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Autoimmune-prone mice homozygous for the 1pr gene develop prominent lymphadenopathy composed mainly of Thy-1+ CD8- CD4- B220+ cells. Expression patterns of B220vsCD4 on lymph node cells from 1pr mice were analysed using two-colour flow microfluorometry. B220+CD4+ cells, which were hardly seen in lymph nodes of B6-+ / + mice, increased significantly in B6-lpr mice with ageing. Functional analysis of purified B220+ CD4+ cells from 1pr mice revealed that these cells scarcely responded to T cell mitogens with or without rIL-2. Furthermore, B220+ CD4+ cells were defective in IL-2 production when cultured with Con A. On the other hand, B220-CD4+ cells from B6-lpr mice showed an ability to respond to T cell mitogens similar to that of B220- CD4+ cells from B6-+/+ mice. These results indicate that an unusual T cell subset expressing both B220 and CD4 in 1pr mice is functionally defective, but the intrinsic ability of B220- CD4+ cells is almost intact as compared with the counterpart in normal mice. [ABSTRACT FROM AUTHOR]

Background: Increase in functional disability in aging societies is an international medical and public health issue. Masticatory function may be a potential risk factor for functional disability, but the role of frailty in the association has not been clarified., Methods: Forty thousand five hundred sixty-two community-dwelling older adults aged 65 years and over who were insured by public health insurance as of April 2018 were followed up for a median of 3.0 years. Masticatory function was categorized as good, moderate, or poor based on a self-reported questionnaire. The development of functional disability was defined as a new certification of the need for long-term care. A Cox proportional hazards model was used to calculate hazard ratios (HRs) and their 95% confidence intervals (CIs)., Results: During the follow-up period, 1,397 individuals experienced functional disability. After adjusting for age, sex, comorbidities, medical history, and lifestyle behaviors, the HR for incident functional disability was significantly higher in the moderate and poor groups compared to the good group (moderate, HR 1.21 [95% CI, 1.07-1.37]; poor, HR 1.64 [95% CI, 1.03-2.62]). However, after additional adjustment for frailty-related factors-namely, underweight, regular exercise, and gait speed-the association was attenuated in both the moderate group (HR 1.06 [95% CI, 0.94-1.21]) and the poor group (HR 1.51 [95% CI, 0.94-2.41])., Conclusions: Masticatory dysfunction was significantly associated with incident functional disability in a community-dwelling older Japanese population. Our findings suggest that masticatory dysfunction may be a surrogate of frailty rather than a direct cause of functional disability., (© 2024. The Author(s).)

Background: The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population., Methods: 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002-2003 were followed up by repeated examination in 2007-2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1-4: 2.20-9.56, 9.57-10.78, 10.79-12.18, and 12.19-24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model., Results: At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1-4: 1.00 [reference], 2.92 [1.59-5.37], 3.48 [1.91-6.35], and 3.86 [2.12-7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend = 0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend = 0.07)., Conclusion: In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.

Background: The Fukuoka-City Information Platform for Community-based Integrated Care is an advanced big data platform that aggregates information on the health and medical services of Fukuoka citizens. Fukuoka City is engaged in a joint project with Kyushu University to promote policy making through a large-scale real-world data analysis. This paper describes the framework for this cooperative effort and the features of the analytical platform., Methods: Fukuoka City is the fifth most populous ordinance-designated city in Japan, with an estimated population of approximately 1.6 million. Under an agreement with Fukuoka City, Kyushu University was granted access to a portion of the city's anonymized healthcare database as secondary-use information. The database contains information on resident registration, health insurance claims, specific health checkups and health checkups for the older adults, specific health guidance, long-term care insurance data, and cancer screenings collected after fiscal year 2012. Each of these constituent datasets can be interlinked using anonymized hashed key variables, allowing individuals to be followed across databases and over time., Conclusions: The platform allows longitudinal investigation of the complex association between various aspects of healthcare, such as medical procedures, examinations, interviews, medical costs, long-term care certifications, and care costs. The platform can provide valuable public-health information because it is relatively large for a single database, and because it allows analysis of data across multiple domains and tracing of individuals over time., Competing Interests: TN received a commissioned research fund for the Fukuoka City health promotion policy. TN is a member of the Fukuoka 100 Project Promotion Council of Fukuoka City. DY is a member of the Liaison Conference on Specific Health Checkups and Specific Health Guidance. The other authors have no competing interests to declare., (© 2024 Society for Clinical Epidemiology.)

Background: It has been found that brain atrophy develops more rapidly in patients with end-stage renal failure after initiation of dialysis therapy. The present study was designed to analyze the relationship between brain atrophy and asymptomatic ischemic brain lesions., Patients and Methods: Magnetic resonance imaging (MRI) was performed for the evaluation of brain atrophy and ischemic lesions. Brain atrophy was assessed by the ventricular-brain ratio (VBR), calculated as the ratio of the ventricular area to the whole brain area on the maximum MRI slice. The severity of periventricular hyperintensity (PVH) and the number of lacunae were also regarded as ischemic brain lesions. Fifty-five patients undergoing maintenance hemodialysis (HD) without clinically overt neurological signs and symptoms, with a mean age of 52 +/- 11 (SD) years and a mean HD duration of 7 +/- 6 (SD) years were subjected. VBR and its relationship to ischemic brain lesion data were compared to those in 35 non-HD patients (controls), with a mean age of 42 +/- 14 (SD) years., Results: The VBR, the number of lacunae and the severity of PVH tended to increase with age in HD. The VBRs at all age groups were significantly higher in HD than in controls (7.0 vs 3.7% at the 4th decade, p < 0.05; 8.4 vs 5. 9% at the 5th decade, p < 0.05; 9.6 vs 5.4% at the 6th decade, p < 0.05; and 11.6 vs 6.3% at the 7th decade, p < 0.05). HD patients had significantly higher number of lacunae and had more advanced PVH than did controls. Both the number of lacunae and the severity of PVH were significantly correlated to VBR in HD., Conclusion: In conclusion, the rapid progression of brain atrophy was related to the asymptomatic ischemic brain lesions in our HD patients. Such data indicated that cerebral ischemia might be a causative mechanism of brain atrophy in chronic hemodialysis patients.

The renal hemodynamic response to pressor substances in the diseased kidney has been suggested to be different from that in the normal kidney. The aim of this study was to investigate the effects of endothelin and angiotensin II on renal hemodynamics in experimental nephritis induced by the administration of antithymocyte serum in Wistar rats. This model showed mesangiolytic lesions in the glomeruli on day 2 and hypercellular lesions on day 8. Prior to the injection of either endothelin or angiotensin II, the glomerular filtration rate and renal plasma flow were significantly lower in model rats on day 2 or day 8 than in the control rats. The basal glomerular filtration rate and renal plasma flow on day 8 were negatively correlated with the mesangium cell number. The injection of endothelin (0.5 ng/kg BW) led to a decrease in both renal plasma flow and glomerular filtration rate in rats on day 8 which was significantly greater than that in the control rats. Similarly, angiotensin II infusion (0.2 micrograms/kg BW) reduced both renal plasma flow and glomerular filtration rate in the rats on day 8 and the reductions were significantly greater than those in the control rats. In conclusion, renal hemodynamics in rats with mesangial proliferation of the kidney were more sensitive to both endothelin and angiotensin II than those in the normal kidney.

TGF-beta plays a pivotal role in the pathological accumulation of extracellular matrix in experimental glomerulonephritis. Increased TGF-beta expression leads to increased synthesis and deposition of extracellular matrix components while administration of anti-serum to TGF-beta suppresses the major manifestations of the disease. We hypothesized that TGF-beta might also enhance matrix accumulation by decreasing matrix turnover via effects on protease/protease inhibitor balance. Plasmin is a potent protease capable of degrading a variety of matrix molecules. Plasmin generation from plasminogen is regulated by plasminogen activator(s) (PA) and plasminogen activator inhibitor(s) (PAI). In this study PA activity was markedly reduced and PAI-1 synthesis dramatically increased when TGF-beta was added to normal glomeruli. Diseased glomeruli also showed decreased PA activity, increased PAI-1 synthesis and increased PAI-1 deposition into matrix. Administration of anti-TGF-beta serum to glomerulonephritic rats blocked the expected increase in glomerular PAI-1 deposition. Thus changes in the PA/PAI balance favoring accumulation of matrix are induced by TGF-beta in normal glomeruli and are present in nephritic glomeruli when endogenous TGF-beta production is high. Our findings implicate the plasmin protease system in tissue repair following acute glomerular injury and suggest another mechanism by which TGF-beta enhances the matrix accumulation characteristic of many glomerular diseases.

Using lectin (PNA) and monoclonal antibodies for Pgp-1, IL-2R, H-2k, CD3, and F23.1 (T cell receptor V beta 8), we characterized the 'radioresistant' CD4-CD8- double negative thymocytes at an early stage after 800 rad irradiation. Most of the CD4-CD8- cells on day 8 after irradiation expressed a high level of Thy-1, H-2k, and PNA, while a small proportion of these cells were CD3+ and/or F23.1+. The appearance of Pgp-1 and IL-2R on the 'radioresistant' double negative precursors was also sequentially examined from day 5 to day 9 after irradiation. The double negative thymocytes at day 5 expressed the highest level of Pgp-1 antigens and these cells gradually decreased in number from day 7 to day 9. By contrast, IL-2R was transiently expressed on the double negative cells on the day 7 and 8 after irradiation. These results indicate that progression of thymocyte development occurred within the CD4-CD8- thymocytes after irradiation. We further examined the homing ability of the double negative 'radioresistant' intrathymic T cell precursors to the periphery by intrathymic cell transplantation method. The double negative thymocytes proliferate and differentiate into CD4+CD8+ cells and CD4+CD8- cells but few CD4-CD8+ cells in the thymus, while only CD4-CD8+ cells were detected in the peripheral lymphoid organs 14 days after intrathymic transplantation of the double negative cells in the H-2 compatible Thy-1 congenic mice. These results suggest that the 'radioresistant' intrathymic precursors differentiate and mature in the thymus and migrate to the periphery.

The incidences of cerebral hemorrhage (CH), cerebral infarction (CI) and subarachnoid hemorrhage (SAH) were examined retrospectively in patients with chronic renal failure on maintenance hemodialysis, followed for 13 years in our 26 satellite dialysis centers. During 10,364 patient-years of experience (PYE), CH developed in 66, CI in 16, SAH in 3 and unclassified stroke in 5 cases. The incidence was 637 per 10(5) PYE for CH and 154 for CI, the former being approximately 5 times and the latter one third of the incidence of CH or CI in the general population in Japan. Forty-six percent of fatal CH cases died within 24 hours and 73% within 3 days after the onset, while 13% of CI deaths died within 24 hours and 26% within 3 days. These data suggest that factors such as the regular use of heparin as an anticoagulant in hemodialysis patients or other inherent factors in these patients may increase vulnerability to CH and decrease the probability of CI.

The plasma concentration and urinary excretion of a newly developed angiotensin I converting enzyme inhibitor, alacepril (which is converted to captopril after absorption), were investigated in seven normal healthy subjects. Fifty milligrams of the drug was administered orally either in the fasting or in the fed state. In the fasting state, the time of maximal plasma concentration (tmax) was 1 hour for free captopril, 1.7 hours for protein-conjugated captopril, and 1.6 hours for total captopril. The biologic t1/2 of free, protein-conjugated, and total captopril was 1.9, 4.2, and 5 hours, respectively. In the fed state, neither tmax nor t1/2 changed, except that the tmax of free captopril was prolonged to 1.9 hours (P less than 0.01). Cumulative urinary excretion of free captopril at 8 hours was 35% of the drug administered in the fasting state and that of total captopril at 24 hours was 59%. These data did not differ significantly from those obtained after food intake. The biologic t1/2 of free captopril after alacepril dosing was longer than in previous studies of captopril per se. Because biologic or clinical effects have not been studied, it should be left conjectural whether alacepril is a longer-acting angiotensin I converting enzyme inhibitor. A prolonged effect of the drug can be expected by its administration after a meal.

We have studied the expression and sequences of T cell receptor gamma and delta chain gene messages in intrathymic T cell precursors of mice irradiated with 600 rads. On day 7 after irradiation a high level of expression of gamma and delta chain messages was detected in thymocytes which were composed of a relatively high proportion of CD3+CD4-CD8- thymocytes. During further development of the precursors from day 7 to day 14 after irradiation, gamma and delta chain messages fell to low levels and alpha and beta mRNA levels increased. Nucleotide sequence analysis of 14 gamma and 10 delta chain complementary DNA (cDNA) in the thymocytes on day 7 revealed that there were 7 functional gamma chain transcripts composed of V gamma 2-J gamma 2-C gamma 2 or V gamma 1-J gamma 4-C gamma 4 gene segments, and only 1 functional delta chain transcript composed of the V delta M23-D delta 1-D delta 2-J delta 1-C delta gene segments. The repertoire of gamma chain and delta chain genes used in "radioresistant" intrathymic T cell precursors of adult mice appears to be limited.