean (standard error) for milk and dairy product intake (g/day) was 79.1 (28.6), 129.3 (19.9), and 161.7 (21.7) for the deterioration, persistence, and reversal groups, respectively (P=0.0036, P-trend=0.0019). CONCLUSIONS: Daily consumption of dairy products may contribute to frailty reversal and frailty prevention among older community dwellers who consume small amounts of dairy products. Other food groups showed no association with frailty status transitions.

Low Amino Acid Score of Breakfast is Associated with the Incidence of Cognitive Impairment in Older Japanese Adults: A Community-Based Longitudinal Study.

BACKGROUND: The protein digestibility-corrected amino acid score (PDCAAS) represents the degree of utilizable dietary protein, namely the protein quality. The PDCAAS of a diet is required to be evaluated on a meal-by-meal basis, as food digestion and absorption occur with each meal intake. Although a positive association between protein intake and cognitive function has been reported, no study has investigated the association between PDCAAS of a diet and cognitive function. OBJECTIVES: To investigate the relationship between PDCAAS of a diet and cognitive impairment in older adults. DESIGN: Longitudinal epidemiological study. SETTING: Community-based setting. PARTICIPANTS: We analyzed 541 community-dwellers who participated in both baseline and follow-up survey. They were 60-83 years of age without cognitive impairment at baseline. MEASUREMENTS: Cognitive impairment was defined as a Mini-Mental State Examination (MMSE) score ≤27. Individual PDCAASs were calculated for each of three regular meals from the 3-day dietary records at baseline. Participants were classified into two groups according to the sex-specific tertiles (T1-T3) of the PDCAAS for each meal (i.e., T1 as the low score group and T2-T3 as the medium and high score group). The dependent variable was cognitive impairment observed after 4 years, and the explanatory variables were the PDCAAS groups for each meal (the medium and high group as the reference) and covariates (sex, age, body mass index, education, depressive symptoms, medical history, protein intake at each meal, and the MMSE score at baseline). Multivariable logistic regression analysis was performed to evaluate the low PDCAAS group for cognitive impairment after 4 years. RESULTS: A significant association was observed only between a low PDCAAS of breakfast and the incidence of cognitive impairment (the adjusted odds ratios [95% confidence intervals] of low PDCAAS for cognitive impairment for breakfast, lunch, and dinner were 1.58 [1.00-2.50], 0.85 [0.54-1.34], and 1.08 [0.71-1.65], respectively). CONCLUSION: A lower PDCAAS of breakfast, i.e., a diet with poor quality of protein, was associated with the incidence of cognitive impairment in older adults of the community.

Commercial ChIP-Seq Library Preparation Kits Performed Differently for Different Classes of Protein Targets.

Background: Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) is a powerful method commonly used to study global protein-DNA interactions including both transcription factors and histone modifications. We have found that the choice of ChIP-Seq library preparation protocol plays an important role in overall ChIP-Seq data quality. However, very few studies have compared ChIP-Seq libraries prepared by different protocols using multiple targets and a broad range of input DNA levels. Results: In this study, we evaluated the performance of 4 ChIP-Seq library preparation protocols (New England Biolabs [NEB] NEBNext Ultra II, Roche KAPA HyperPrep, Diagenode MicroPlex, and Bioo [now PerkinElmer] NEXTflex) on 3 target proteins, chosen to represent the 3 typical signal enrichment patterns in ChIP-Seq experiments: sharp peaks (H3K4me3), broad domains (H3K27me3), and punctate peaks with a protein binding motif (CTCF). We also tested a broad range of different input DNA levels from 0.10 to 10 ng for H3K4me3 and H3K27me3 experiments. Conclusions: Our results suggest that the NEB protocol may be better for preparing H3K4me3 (and potentially other histone modifications with sharp peak enrichment) libraries; the Bioo protocol may be better for preparing H3K27me3 (and potentially other histone modifications with broad domain enrichment) libraries, and the Diagenode protocol may be better for preparing CTCF (and potentially other transcription factors with well-defined binding motifs) libraries.  For ChIP-Seq experiments using novel targets without a known signal enrichment pattern, the NEB protocol might be the best choice, as it performed well for each of the 3 targets we tested across a wide array of input DNA levels.

Relationship between Serum Fatty Acids and Components of Physical Frailty in Community-Dwelling Japanese Older Adults.

Polyunsaturated fatty acids help maintain insulin sensitivity, mitochondrial function, and anti-inflammation. It is well known that deterioration in these areas can cause frailty. However, little is known about the differences in serum polyunsaturated fatty acid levels among frailty components. We investigated the cross-sectional relationship between frailty and serum fatty acids in 1,033 community-dwelling older adults aged 60-88 years. Polyunsaturated fatty acid concentrations were measured from fasting blood samples. The modified phenotype criteria defined frailty. Polyunsaturated fatty acid levels were compared among each component using general linear modeling after controlling for sex, age, body mass index, smoking status, household income, and medical history. Lower polyunsaturated fatty acid levels were associated with the modified frailty criteria, including shrinking and weakness (p < 0.05). Our findings suggest that serum polyunsaturated fatty acid levels differ depending on the frailty status of older adults.

The Association between Dietary Amino Acid Intake and Cognitive Decline 8 Years Later in Japanese Community-Dwelling Older Adults.

OBJECTIVES: Previous studies have reported a relationship between low protein intake and cognitive decline and have suggested that this association may be related to specific amino acid intake. However, the effects of amino acid intake on the maintenance of cognitive function have yet to be clarified. We examined the longitudinal association between dietary amino acid intake and cognitive function in community-dwelling older adults. DESIGN: Longitudinal epidemiological study. SETTING: Community-based setting. PARTICIPANTS: This study comprised 427 study participants aged 60-82 years with no cognitive decline, defined as a Mini-Mental State Examination (MMSE) score of >27 at baseline, who also participated in a follow-up. The average and standard deviation of the follow-up period was 8.2 ± 0.3 years. MEASUREMENTS: Dietary intake was assessed using three-day dietary records at baseline. Participants were classified into quartiles (Q1-Q4) based on the intake of 19 amino acids for males and females. Next, we classified participants into Q1 and Q2-Q4 groups. Cognitive function was assessed using the MMSE both at baseline and at follow-up. Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between the Q1 group and cognitive decline (MMSE ≤27), using the Q2-Q4 group as a reference group. Covariates were age, sex, body mass index, years of education, severity of depressive symptoms, history of lifestyle diseases (hypertension, dyslipidemia, diabetes mellitus, stroke, and ischemic heart disease), energy intake (kcal/d), protein intake (g/d), and MMSE score at baseline. RESULTS: Cognitive decline was present in 133 (31.1%) participants. After adjustment for covariates, including total protein intake, the ORs (95% CIs) for cognitive decline were 2.40 (1.21-4.75) for lysine, 2.05 (1.02-4.09) for phenylalanine, 2.18 (1.09-4.34) for threonine, and 2.10 (1.06-4.15) for alanine. CONCLUSION: The results suggest that lysine, phenylalanine, threonine, and alanine intake is important for the maintenance of cognitive function in older people, independent of total protein intake.

Association of Muscle Strength and Gait Speed with Cross-Sectional Muscle Area Determined by Mid-Thigh Computed Tomography - A Comparison with Skeletal Muscle Mass Measured by Dual-Energy X-Ray Absorptiometry.

BACKGROUND: Muscle mass is often mentioned not to reflect muscle strength. For muscle mass assessment skeletal muscle index (SMI) is often used. We have reported that dual-energy X-ray absorptiometry (DXA)-derived SMI does not change with age in women, whereas the cross-sectional muscle area (CSMA) derived from computed tomography (CT) does. OBJECTIVES: The present study aimed to compare CT and DXA for the assessment of muscle tissue. DESIGN AND SETTING: Cross-sectional study in the local residents. PARTICIPANTS: A total of 1818 subjects (age 40-89 years) randomly selected from community dwellers underwent CT examination of the right mid-thigh to measure the cross-sectional muscle area (CSMA). Skeletal muscle mass (SMM) was measured by DXA. The subjects performed physical function tests such as grip strength, knee extension strength, leg extension strength, and gait speed. The correlation between CT-derived CSMA and DXA-derived SMM along with their association with physical function was examined. RESULTS: After controlling for related factors, the partial correlation coefficient of muscle cross-sectional area (CSA) with physical function was larger than that of DXA-derived SMM for gait speed in men (p=0.002) and knee extension strength in women (p=0.03). The partial correlation coefficient of quadriceps (Qc) CSA with physical function was larger than that of DXA-derived SMM for leg extension power in both sexes (p=0.01), gait speed in men (p<0.001), and knee extension strength in women (p<0.001). CONCLUSION: Mid-thigh CT-derived CSMA, especially Qc CSA, showed significant associations with grip strength, knee extension strength, and leg extension power, which were equal to or stronger than those of DXA-derived SMM in community-dwelling middle-aged and older Japanese people. The mid-thigh CSMA may be a predictor of mobility disability, and is considered to be useful in the diagnosis of sarcopenia.

Dietary factors associated with the development of physical frailty in community-dwelling older adults.

OBJECTIVES: Nutrition plays an important role in the development of frailty, and the present study examined the association between energy, macronutrient, and food intake and the development of physical frailty. DESIGN: Prospective cohort study. SETTING: The National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA), a community-based study. PARTICIPANTS: Participants included 166 men and 117 women aged 65-86 years without frailty components at baseline who participated in both the sixth (2008-2010) and seventh (2010-2012) waves of the NILS-LSA. MEASUREMENTS: Physical frailty was assessed using the modified criteria established by the Cardiovascular Health Study (2001). All participants were classified as "robust (number of frailty components: 0)," "prefrail (1-2)," or "frail (3-5)." Energy, macronutrient, and food intake was calculated based on 3-day dietary records during the sixth wave. Associations between dietary intake per day and the development of frailty 2 years later (from robust at the sixth wave to prefrail/frail at the seventh wave) were examined using multiple logistic regression analysis after adjusting for sex, baseline age, and other covariables. RESULTS: Among the participants included, 36% were classified as prefrail/frail 2 years later. Higher energy [1 standard deviation (SD), odds ratio (95% confidence interval): 362 kcal, 0.68 (0.49-0.94)], protein [16 g, 0.72 (0.53-0.97)], and fat [15 g, 0.69 (0.52-0.92)] intake was negatively associated with frailty development. Higher meat [38 g, 0.68 (0.51-0.92)] and dairy [114 g, 0.73 (0.55-0.96)] intake was negatively associated with frailty development. Higher energy intake was negatively associated with the development of weakness (low grip strength) and low activity, while higher protein intake was negatively associated with the development of low activity. CONCLUSION: Increased consumption of meat and dairy products may provide sufficient protein and fat necessary for achieving higher energy intake, thereby effectively preventing physical frailty among older Japanese individuals.

Age-Related 12-Year Changes in Dietary Diversity and Food Intakes among Community-Dwelling Japanese Aged 40 to 79 Years.

OBJECTIVES: This study describes trends in dietary diversity and food intake over 12 years according to age at first participation in the study. DESIGN: Prospective cohort study. SETTING: The National Institute for Longevity Sciences - Longitudinal Study of Aging, a community-based study. PARTICIPANTS: Participants included 922 men and 879 women who participated in the first study-wave (age, 40-79 years) and also participated in at least one study-wave from the second to seventh study-wave. Study-waves were conducted biennially. MEASUREMENTS: Dietary intake was calculated from 3-day dietary records with photographs. Dietary diversity was determined using the Quantitative Index for Dietary Diversity based on food intake. A mixed-effects model was used to estimate linear changes in dietary diversity and food intake over 12 years according to age at first study-wave. RESULTS: Mean (standard deviation (SD)) follow-up time and number of study-wave visits were 9.5 (3.7) years and 5.4 (1.8), respectively. Mean (SD, range) dietary diversity score was 0.86 (0.06, 0.52-0.96) in men and 0.88 (0.04, 0.66-0.96) in women, respectively. Fixed effects for interactions of age and time with dietary diversity score were statistically significant (p<0.05). The slope of dietary diversity among men aged 40 to 55 years increased (40-year-old slope = 0.00093/year, p<0.01; 55-year-old slope = 0.00035/year, p=0.04), with a decreasing trend started at 65 years old, although this trend was not significant (65-year-old slope = -0.00003/year, p=0.88; 79-year-old slope = -0.00057/year, p=0.21). The slope of dietary diversity among women aged 40 to 44 years increased (40-year-old slope = 0.00053/year, p=0.02; 44-year-old slope = 0.00038/year, p=0.04), whereas the slope of dietary diversity among women aged 63 to 79 years decreased (63-year-old slope = -0.00033/year, p=0.03; 79-year-old slope = -0.00092/year, p<0.001). Fruit, milk and dairy intake decreased in men around their 60s; milk and dairy intake decreased in women around their 50s; and beans and fruit intake decreased in women from their 70s. CONCLUSION: Twelve-year longitudinal data showed dietary diversity declined in women in their 60s. In terms of food intake, fruit, milk and dairy intake decreased in both sexes in their 50s and 60s; such declines would lower dietary diversity.

Age-related Changes in Energy Intake and Weight in Community-dwelling Middle-aged and Elderly Japanese.

OBJECTIVE: This study attempts to describe trends in energy intake and weight change over 12 years according to age at first participation in the study. DESIGN: Prospective cohort study. SETTING: The National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA), a community-based study. PARTICIPANTS: Participants included 922 men and 879 women who participated in the first study-wave (age 40-79 years) and also participated in at least one study-wave from the second to seventh study-wave. Each study-wave was conducted biennially. For individuals, the entire follow-up period was 12 years. MEASUREMENTS: Energy intake was calculated from 3-day dietary records with photographs. Weight and height were measured under a fasting state. To estimate linear changes in energy intake and weight over 12 years according to age at first study-wave, we used the mixed-effects model. RESULTS: Mean (SD) follow-up time and number of study-wave visits were 9.5 (3.7) years and 5.4 (1.8) times, respectively. The fixed effect of the interaction of age and time in energy intake and weight was statistically or marginally statistically significant both in men (p<0.01) and in women (p<0.06). In men, when energy intake was estimated according to age, the rate of decrease in energy intake increased from -6.8 to -33.8 kcal/year for ages 40-79 years. In women, the rate of decrease in energy intake slightly increased in older age groups (-9.1 to -16.7 kcal/year for ages 40-79 years). Weight increased in males in their 40s (0.07 kg/year from age 40) and started to decline by age 53. In women, weight started to decline around age 47 (-0.04 kg/year). CONCLUSION: Twelve-year longitudinal data showed energy intake declined both in men and women in their 40s, and the rate of decrease increased in older males. Weight started to decline in men in their mid-50s and women in their late 40s. Further studies that focus on energy intake and weight reduction are needed to prevent weight loss or underweight in an increasingly aging society.

Cereal Intake Increases and Dairy Products Decrease Risk of Cognitive Decline among Elderly Female Japanese.

BACKGROUND: If cognitive decline can be prevented through changes in daily diet with no medical intervention, it will be highly significant for dementia prevention. OBJECTIVES: This longitudinal study examined the associations of different food intakes on cognitive decline among Japanese subjects. DESIGN: Prospective cohort study. SETTING: The National Institute for Longevity Sciences - Longitudinal Study of Aging, a community-based study. PARTICIPANTS: Participants included 298 males and 272 females aged 60 to 81 years at baseline who participated in the follow-up study (third to seventh wave) at least one time. MEASUREMENTS: Cognitive function was assessed with the Mini-Mental State Examination (MMSE) in all study waves. Nutritional intake was assessed using a 3-day dietary record in the second wave. Cumulative data among participants with an MMSE >27 in the second wave were analyzed using a generalized estimating equation. Multivariate adjusted odds ratios (OR) and 95% confidence intervals (CI) for an MMSE score ≤27 in each study wave according to a 1 standard deviation (SD) increase of each food intake at baseline were estimated, after adjusting for age, follow-up time, MMSE score at baseline, education, body mass index, annual household income, current smoking status, energy intake, and history of diseases. RESULTS: In men, after adjusting for age, and follow-up period, MMSE score at baseline, the adjusted OR for a decline in MMSE score was 1.20 (95% CI, 1.02-1.42; p=0.032) with a 1-SD increase in cereal intake. After adjusting for education and other confounding variables, the OR for a decrease in MMSE score did not reach statistical significance for this variable. In women, multivariate adjusted OR for MMSE decline was 1.43 (95% CI, 1.15-1.77; p=0.001) with a 1-SD increase in cereal intake and 0.80 (95% CI, 0.65-0.98; p=0.034) with a 1-SD increase in milk and dairy product intake. CONCLUSIONS: This study indicates that a 1-SD (108 g/day) decrease in cereal intake and a 1-SD (128 g/day) increase in milk and dairy product intake may have an influence of cognitive decline in community-dwelling Japanese women aged 60 years and older. Further studies are needed in order to explore the potential causal relationship.

Histopathological safety evaluation of newly-developed MgO sealer.

We aimed to evaluate the subcutaneous tissue reaction to a newly-developed MgO Sealer for root canals. We injected the experimental material and three existing control materials into the dorsal area of 43 male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embedding sites was removed and histopathological examination was performed. The results demonstrate that the basic histopathological reaction is the formation of fibrous capsules consisting of granulation tissue around the experimental and control embedded materials. Based on our results, we believe that the newly-developed MgO Sealer is as safe as the existing control materials and can be considered for dental use as a root canal sealer.

Notch signaling and ghost cell fate in the calcifying cystic odontogenic tumor.

Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs) are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites). Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (CCOT), their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4) and three ligands (Jagged1, Jagged2 and Delta1) was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0), mild (+), moderate (2+) and strong (3+). Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1-Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.

Strawberry gingivitis as the first presenting sign of Wegener's granulomatosis: report of a case.

Wegener's granulomatosis is a rare multi-system disease characterized by the classic triad of necrotizing granulomas affecting the upper and lower respiratory tracts, disseminated vasculitis and glomerulonephritis. Oral lesions as a presenting feature are only encountered in 2% of these cases. Hyperplastic gingival lesions or strawberry gingivitis, is a characteristic sign of Wegener's granulomatosis. The latter consists of reddish-purple exophytic gingival swellings with petechial haemorrhages thus resembling strawberries. Recognition of this feature is of utmost importance for timely diagnosis and definitive management of this potentially fatal disease. A case of strawberry gingivitis as the first presenting sign of Wegener's granulomatosis affecting a 50-year-old Malay male is reported here. The differential diagnosis of red lesions that may present in the gingiva is discussed.

Comparative examination of subcutaneous tissue reaction to high molecular materials in medical use.

Polypropylene (PP), Polyethylene (PE) and polytetrafluoroethylene (FE) are high molecular materials in medical use. They are also used as the negative control materials for ISO 10993-6 international standard biological evaluation of medical devices. We examined tissue reactions to these materials embedded subcutaneously in the dorsal area of male ddY mice. One week and 12 weeks after embedding, the tissue surrounding the embedding site was removed and then histopathological examination was performed. Our results demonstrate that the basic histopathological reaction is the formation of fibrous capsule consisting of granulation tissue around the embedded materials. Based on our results, we believe that the high molecular materials such as, PP, PE and FE, can be considered for medical use as a biomaterials within the body.

Squamous odontogenic tumor of the mandible: a case report demonstrating immunoexpression of Notch1, 3, 4, Jagged1 and Delta1.

BACKGROUND: Squamous odontogenic tumor (SOT) is a rare benign odontogenic epithelial neoplasm. A slow-growing painless expansive swelling is the common presenting symptom. Histopathologically, SOT can be easily misdiagnosed as an acanthomatous ameloblastoma. Although Notch receptors and ligands have been shown to play a role in cell fate decisions in ameloblastomas, the role of these cell signaling molecules in SOT is unknown. CASE REPORT: This paper describes a case of SOT affecting the anterior mandible of a 10-year-old Indian female. The patient was treated by local surgical excision and there has been no follow-up clinical record of recurrence 5 years after primary treatment. Histo?pathological examination revealed a solid, locally-infiltrative neoplasm composed of bland-looking squamatoid islands scattered in a mature fibrous connective tissue stroma and the diagnosis was SOT. Immunohistochemical evaluation showed positive reactivity of varying intensity in the neoplastic epithelial cells for Notch1, Notch3, Notch4, and their ligands Jagged1 and Delta1. Expression patterns showed considerable overlap. No immunoreactivity was detected for Notch2 and Jagged2. CONCLUSIONS: Present findings suggest that Notch receptors and their ligands play differential roles in the cytodifferentiation of SOT.

Influence of changing the chewing region on mandibular movement.

BACKGROUND: In the shortened dental arch condition, little is known of how patients adapt their jaw function during mastication to the new oral environment. This study aimed to investigate the changes in mandibular movements when the chewing region was changed from the first molar to the first premolar. METHODS: Thirty clinical residents with natural dentitions were recruited. The subjects were asked to chew a piece of beef jerky using either the first molar or the first premolar on the preferred chewing side. Three-dimensional trajectories of lower incisors and both condyles were analysed using a jaw movement tracking device with six degrees of freedom during the period between the onset and offset of electromyographic bursts from the masseter and anterior temporal muscles. RESULTS: The closing angle of the lower incisors for first premolar chewing was narrower in comparison with that for first molar chewing (p < 0.05). The lengths of the condylar trajectories and the maximum velocities of the condylar movement for first premolar chewing were smaller and slower, respectively, in comparison with those for first molar chewing (both sides; p < 0.01). CONCLUSIONS: The mandibular movement during mastication might be changed to adapt the premolar chewing because of a loss of posterior occlusal supports.

Multistep differentiation of GH-producing cells from their immature cells.

In order to study GH cell differentiation, we used the clonal cell lines called MtT/E and MtT/S cells, which were derived from a rat mammotrophic pituitary tumor. Although MtT/E cells are non-hormone-producing ones, Pit-1 protein is present in their nuclei, which suggests that MtT/E cells are progenitor cells of the Pit-1 cell lineage and have the potential to differentiate into hormone-producing cells. On the other hand, MtT/S cells produce GH; however, the responsiveness to GH-releasing hormone (GHRH) is weak and only a small number of secretory granules are present in their cytoplasm, which suggests that MtT/S cells are premature GH cells. In order to differentiate into GH cells from MtT/E cells as a progenitor cell, we examined several differentiation factors and found that retinoic acid (RA) induced the differentiation of MtT/E cells into GH-producing cells. RA-induced GH cells partially matured with the glucocorticoid treatment; however, the responsiveness to GHRH on GH secretion was incomplete. In order to elucidate the mechanism underlying full differentiation of GH cells, we used MtT/S cells. We treated MtT/S cells with glucocorticoid and found that they differentiated into mature GH cells with many secretory granules in their cytoplasm and they responded well to GHRH. These results suggested that MtT/E and MtT/S cells are progenitor or premature GH cells, and show different responses to differentiation factors. Our data also suggested that GH cells differentiate from their progenitor cells through multistep processes.

Intra-articular oxidative state correlated with the pathogenesis of disorders of the temporomandibular joint.

We investigated the redox state of albumin in the synovial fluid from patients with temporomandibular joint (TMJ) disorders (TMD) to evaluate the relation between the cause of the TMD and the number of types of oxygen in synovial fluid. The albumin was fractionated into three components, human mercaptalbumin (HMA, reduced form) and two types human non-mercaptalbumin (HNA, oxidized form), by high-performance liquid chromatography (HPLC). The 63 patients were divided into three groups radiologically, and the ratios of the redox state of the synovial fluid in each group were compared. The fraction of HNA was significantly higher in patients with advanced disease than in patients with early disease. This indicates that the TMJ is affected by intra-articlular oxidative stress, and the severity of TMD correlates closely with the number of oxidative factors. Oxidative stress was thought to be responsible for the genesis of TMD.

Response durations encode nociceptive stimulus intensity in the rat medial prefrontal cortex.

We examined whether the medial prefrontal cortex (mPFC) encodes nociceptive stimulus intensity by applying mechanical pressure stimulation, for 2 s at 50, 100, or 300 g constant force (gf) to the tails of urethane-anesthetized rats. In a total of 1208 neurons sampled, 242 (20.0%) were responsive to mechanical stimuli. One hundred thirteen of the 242 (46.7%) were mechanical high threshold neurons (nociceptive specific neurons, NS; threshold >or=100 gf), and 35 (14.5%) exhibited a graded increase in excitator responses to a stepwise increase in stimulus intensity (wide dynamic range-like neurons, WDR-L). These 148 response discharges persisted during stimulation followed by post-stimulus discharges. The nociceptive response duration of NS neurons, but not discharge frequency, was reduced dose-dependently by intraventricular injection of morphine (0.3, and 30 microg/3 microl). Different doses of morphine may set the stimulus intensity at relatively different brain activity levels. Thus, the NS neurons used the response duration as a sensory transduction code. In WDR-L neurons, the response duration, but not always the firing frequency, was linearly related to stimulus intensity. The WDR-L neurons in the mPFC encoded stimulus intensity with response duration, although the coding method is not likely to be the same as that of sensory discriminating WDR cells in the primary somatosensory cortex. Both types of mPFC neurons encode nociceptive (absolute or relative) stimulus intensity and transform the information into the temporal duration of the next stage of pain-related modulation in animal behavior.

Augmentation of monocyte interleukin-8 production by psoralen/UVA-treated CD4+ T cells.

Treatment of cells with psoralen and ultraviolet A light (UVA) modulates their cytokine production. As extracorporeal photochemotherapy has been reported to induce cytokine production by monocytes, we quantified interleukin-8 (IL-8), a representative chemokine produced by monocytes, in culture supernatants from human peripheral blood mononuclear cells (PBMC) treated with 8-methoxypsoralen (8-MOP) and UVA. Lipopolysaccharide stimulated IL-8 production in 8-MOP-phototreated PBMC more efficiently than those untreated or treated with 8-MOP or UVA. More interestingly, when cultured with T-cell-stimulating anti-CD3 and anti-CD28 antibodies, 8-MOP/UVA-treated PBMC produced enhanced amounts of IL-8 with an increased level of IL-8 mRNA expression. Depletion of CD4 but not CD8 T cells from PBMC abrogated this augmented IL-8 elaboration, and CD4 T cells per se secreted no substantial amount of IL-8 even upon CD3/CD28 stimulation. Thus, 8-MOP/UVA-treated CD4 T cells stimulated monocytes to secrete IL-8. The IL-8 overproduction was induced by direct contact of monocytes with 8-MOP/UVA-treated CD4 T cells but not by cytokines from the treated CD4 T cells. These findings imply that in extracorporeal photochemotherapy, monocytes effectively produce IL-8 by cell-to-cell contact with 8-MOP/UVA-treated malignant CD4 T cells. The augmentation of monocyte cytokine/chemokine production by 8-MOP/UVA may be one of the mechanisms underlying the therapeutic efficacy of extracorporeal photochemotherapy.