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This 5-year longitudinal study investigated the relationship between depressive symptoms and fracture risk in a large Japanese cohort. Depressive symptoms were a significant risk factor for hip fractures in women., Purpose: A relationship between depressive symptoms and fractures has not been clearly demonstrated. We aimed to investigate the relationship between depressive symptoms and 5-year fracture risk in the Japan Public Health Center-based Prospective Study for the Next Generation., Methods: From 2011 to 2016, 114,092 participants were enrolled, and a follow-up survey was conducted 5 years later. We analyzed 30,552 men and 38,063 women aged 40-74 years who had no past fractures at baseline. Presence of depressive symptoms was defined as a modified 11-item Center for Epidemiological Studies Depression Scale score of 8 or higher, a history of depression, or use of antidepressants. Subjects were asked to report vertebral, upper limb, and/or hip fractures, except for traffic or work accidents, that occurred during the follow-up period. The adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for fracture were analyzed via logistic regression analysis to evaluate the relationship between depressive symptoms and fracture., Results: Women with depressive symptoms demonstrated a high AOR for hip fractures (AOR: 2.78, 95% CI: 1.30 - 5.92); this result was consistent in post menopause women. In men, this association was not found for any age group or any type of fracture., Conclusions: Depressive symptoms in women may increase the risk of hip fractures. Further studies are required to explore this relationship in more detail., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background & Aims: Evidence on the impact of beverage consumption on depression is limited in the Asian population. Specifically, there is little information available on vegetable and fruit juices, while whole vegetables and fruits are reportedly protective against depression. Furthermore, evidence is scarce in differentiating the impacts of sweetened and black coffee. We aimed to examine the association of the consumption of total sugary drinks, carbonated beverages, vegetable and fruit juices, sweetened and black coffee, and green tea with subsequent depression in a general population sample., Methods: We studied individuals without a history of cancer, myocardial infarction, stroke, diabetes, or depression at baseline in 2011-2016, with a five-year follow-up. We used Poisson regression models and the g-formula, thereby calculating the risk difference (RD) for depression. Multiple sensitivity analyses were conducted. Missing data were handled using random forest imputation. We also examined effect heterogeneity based on sex, age, and body mass index by analyzing the relative excess risk due to interaction and the ratio of risk ratios., Results: In total, 94,873 individuals were evaluated, and 80,497 completed the five-year follow-up survey for depression. Of these, 18,172 showed depression. When comparing the high consumption group with the no consumption group, the fully adjusted RD (95% CI) was 3.6% (2.8% to 4.3%) for total sugary drinks, 3.5% (2.1% to 4.7%) for carbonated beverages, 2.3% (1.3% to 3.4%) for vegetable juice, 2.4% (1.1% to 3.6%) for 100% fruit juice, and 2.6% (1.9% to 3.5%) for sweetened coffee. In contrast, the fully adjusted RD (95% CI) was -1.7% (-2.6% to -0.7%) for black coffee. The fully adjusted RD for green tea did not reach statistical significance. The results were robust in multiple sensitivity analyses. We did not find substantial effect heterogeneity based on sex, age, and body mass index., Conclusions: Total sugary drinks, carbonated beverages, vegetable and fruit juices, and sweetened coffee may increase the risk of depression, whereas black coffee may decrease it., Competing Interests: Conflict of interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Whether the association between metabolic syndrome (MetS) and functional disability differs depending on sex or age remains unknown. To determine the association between MetS and functional disability in older people separately by sex and age groups. A total of 11 083 participants (4407 men and 6676 women) aged 65 years or over without functional disability were enrolled. MetS was defined according to the revised NCEP ATP III guidelines. Functional disability was defined by a new certification in the long-term care insurance in Japan. Cox proportional hazards models were used to assess the risk of functional disability with adjustment for possible confounding factors. Over the mean observation period of 10.5 years, 1282 men and 2162 women experienced functional disability. For those aged 65 to 74 years, HRs (95% CIs) for functional disability in the MetS group were 1.33 (1.07-1.66) in men and 1.15 (1.000-1.32) in women. For those aged 75 years or older, there was no significant association in men or women. In subjects with a severe care need level, there was a marginal significant association in men aged 65 to 74 years. Among the MetS components that independently increased the risk of functional disability were glucose intolerance and elevated blood pressure (men and women aged 65-74 years), obesity (women aged 65-74 years), and glucose intolerance (women aged 75 years or older). MetS contributed to an increase in a high risk of future functional disability among individuals aged 65 to 74 years. In this age group, improvement of lifestyle, health promotion and interventions for MetS from middle age may prevent future functional disability., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.T-U., K.T., Y.Y., and A.O received a research grant from Eli Lilly Japan K.K. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. None of the other authors declares a conflict of interest.

Aim: To fill the knowledge gap regarding weight change and the onset of disability in community-dwelling Japanese older adults, we investigated the potential effects of rapid weight change on disability risk as defined by Japan's long-term care insurance (LTCI) system., Methods: We analyzed data from a longitudinal study of 10 375 community-dwelling older Japanese adults (≥65 years) who were not LTCI needs certified at baseline and joined the study from 2002 to 2005. Weight change (percentage) was calculated by subtracting participants' weight in the previous year from that measured during a physical examination at study commencement. The five weight-change categories ranged from sizable weight loss (≤ -8.0%) to sizable weight gain (≥ +8.0%). Disability was defined according to LTCI certifications at follow-up. Hazard ratios (HRs) and 95% confidence intervals were calculated for new-onset disability using a Cox proportional hazards model that fitted the proportional subdistribution hazards regression model with weights for competing risks of death., Results: During the mean 10.5-year follow-up, 2994 participants developed a disability. Sizable weight loss (HR [95% confidence intervals], 1.41 [1.17-1.71]) and weight loss (1.20 [1.05-1.36]) were significant predictors of disability onset. Sizable weight gain (1.45 [1.07-1.97]) corresponded to severe disability. Stratified analyses by lifestyle and initial body mass index categories revealed more pronounced associations between weight change and disability risk in the unhealthy lifestyle and below initial normal body mass index groups., Conclusions: Rapid and sizable weight gain could be additional criteria for disability risk in older adults. Geriatr Gerontol Int 2023; 23: 809-816., (© 2023 Japan Geriatrics Society.)

Glomus tumours are painful superficial tumours, and ultrasonography is an extremely useful and noninvasive diagnostic technique for superficial organs. In this study, we retrospectively examined glomus tumours using ultrasonography. Among 18 patients histopathologically diagnosed with glomus tumours via ultrasonography, we observed five different development sites: subungual areas or those surrounding the nail bed (12), other areas on the finger surface (3), abdominal wall (1), upper arm (1), and forearm (1). The ultrasonographic images revealed significant differences in tumour size, indicating that tumours on other body surfaces tended to be smaller than those on patients' fingers ( p  < 0.01). The depth/width ratios of tumours on the other body surfaces were significantly higher than those on the fingers ( p  < 0.05). The tumours showed a regular shape (72.2%) and clear border (100%). Furthermore, most tumours were low-echo tumours with a diameter of up to 15 mm, clear margins, and no lateral shadows. Abundant blood flow and vessels in and out of the tumours were also observed. In conclusion, our study describes the ultrasonographic characteristics of glomus tumours and reveals that they cannot be ruled out when diagnosing small painful subcutaneous tumours., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2023 Noboru Takanashi et al.)

Purpose: To determine the effect of the formulation of topical medications on the healing of corneal epithelial cells after phototherapeutic keratectomy (PTK)., Study Design: Retrospective cohort study., Methods: We studied 271 eyes of 189 consecutive patients (aged 67.6 ± 11.8 years) who had undergone PTK for granular corneal dystrophy (n = 140), band keratopathy (n = 47), or lattice corneal dystrophy (n = 2). Postoperatively, generic or brand-named levofloxacin, 0.1% betamethasone, or 0.1% bromfenac sodium hydrate was applied topically. Patients were examined on postoperative days 1, 2, and 5 and weekly thereafter. The time to re-epithelialization was assessed by use of Kaplan-Meier and Cox proportional hazards analyses., Results: The time to re-epithelialization was significantly longer with generic 0.5% levofloxacin, at 8.2 ± 3.5 days, than with 0.5% Cravit (levofloxacin), at 6.7 ± 3.5 days (P = 0.018), or with 1.5% Cravit, at 6.3 ± 2.6 days (P = 0.000). In addition, the time to re-epithelialization was significantly longer with generic 0.1% betamethasone (Sanbetason), at 7.3 ± 3.4 days, than with brand-name 0.1% betamethasone (Rinderon), at 6.1 ± 2.5 days (P = 0.0002). The Cox proportional hazards model indicated that the use of generic formulations for levofloxacin eye drops and 0.1% betamethasone was a significant factor that delayed corneal re-epithelialization (hazard ratio [HR] = 0.72, P = 0.002 and HR = 0.77, P = 0.006, after adjustment for age). Re-epithelialization was significantly shorter in band keratopathy than in corneal dystrophy (HR = 1.56, P = 0.004). No other factors, including age, bandage contact lens, and diabetes mellitus, were significantly associated with time to re-epithelialization., Conclusion: Corneal epithelial healing can be significantly affected by different antibacterial or steroid eye drops. Clinicians need to be aware that a generic formulation may affect corneal epithelial healing., (© 2023. Japanese Ophthalmological Society.)

People who experience natural disasters have a high risk of developing cardiovascular diseases. We investigated the association between the extent of house collapse and urine sodium-to-potassium (UNa/K) ratio of 2011 Great East Japan Earthquake victims. We used the baseline survey data of the Tohoku Medical Megabank Project Community-Based Cohort Study of 29 542 individuals (aged 20-74 years) residing in the affected areas. The UNa/K ratio was calculated using spot urinary electrolyte values. Analysis of covariance was used to calculate the multivariate-adjusted geometric means of the UNa/K ratio in the following groups stratified according to the self-reported extent of house collapse: total collapse (TC), half collapse (HC), partial collapse (PC), and no damage (ND). Multivariable-adjusted odds ratios (ORs) for a high UNa/K ratio were calculated using logistic regression. The TC, HC, PC, and ND groups comprised 5 359 (18.1%), 3 576 (12.1%), 7 331 (24.8%), and 13 276 (44.9%) participants, respectively. The TC (3.33; 95% confidence interval [CI], 3.28-3.38), HC (3.37; 3.30-3.43), and PC (3.32; 3.28-3.37) groups had significantly higher multivariate-adjusted geometric means of the UNa/K ratio than the ND (3.24; 3.21-3.27) group. The multivariable-adjusted ORs (95% CIs) for a high UNa/K ratio in the TC, HC, and PC groups vs. the ND group were 1.07 (0.99-1.15), 1.20 (1.11-1.31), and 1.20 (1.12-1.28), respectively. Similar associations between house collapse and UNa/K ratio were observed for both sexes. We report that victims of a natural disaster tend to have a diet with high sodium-to-potassium ratio., (© 2023. The Author(s).)

Background: Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) are enzymes associated with diabetes mellitus (DM) prevalence. However, limited information is available regarding the association of liver enzymes and DM consistently present in obese and non-obese individuals. We examined whether the combination of ALT and GGT enzymes is associated with the prevalence of DM, regardless of obesity, in a general Japanese population., Methods: We conducted a cross-sectional study of 62,786 participants aged ≥20 years who lived in Miyagi and Iwate, Japan. We divided all the participants into eight groups according to the ALT level (low: <30 IU/L and high: ≥30 IU/L), GGT level (low: <50 IU/L and high: ≥50 IU/L), and the presence of obesity. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression analysis, adjusting for potential confounders, to determine associations of the combination of ALT and GGT levels and obesity with DM prevalence., Results: Overall, 6,008 participants (9.6%) had DM. Compared to non-obese individuals with low ALT and GGT levels, the participants with high ALT and GGT levels had high ORs for DM in both obese (OR 4.06; 95% CI, 3.61-4.56) and non-obese groups (OR 2.19; 95% CI, 1.89-2.52). The obese group had high ORs for DM, even at low ALT and GGT levels., Conclusion: High ALT and GGT levels are associated with DM prevalence in obese and non-obese participants. This finding suggests that correcting ALT and GGT levels and controlling obesity are important for the prevention of DM.

This study aimed to investigate whether social isolation is associated with mortality, together with the effect of the Great East Japan Earthquake on mortality, due to the social isolation of community residents living in the affected areas, using data from the Tohoku Medical Megabank Project Community-Based Cohort Study. A total of 22,933 participants (8059 men and 14,874 women), who were free from cancer and cardiovascular disease, were followed up with death as an endpoint for five years. Social isolation was assessed using the Lubben Social Network Scale (cut-off, 11/12). Using Cox proportional hazards models, hazard ratios (HRs) of total mortality and 95% confidence intervals (CIs) associated with social isolation (no isolation as the reference) were estimated. The latter was significantly associated with an increased risk of total mortality (1.38 (1.04-1.83) in men and 1.49 (1.02-2.19) in women). Moreover, among those with social isolation, the risk of mortality was significantly higher, especially for women with house damage and men who had experienced a death in the family. The disaster may have raised the risk of mortality due to social isolation.

This study aimed to review evidence on future long-term care associated with pre-existing factors among community-dwelling Japanese older adults. We systematically searched cohort and nested case-control studies published between 2000 and 2019 that assessed long-term care certification using the PubMed, CINAHL, and EMBASE databases. The relationship between long-term care insurance information and risk factors was investigated. The protocol was registered with the Open Science Framework. We extracted 91 studies for synthesis, including 84 prospective cohort studies, 1 retrospective cohort study, and 6 nested case-control studies. Certification for long-term care was classified into two endpoints: onset of functional disability and dementia. There were 72 studies that used long-term care certification as a proxy for functional disability, and 22 used long-term care information to indicate the onset of dementia. Common risk factors related to functional disability were physical function, frailty, and oral condition. Motor function and nutritional status were common risk factors for dementia. We found consistent associations between premorbid risk factors and functional disability and dementia. The accumulation of evidence on the incidence of long-term care and associated factors can aid the development of preventive measures. Future studies should aim to integrate this evidence.

We aimed to evaluate the association between the milk consumption and incident stroke in a Japanese population, where milk consumption is lower than that of Western countries. In total, 14,121 participants (4253 men and 9868 women) aged 40-69 years, free from cardiovascular diseases (CVD) were prospectively followed for 10.7 years. Participants were categorized into four groups according to the milk intake frequency obtained from a brief-type self-administered diet questionnaire. The adjusted HRs of total stroke, ischemic stroke and haemorrhagic stroke associated with milk intake frequency were calculated using the Cox proportional hazards model. During the follow-up, 478 stroke cases were detected (208 men and 270 women). Compared to women with a milk intake of <2 cups/week, those with an intake of 7 to <12 cups/week had a significantly low risk of ischemic stroke in a model adjusting CVD risk factors; the HR (95% CI) was 0.53 (0.32-0.88). No significant associations were found in men. This study suggested that milk intake of 7 to <12 cups/week decreased the risk of ischemic stroke in Japanese women. Milk intake of about 1 to <2 cups/day may be effective in the primary prevention of ischemic stroke in a population with low milk intake.

Background: Social isolation and mental health issues have become a severe problem in disaster areas in the Great East Japan Earthquake. This study examined whether the combination of the house damage and social isolation or the combination of the death of family members and social isolation is associated with depressive symptoms among survivors using the baseline study data of the Tohoku Medical Megabank Project Community-Based Cohort Study (TMM CommCohort Study)., Methods: We used cross-sectional data from a baseline survey of 48,958 participants (18,423 males, 30,535 females; aged 60.1 ± 11.2 years) to examine the association between social isolation measured by the Lubben social network scale 6 (LSNS-6) and depressive symptoms measured by the Center for Epidemiological Studies-Depressive Scale (CES-D). The presence of social isolation and depressive symptoms was defined by an LSNS-6 score of < 12 and a CES-D score of ≥16, respectively. We performed a logistic regression analysis to determine the multivariable-adjusted odds ratio (95% confidence interval) [AOR (95% CI)] for depressive symptoms according to sex in the social isolation in comparison to without social isolation, and the associations of the combination of the house damage or the death of family members and social isolation and depressive symptoms., Results: Social isolation was significantly associated with depressive symptoms (males: OR = 1.87; 95% CI = 1.72-2.04, females: OR = 2.13; 95% CI = 2.00-2.26). Both males and females respondents with severe house damage and social isolation had a greater risk of depressive symptoms in comparison to those with an undamaged house and without social isolation (males: OR = 3.40; 95% CI = 2.73-4.24, females: OR = 2.92; 95% CI = 2.46-3.46). The risk of depressive symptoms was also higher in both males and females respondents with the death of family members and social isolation in comparison to those without the death of family members and without social isolation (males: OR = 2.18; 95% CI = 1.90-2.50, females: OR = 2.60; 95% CI = 2.35-2.88)., Conclusion: The findings suggested that a combination of social isolation and severe house damage and the death of family members caused by a large-scale natural disaster was associated with a higher risk of depressive symptoms although the interaction was not statistically significant.

Objective　An increasing incidence of disuse syndrome is commonly observed in areas affected by large-scale natural disasters. Consequently, the fall risk is high in such populations, necessitating adequate attention to fall prevention measures. It is important to identify factors associated with falls to prevent deterioration in functional ability. We investigated the risk factors associated with falls among elderly survivors in disaster-stricken areas using longitudinal data from the Research project for the prospective Investigation of health problems Among Survivors of the Great East Japan Earthquake (RIAS) Study.Methods　Of all data obtained from the RIAS Study, we used the data of 1,380 survivors who were aged ≥65 years, were not diagnosed with cancer or cardiovascular disease, did not need supportive care, and could participate in the annual survey between 2011 and 2016. Self-administered questionnaires were distributed, and anthropometric and grip tests were performed during the 2011 survey to obtain information regarding housing damage, the fear of falls, arthralgia, cognitive function psychological distress, insomnia, frequency of leaving the house, a history of hypertension, dyslipidemia, diabetes, alcohol consumption status, smoking status, and/or body mass index, and grip strength. Based on the responses obtained from each annual survey, a fall was defined as an event during which an individual had fallen at least once. Multivariate-adjusted odds ratio(OR) and 95% confidence interval(CI) for all variables related to falls were calculated using logistic regression with adjustment for sex and residential area. Similar analyses were performed based on age groups (65-74 years and ≥75 years).Results　The 5-year fall incidence rate was 35.5% (31.9% [men], 37.9% [women]). In men, cognitive dysfunction was significantly associated with falls (OR 1.50, 95%CI 1.01-2.22). In women, cognitive dysfunction (OR 1.82, 95%CI 1.34-2.47), insomnia (OR 1.41, 95%CI 1.02-1.94), dyslipidemia (OR 1.58, 95% 95% CI 1.11-2.25), and a history of smoking (OR 4.30, 95%CI 1.08-17.14) were significantly associated with falls. In women aged ≥75 years, partial housing damage (OR 7.93, 95%CI 1.85-33.91) and psychological distress (OR 2.83, 95%CI 1.09-.7.37) were also significantly associated with falls.Conclusion　This study suggests that cognitive dysfunction in both sexes and insomnia, dyslipidemia, and a history of smoking in women were significantly associated with falls, and partial housing damage and psychological distress were risk factors for falls in women aged ≥75 years. Fall prevention after large-scale natural disasters warrants close attention to known risk factors and environmental and mental health changes.

Background: We established a community-based cohort study to assess the long-term impact of the Great East Japan Earthquake on disaster victims and gene-environment interactions on the incidence of major diseases, such as cancer and cardiovascular diseases., Methods: We asked participants to join our cohort in the health check-up settings and assessment center based settings. Inclusion criteria were aged 20 years or over and living in Miyagi or Iwate Prefecture. We obtained information on lifestyle, effect of disaster, blood, and urine information (Type 1 survey), and some detailed measurements (Type 2 survey), such as carotid echography and calcaneal ultrasound bone mineral density. All participants agreed to measure genome information and to distribute their information widely., Results: As a result, 87,865 gave their informed consent to join our study. Participation rate at health check-up site was about 70%. The participants in the Type 1 survey were more likely to have psychological distress than those in the Type 2 survey, and women were more likely to have psychological distress than men. Additionally, coastal residents were more likely to have higher degrees of psychological distress than inland residents, regardless of sex., Conclusion: This cohort comprised a large sample size and it contains information on the natural disaster, genome information, and metabolome information. This cohort also had several detailed measurements. Using this cohort enabled us to clarify the long-term effect of the disaster and also to establish personalized prevention based on genome, metabolome, and other omics information.

Phase-sensitive detection is the essential projective measurement for measurement-based continuous-variable quantum information processing. The bandwidth of conventional electrical phase-sensitive detectors is up to several gigahertz, which would limit the speed of quantum computation. It is theoretically proposed to realize terahertz-order detection bandwidth by using all-optical phase-sensitive detection with an optical parametric amplifier (OPA). However, there have been experimental obstacles to achieve large parametric gain for continuous waves, which is required for use in quantum computation. Here, we adopt a fiber-coupled χ (2) OPA made of a periodically poled LiNbO 3 waveguide with high durability for intense continuous-wave pump light. Thanks to that, we manage to detect quadrature amplitudes of broadband continuous-wave squeezed light. 3 dB of squeezing is measured up to 3 THz of sideband frequency with an optical spectrum analyzer. Furthermore, we demonstrate the phase-locking and dispersion compensation of the broadband continuous-wave squeezed light, so that the phase of the squeezed light is maintained over 1 THz. The ultra-broadband continuous-wave detection method and dispersion compensation would help to realize all-optical quantum computation with over-THz clock frequency.

Background: Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. Recently, its incidence has been increasing worldwide. We encountered a young woman who presented with induration mimicking squamous cell carcinoma in the lower lip, without major medical conditions., Case Presentation: A 25-year-old Japanese woman presented with a 1-month history of a painless induration in her lower lip. Because squamous cell carcinoma was suspected, a preoperation work up was performed, including laboratory tests, an ultrasonographic examination, and a biopsy. The ultrasonography findings showed an oval-shaped 17 × 11 × 12 mm tumor-like lesion with heterogeneous internal echo and an indistinct border. A pressure test and color Doppler sonography revealed that the lesion was soft with a very abundant blood flow. These findings suggested the possibility of underlying inflammatory causes rather than a neoplastic tumor. Serology tests for syphilis, including the anti-Treponema pallidum antibody and reactive rapid plasma reagin tests, were positive. The biopsy revealed no malignancy. Finally, she was diagnosed as having primary syphilis and treated with amoxicillin for 28 days. The rapid plasma reagin value gradually decreased and the initial induration in her lower lip disappeared., Conclusion: This case highlights the need for prompt examinations for possible underlying infective causes, such as syphilis, when seeing a painless induration with ulcer in the lip. Ultrasonography was helpful in the differential diagnosis of a tumor-like lesion and should be included in addition to syphilis serology tests, such as anti-Treponema pallidum antibody and rapid plasma reagin tests.

Purpose: We present our findings in two cases of retinal dysfunction caused by syphilitic outer retinopathy. CASE 1: A 59-year-old man visited our clinic complaining of blurred vision in his left eye. Optical coherence tomography (OCT) demonstrated an absence of the ellipsoid zone (EZ) in the left eye. A round yellowish-white lesion was observed in the posterior pole of the left fundus. Fundus autofluorescence (FAF) showed hyperfluorescent areas in the posterior pole of both fundi although no specific ophthalmoscopic findings were seen in the right eye. The amplitudes of the LA 3.0 1 Hz and LA 3.0 30 Hz ERG responses were reduced with better preservation of the rod responses. Based on a strong positivity to the rapid plasma reagin (RPR) assay and the Treponema pallidum hemagglutination (TPHA) test, he was diagnosed with syphilitic outer retinopathy and treated with systemic antibiotics. The treatment resulted in a restoration of the retinal structures and cone function. CASE 2: A 47-year-old man was referred to our clinic complaining of reduced vision in both eyes. Although the ocular fundus appeared normal, FAF showed a diffuse hyperfluorescent area in the posterior pole and multiple hyperfluorescent spots. Indocyanine green angiography showed multiple confluent areas of hypofluorescence. OCT demonstrated irregular EZs in both eyes. The amplitudes of the LA 3.0 1 Hz and LA 3.0 30 Hz ERG responses were slightly reduced with prolonged implicit times. These findings are comparable to the findings in patients with multiple evanescent white dot syndrome. However, the strong positivity to the RPR and TPHA tests led us to diagnose the patient with outer retinopathy caused by syphilis. Systemic administration of antibiotics resulted in the restoration of the retinal structures and retinal function., Conclusions: Syphilitic outer retinopathy affected the retinal structures and function that can be restored by antibiotic treatments.

We report generation and measurement of a squeezed vacuum from a semi-monolithic Fabry-Pérot optical parametric oscillator (OPO) up to 100 MHz at 1550 nm. The output coupler of the OPO is a flat surface of a nonlinear crystal with partially reflecting coating, which enables direct coupling with waveguide modules. Using the OPO, we observed 6.2dB of squeezing at 2 MHz and 3.0 dB of squeezing at 100 MHz. The OPO operates at the optimal wavelength to minimize propagation losses in silica waveguides and looks towards solving a bottleneck of downsizing these experiments: that of coupling between a squeezer and a waveguide.

We describe the optical conditions that are essentially necessary for phase-contrast imaging with aberration-corrected scanning transmission electron microscopy (STEM), whose depth of field has reached almost comparable to the specimen thickness. For such state-of-the-art STEM, contrast-transfer-function (CTF) should be defined not solely for the projected potential but multiply for each wavefront during the beam propagation across the specimen thickness; an integration of multiple CTFs (iCTF). We show that the iCTF concept explains fairly well characteristic annular-bright-field (ABF) imaging behaviors of heavy/light atom sites against the defocus changes, and also provide notable concerns on possible artifacts that arise from different imaging-depth dependences between the heavy/light atom sites., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the usefulness of sonography for monitoring the response to glucocorticoid treatment in patients with immunoglobulin G4 (IgG4)-related disease., Methods: We conducted a retrospective study using sonography in 12 patients with bilateral swollen submandibular glands who had a diagnosis of IgG4-related disease based on an elevated serum IgG4 level (>135 mg/dL) and histopathologic findings between January 2010 and December 2012. Among these patients, 6 were treated with prednisolone, and the other 6 were placed under observation. B-mode sonographic examinations of the submandibular glands were performed with or without color Doppler imaging at the initial examination and 6 months later. Findings were compared between the groups (treated and untreated), and their relationship with the treatment response of the primarily involved organs was investigated., Results: In the treated group, the submandibular glands of all 6 patients decreased in both size and volume after treatment (average volume ± SD, 27,449.7 ± 24,227.6 to 4609.7 ± 1911.4 mm(3); P = .004). The internal echo texture, characterized by multiple hypoechoic foci scattered against a heterogeneous hyperechoic background of submandibular tissue with demarcated hyperechoic lines, with or without hypoechoic tumor formation, disappeared or was obscured in all cases. In addition, the blood flow signals were reduced in all 3 patients who underwent color Doppler sonography, and the response observed on sonography was found to correlate with the IgG4 level and recovery of specific organ involvement. In contrast, in the untreated group, the submandibular glands showed a tendency to increase in both size and volume (average volume, 9326.3 ± 3054.8 to 12,217.4 ± 4605.5 mm(3); P= .2) without a decrease in the blood flow signals., Conclusions: Sonography is considered useful for evaluating the response to glucocorticoid therapy in patients with IgG4-related disease of the submandibular glands., (© 2015 by the American Institute of Ultrasound in Medicine.)

Background: Previously, a bovine intestinal epithelial cell line (BIE cells) was successfully established. This work hypothesized that BIE cells are useful in vitro model system for the study of interactions of microbial- or pathogen-associated molecular patterns (MAMPs or PAMPs) with bovine intestinal epithelial cells and for the selection of immunoregulatory lactic acid bacteria (LAB)., Results: All toll-like receptor (TLR) genes were expressed in BIE cells, being TLR4 one of the most strongly expressed. We demonstrated that heat-stable PAMPs of enterotoxigenic Escherichia coli (ETEC) significantly enhanced the production of IL-6, IL-8, IL-1α and MCP-1 in BIE cells by activating both NF-κB and MAPK pathways. We evaluated the capacity of several lactobacilli strains to modulate heat-stable ETEC PAMPs-mediated inflammatory response in BIE cells. Among these strains evaluated, Lactobacillus casei OLL2768 attenuated heat-stable ETEC PAMPs-induced pro-inflammatory response by inhibiting NF-κB and p38 signaling pathways in BIE cells. Moreover, L. casei OLL2768 negatively regulated TLR4 signaling in BIE cells by up-regulating Toll interacting protein (Tollip) and B-cell lymphoma 3-encoded protein (Bcl-3)., Conclusions: BIE cells are suitable for the selection of immunoregulatory LAB and for studying the mechanisms involved in the protective activity of immunobiotics against pathogen-induced inflammatory damage. In addition, we showed that L. casei OLL2768 functionally modulate the bovine intestinal epithelium by attenuating heat-stable ETEC PAMPs-induced inflammation. Therefore L. casei OLL2768 is a good candidate for in vivo studying the protective effect of LAB against intestinal inflammatory damage induced by ETEC infection or heat-stable ETEC PAMPs challenge in the bovine host.

Case Report: To salvage an uneruputed tooth within a dentigerous cyst, the retransplantation of the unerupted premolar involved in the dentigerous cyst was performed. In the present case a dentigerous cyst with the impacted maxillary second premolar of a 10-year-old boy was removed, because of the missing eruption after marsupialisation of the premolar 4 months earlier. Covering the crown and the one third of root, the cyst was removed from the tooth, and the premolar was retransplanted into a cavity created between the premolar and first molar in the maxilla. The tooth was fixed with resin and a twisted wire for 1 month. Two years after transplantation, the tooth responded positively to pulp vitality tests but did not move toward the occlusal line, and dental X-ray showed a lamina dura, mineralisation of the pulp cavity, no root resorption and development.

We evaluated whether a bovine intestinal epithelial (BIE) cell line could serve as a useful in vitro model system for studying antiviral immune responses in bovine intestinal epithelial cells (IECs) and for the primary screening of immunobiotic microorganisms with antiviral protective capabilities. Immunofluorescent analyses revealed that toll-like receptor 3 (TLR3) was expressed in BIE cells, and the results of real-time quantitative PCR showed that these cells respond to stimulation with poly(I:C) by up-regulating pro-inflammatory cytokines and type I interferons. In addition, we demonstrated that BIE cells are useful for the primary screening of immunobiotic lactic acid bacteria strains which are able to beneficially modulate antiviral immune responses triggered by TLR3 activation in bovine IECs. The characterization of BIE cells performed in the present study represents an important step towards the establishment of a valuable bovine in vitro system that could be used for the development of immunomodulatory feed for bovine hosts., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The first synthesis of decahydrofluorene core 4 of pyrrocidines was accomplished. The cis,trans-fused tricyclic ring system was stereoselectively constructed via Diels-Alder reaction using two Danishefsky dienes.

Fatty acid translocase (FAT)/CD36 is a multi-functional membrane protein participating in uptake of long-chain fatty acids and oxidized low density lipoprotein, playing an important role in lipid homeostasis. We reported the dual promoter structures of the mouse and human FAT/CD36 genes in relation to the tissue-specific expression and regulation by peroxisome proliferator-activated receptors (PPARs) (Sato et.al. J. Biol. Chem. 277, 15703-15711, 2002). However, these structures alone could not explain a large induction of the mRNA by a PPAR ligand in the mouse intestine. To learn more about the tissue-specific transcriptional regulation of the FAT/CD36 gene for lipid homeostasis at the whole body level, we cloned the cDNA for the induced mRNA in the mouse intestine and identified third promoter close to the first common exon of the gene. The human gene also has essentially the same gene organization. RT-PCR and Northern blot analyses showed that the three promoters are differentially used in various mouse tissues and the cultured human cells. The physiological significance of these complex promoter structures was suggested by the differential responsiveness to a peroxisome proliferator-activated receptor ligand and the differences in translational efficiencies or stabilities of the mRNA among the isoforms.

Background: Serum levels ob biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF., Methods: Subjects consisted of 59 healthy volunteers and 102 patients: 61 with CRF undergoing hemodialysis (CRF-HD), 10 with CRF under conservative therapy (CRF-CT), 21 with renal disease (RD), and 10 with muscle disease (MD). Patients with RD, CRF, and MD were evaluated to verify the absence of myocardial injury. We developed an immunoradiometric assay to measure serum cTnI using monoclonal antibodies. The lower limit of detection was 0.33 micro g/l. Serum cTnI, creatine kinase (CK), CK-MB, cardiac troponin T (first-, second-, and third-generation assay: cTnT-I, cTnT-II, and cTnT-III), and cardiac myosin light chain 1 (cMLC1) were measured., Results: cTnI was not detected in healthy volunteers or patients with CRF, RD, or MD. In patients with CRF-HD, elevated levels occurred in 4.9% (3/61) for CK, 0% (0/61) for CK-MB, 39.5% (15/38) for cTnT-I, 7.3% (3/41) for cTnT-II, 13.0% (3/23) for cTnT-III, and 77.0% (47/61) for cMLC1; and in patients with MD the levels were increased in 70% (7/10) for CK, 50% (5/10) for CK-MB, 44.4% (4/9) for cTnT-I, 20% (2/10) for cTnT-II, and 50% (5/10) for cMLC1., Conclusions: cTnI is a highly specific marker for AMI and is particularly useful for detecting AMI in patients with CRF or MD. Serum levels of biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF.

We reported previously the clinical benefit of hepatic and splenic arterial infusion chemotherapy (HSAIC) for patients with advanced pancreatic cancer alter transcatheter peripancreatic arterial embolization (TPPAE). TPPAE has two therapeutic purposes: (1) preparation for effective arterial infusion chemotherapy, and (2) transcatheter arterial embolization (TAE) against pancreas head cancer. The present paper describes the advantage of CT arteriography in performing TPPAE for advanced pancreatic cancer. CTA was useful in identifying the arterial blood supply in pancreatic cancer, especially blood vessels branched off from the supramesenteric artery (SMA). Since the anti-tumor effect of TPPAE against pancreas head cancer is dependent mainly on whether the blood supply from SMA could be shut off, it is suggested that CTA is useful to evaluate the embolization effect of TPPAE.

Screening of various natural products in a search for novel inducers of apoptosis in human leukemia cells led us to identify the strong apoptosis-inducing activity in a fraction extracted with methanol from the roots of Sophora subprostrata Chun et T. Chen. We purified the compound that induced apoptosis in human leukemia cells and identified it as sophoranone. Sophoranone inhibited cell growth and induced apoptosis in various lines of cells from human solid tumors, with 50% inhibition of growth of human stomach cancer MKN7 cells at 1.2 +/- 0.3 microM. The growth-inhibitory and apoptosis-inducing activities of sophoranone for leukemia U937 cells were very much stronger than those of other flavonoids, such as daidzein, genistein and quercetin. At the early stages of treatment of U937 cells with sophoranone, reactive oxygen species were formed, mitochondrial permeability pores were opened and cytochrome c was released from mitochondria. Cytochrome c was also released upon treatment of isolated mitochondria with sophoranone. Inhibitors of complexes III and IV, but not complexes I and II, of the mitochondrial respiratory chain prevented the release of cytochrome c from isolated mitochondria by sophoranone, as well as the induction of apoptosis in U937 cells in response to sophoranone. Our results indicate that sophoranone might be a unique apoptosis-inducing anticancer agent that targets mitochondria., (Copyright 2002 Wiley-Liss, Inc.)

Specific direct radioimmunoassay of angiotensin II (AT II) in human plasma was developed to evaluate the dynamics of endogenous AT II in various types of hypertension. Detection limit of this method was less than 2.3 pg/ml, and normal value is less than 25 pg/ml. Cross reactivity of antibody with AT I and III was 0.037% and 21%, respectively. There were good correlation between the value measured by direct method, and that of extraction method (r = 0.96, P < 0.01) and plasma renin activity (r = 0.80, P < 0.01). By oral administration of ACE inhibitor (captopril 50 mg), AT II levels were suppressed to 10 pg/ml or less in most patients with essential hypertension, renal parenchymal hypertension and renovascular hypertension up to 2 h. However, AT II levels in patients treated with ACE inhibitors chronically were not different from the AT II levels in patients without ACE inhibitor. In primary aldosteronism AT II was extremely low levels. AT II markedly increased by the stimulation test using furosemide (1 mg/kg i.v.). These results suggest that this method may be useful to clarify the pathophysiology of hypertension and the escape of the inhibition by ACE inhibitor.

Pituitary dysfunction occasionally results from brain tumors or the surgical resection of brain tumors. The authors examined two patients with hypogonadotropic secondary amenorrhea, who had undergone surgical removal of brain tumors. Changes in immunoreactive gonadotropin-releasing hormone (GnRH) secretion are of interest in patients with a gonadotropin and gonadal steroid deficit, because both steroid and pituitary feedback systems are altered by tumors or tumor resection. The authors thus measured GnRH, luteinizing hormone, and follicle-stimulating hormone levels every 15 minutes for 4 hours by radioimmunoassay and investigated qualitative and quantitative changes in the pulsatile patterns of these hormones in two hypogonadotropic hypogonadism patients. They also performed similar multiple measurements of GnRH in two normal cycle women in follicular phase and two postmenopausal women. The concentration of plasma GnRH in two hypopituitarism patients was compared with that in two normal cycle women and two postmenopausal women. The study showed that the peripheral blood level of GnRH was significantly lower in two hypopituitarism patients than in both normal cycle and postmenopausal women, and that the pulsatile frequency was not different among these three groups. These findings suggest that alteration of feedback systems results in a decrease in the blood level of GnRH, and that pulses of GnRH maintain normal fluctuation despite the alteration of the hormonal circumstances in two hypogonadotropic hypogonadism patients.

Less than 20% of all cases of non-small cell lung cancer are operable. The treatment option available for such patients is either radiotherapy or chemotherapy. Various combinations of chemotherapeutic agents have been tried. The combination of cisplatin and 5-fluorouracil (5-FU) has been proved to have a synergistic antitumour effect in many experimental and clinical studies. In this paper the authors report the results of a trial using tegafur (which is a prodrug of 5-FU; 1-[2-tetrahydrofuryl]-5-FU) and uracil along with cisplatin in inoperable non-small cell lung cancer. Thirty-one patients were entered into the study, all of whom were less than 75 years old (mean age 61 years). The patients (except for 2) had either stage IIIB (12) or stage IV (17) disease with adenocarcinoma and squamous cell carcinoma in equal proportions (15 each). A combination of uracil and tegafur (400 mg/m2) in 100 mg capsules (100 mg tegafur and 224 mg of uracil), was given orally for 21 days. Most of the patients received 300 mg of the combination tablets twice a day. Cisplatin (80 mg/m2) was given as an infusion over 90 minutes on day 8 after adequately hydrating the patients. This cycle was repeated every 4 weeks. At least 2 treatment cycles were given, unless there was disease progression or toxicity. The response and survival rates were assessed after a follow up period which ranged between 9 and 30 months. The patients received 1 to 4 cycles of therapy and the response rates were: complete response--nil,partial response--11, no change--11 and disease progression--9. The overall response rate was 35% (95% CI: range 19-52%). Five patients achieved at least 50% tumour reduction after 2 cycles. Of the 11 patients who showed partial response, 5 (35%) had stage IV disease and 6 (36%) had other stages; 6 (40%) had squamous cell carcinomas and 5 (31%) had tumours of other histological types. The median duration of response was 6 months (3-13 months). In stage III disease, the 1-year survival rate was 31%, with a median survival time of 11 months, while in stage IV disease it was 29% with a median survival time of 8 months. There was a low incidence of toxicity, with anaemia (10%), leukopenia (6%) and thrombocytopenia (6%) being the most common side-effects. There were also no treatment-related deaths. The authors concluded that oral uracil and tegafur were as effective as other combinations with cisplatin. They also caused very few side-effects. They suggest that a larger trial needs to be carried out.

We developed a radioimmunoassay for AChR Ab using AChR solubilized from membrane extracts of human rhabdomyosarcoma cell line (RD cell). The binding affinity of this AChR to the alpha-Bungarotoxin (alpha-BTX) was similar to that of AChR from cell surface. Lyophilized AChR was stable within two months at -20 degrees C. In our assay system, sera from patients with Myasthenia Gravis (MG) showed markedly high titers and frequency (94%) of anti-AChR Ab. On the other hand, almost all sera from normal and non-myasthenic patients such as rheumatoid arthritis and thyroid disease were negative (< 0.2nmol/l). Our assay using AChR from RD cells shows sufficient results in the intra- and inter-CV values, and recovery and dilution tests. AChR Ab titers of our assay showed good correlations with those measured by AChRs from both human ischemic muscles and TE671 cells (commercial kit). The radioimmunoassay for AChR Ab using the membrane extracts of RD cells has high sensitivity, specificity and stability. Therefore, the assay is valuable as the routine assay for the diagnosis of MG.

To examine the efficacy of bleomycin on the local control of malignant pericardial effusion, we prospectively conducted a clinical trial consisting of continuous pericardial drainage and a local instillation of bleomycin. In the current study, we treated 7 patients, who suffered from malignant pericardial effusion with cardiac tamponade due to advanced-stage non-small cell carcinoma of the lung. The pericardial effusions were continuously drained through an echo-guided inserted catheter. After the effusions were drained as completely as possible, 5 mg of bleomycin were instilled locally via the catheter. In all patients but one, the draining catheter could be successfully removed. The duration of drainage ranged from 4 to 13 days (mean: 9.2 days). Five of the 7 patients achieved a complete remission of pericardial effusions, which was maintained until death or the last day of follow-up. Intrapericardial bleomycin treatment was thus found to be effective on malignant pericardial effusions without any adverse effects. However, a further study comparing the effect of pericardial instillation of bleomycin versus drainage alone would be needed for the determination of the usefulness of bleomycin.

The postrecurrent survival of 215 patients who had undergone a complete resection of non-small-cell lung cancer was examined on the basis of various factors, which included gender (female, male), age (< 65, > or = 65), the pathologic stage of disease at the time of operation (I, II, III), histologic type (squamous cell, nonsquamous cell carcinoma), type of operation (pneumonectomy, other), the selection of adjuvant treatment before recurrence (no treatment, mild chemotherapy, intensive chemotherapy and/or radiotherapy), recurrent site (local, distant), and the disease-free interval (< or = 365, > or = 365 days). A univariate analysis of the postrecurrent survival showed that the significant factors influencing the survival consisted of gender, pathologic stage, recurrent site, selection of adjuvant treatment, and the disease-free interval. Namely, female patients or patients who had pathologic stage I disease, local recurrence, no adjuvant treatment, or a disease-free interval of more than 365 days would be expected to have a prolonged survival after recurrence. Of the five significant factors, only two factors (gender and the selection of the adjuvant treatment) were found to be predominant postrecurrent prognostic factors by multivariate analysis. These observations suggest that the biologic behavior of a recurrent tumor may therefore be influenced by gender and adjuvant treatment before recurrence.

A combination chemotherapy of cisplatin and UFT was administered to fourteen patients with unresectable non-small cell lung cancer. To determine the maximum safety dose of UFT combined with CDDP (80 mg/m2), patients were assigned to three groups as follows: step 1: UFT (400 mg/m2) from day 1 to day 14; step 2: from day 1 to day 21; step 3: from day 1 to day 28. Cisplatin was administered on day 8 in each group. Myelosuppression with grade 3-4 and gastrointestinal toxicity of grade 3 were observed in one and two patients, respectively. The other toxicity was mild. There was no difference in the degree of toxicity among the three groups. The response rate of twelve evaluable patients was 50%; CR 0, PR 6, NC 4 and PD 2. Thus, chemotherapy using cisplatin 80 mg/m2 with daily administration of UFT 400 mg/m2 was considered to be well tolerated and effective in the treatment of non-small cell lung cancer.

Background: Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells and is implicated in the vascular response to injury and the pathogenesis of atherosclerosis. It is also a potent vasoconstrictor., Methods: To examine whether acute myocardial ischemia increases the level of PDGF in the coronary circulation, we measured plasma levels of PDGF in the coronary sinus and the aortic root simultaneously in 14 patients with coronary spastic angina. These measurements were performed before and after the left coronary artery spasm induced by intracoronary injection of acetylcholine, and measurements were also taken in 15 patients with stable exertional angina before and after acute myocardial ischemia induced by rapid atrial pacing. Eleven patients with chest pain but normal coronary arteries and no coronary spasm served as controls., Results: Plasma PDGF levels increased significantly (P < 0.01) from 274 +/- 28 pg/mL to 364 +/- 27 pg/mL only in coronary sinus after anginal attacks in the patients with coronary spastic angina. However, plasma PDGF levels in coronary sinus remained unchanged after these attacks in the patients with stable exertional angina (from 230 +/- 27 pg/ml to 247 +/- 28 pg/mL) and after intracoronary injection of acetylcholine in the control subjects. Plasma PDGF levels in aortic root remained unchanged in all three patient groups., Conclusions: PDGF is released into the coronary circulation after coronary artery spasm, and this may exacerbate coronary artery spasm.

To examine whether plasma platelet-derived growth factor (PDGF) levels are elevated in the coronary circulation of patients with unstable angina, the plasma PDGF levels in the coronary sinus and aortic root were simultaneously examined in 14 patients with unstable angina, 15 with stable exertional angina, and 15 control subjects. The mean plasma PDGF level (pg/ml) in the coronary sinus was significantly higher (p less than 0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (502.1 +/- 98.7 vs 301.3 +/- 62.5, and 312.7 +/- 62.6). However, there were no significant differences in mean plasma PDGF levels in the aortic root among the 3 groups. It is concluded that PDGF release is increased in the coronary circulation in patients with unstable angina.

Production of chromogranin (Cg)A and B derived peptides [pancreastatin (PST), GAWK, CCB] was studied using human lung carcinoma derived cell lines. PST-like immunoreactivity (LI) was detected in the culture medium in 3 of 6 small cell lung carcinoma (SCLC) cell lines, while GAWK- and CCB-LIs were detected in 5 of 6 and all the 6 SCLC cell lines, respectively. CCB-LI was produced in large amounts in SCLC cell lines as compared to PST- and GAWK-LIs. In non-SCLC cell lines, on the other hand, PST- and GAWK-LIs were not detected. CCB-LI was detected in 1 of 7 non-SCLC cell lines, but not detected in the remainder. PST, GAWK and CCB-LIs, secreted by these cell lines, consisted of several peaks, and these peaks were different among cell lines. This suggests that processing of CgA and B is different in the cell lines. Production of CgA and B derived peptides seems to be a characteristic feature of SCLC, and among them, CCB LI may be a useful marker for SCLC.

Inhibin levels were measured by a double antibody heterologous radioimmunoassay in the peripheral serum of 75 pregnant women throughout gestation and in serum from the umbilical vein and artery, which was obtained at the time of delivery. For reference, samples were obtained from 20 nonpregnant women in the early (days 0 to 3), mid (days 4 to 8), and late (days 9 to 14) luteal or follicular phase. Maternal serum levels of inhibin (mean +/- SEM) in early (6 to 12 weeks) gestation (36.4 +/- 2.6 U/ml, n = 36) were significantly (p less than 0.01) higher than those in serum from nonpregnant women in the mid (23.9 +/- 2.5 U/ml, n = 19) or late (11.3 +/- 0.6 U/ml, n = 19) luteal phase. Inhibin levels in maternal serum fell to 15.9 +/- 1.4 U/ml (n = 24) in mid (14 to 20 weeks) gestation and then gradually increased during late (21 to 40 weeks) gestation to peak levels of 49.4 +/- 5.1 U/ml (n = 9) at 36 to 37 weeks. Inhibin levels declined in parallel with human chorionic gonadotropin concentrations during the first trimester (r = 0.587 at p less than 0.01). Significant positive correlations (p less than 0.001) were observed between serum levels of inhibin and 17 beta-estradiol (r = 0.560), progesterone (r = 0.648), and human placental lactogen (r = 0.715) during mid and late (20 to 40 weeks) gestation. Inhibin levels in umbilical vein serum (38.5 +/- 1.3 U/ml, n = 5) were not different from those in umbilical artery serum (39.4 +/- 3.6 U/ml) but were significantly (p less than 0.01) lower than those in maternal serum (50.9 +/- 5.3 U/ml), which was obtained at the time of delivery. By day 5 of puerperium, serum levels of inhibin in the maternal vein were extremely low (2.3 +/- 0.1 U/ml, n = 7); these levels were nearly one fifth lower than follicular phase levels of 10.9 +/- 3.4 U/ml (n = 38). We propose that maternal inhibin in early gestation is secreted from the corpus luteum of pregnancy but that increasing inhibin levels during mid and late gestation result from inhibin that is produced by the placenta. The lack of an umbilical arterial-venous gradient for inhibin and the higher levels of inhibin in maternal serum argue against a fetal source of inhibin in the maternal circulation. The physiologic function of inhibin that is produced by the corpus luteum and by the placenta remains to be determined.

Direct effects of human uremic serum on the production of endothelin-1 in cultured porcine endothelial cells were examined in this study. Uremic serum decreased the level of monomeric endothelin-1 secreted into the culture medium by endothelial cells. This effect occurred at a transcriptional step because uremic serum decreased the endothelin-1 mRNA level in those cells. For the partial characterization of this inhibitory activity, uremic serum was fractionated with a centricut column. Uremic serum contains humoral factor(s) larger than 50 kD which suppress the endothelin-1 mRNA level in cultured endothelial cells.

Erythropoietin (Epo) titers in the aged (from 70 to 89 years) were determined by a radioimmunoassay. Epo levels in normal elderly subjects were not different from levels in the young volunteers. The serum Epo levels in elderly patients with anemia were inversely related to hemoglobin levels; their regression coefficient was not worse than that found in young patients. It is suggested that the reactivity of Epo production to anemia in the aged may not be worse than that reactivity in the young.

A murine monoclonal antibody designated 1G12 has been produced by immunizing mice with A549 human lung adenocarcinoma. Using radiolabeled monoclonal antibody 1G12, a sensitive radioimmunoassay to detect 1G12 antigen has been developed. The antigen was detected on the surface of peripheral blood mononuclear cells (PBMC). A study was performed to examine the frequency of distribution of this antigen on the surface of PBMC from healthy donors and patients with cancer. An antigen level of above 30 units per 1 x 10(6) PBMC was considered positive. None of 41 healthy donors (0%) and 16 of 96 patients (16.7%) with benign diseases of the lung, ovary, and uterus were positive. In contrast, 27 of 41 patients (65.8%) with lung cancer, 14 of 18 patients (77.8%) with ovarian cancer, and 16 of 27 patients (59.2%) with uterine cervical cancer had elevated levels of 1G12 antigen. When patients were grouped by stages of cancer, PBMC from patients in relatively early stages (stages I and II) also gave positive results, i.e., 9 of 17 patients (59.2%) with lung cancer, 6 of 10 patients (60%) with ovarian cancer, and 11 of 22 patients (50%) with uterine cervical cancer of these stages were positive. These results suggest that the detection of 1G12 antigen on PBMC of patients may be useful for early diagnosis of cancers.

The major acidic polysaccharide, named saposhnikovan A, was isolated from the roots and rhizomes of Saposhnikovia divaricata. It showed remarkable reticuloendothelial system-potentiating activity in a carbon clearance test. It is composed of L-arabinose: D-galactose: D-galacturonic acid in the molar ratio of 6:15:10, and its molecular weight was estimated to be 54000. About 35% of the D-galacturonic acid residues exist as the methyl esters. Methylation analysis, 13C-nuclear magnetic resonance, and controlled Smith degradation studies indicated that the polysaccharide has the alpha-1----4-linked D-galacturonan backbone bearing alpha-1----5-linked L-arabino-beta-3,6-branched D-galactan side chains.