Eperisone Hydrochloride, a Muscle Relaxant, Is a Potent P2X7 Receptor Antagonist.

Eperisone Hydrochloride was launched in Japan in 1983 and has been used to improve muscle tone and treat spastic paralysis (Originator: Eisai Co., Ltd.). However, its biochemical mechanism of action is unknown. SB Drug Discovery was used to evaluate purinergic P2X (P2X) receptor antagonism using fluorescence. In this study, we discovered that its target protein is the P2X7 receptor. Also, P2X receptor subtype selectivity was high. This finding demonstrates the (Eperisone-P2X7-pain linkage), the validity of P2X7 as a drug target, and the possibility of drug repositioning of Eperisone Hydrochloride.

Selenium deficiency and scurvy due to an imbalanced diet of snacks and lacto-fermenting drinks: a case report of a 7-year-old boy with autism spectrum disorder.

BACKGROUND: There have been reports of isolated trace elements or vitamin deficiencies due to imbalanced diets, but no cases of selenium deficiency combined with scurvy have been reported. CASE PRESENTATION: A 7 year-old boy diagnosed with autistic spectrum disorder and mild psychomotor retardation, started an imbalanced diet including specific snacks and lacto-fermenting drinks from 5 years of age. Gingival hemorrhage and perioral erosions occurred at 6 years and 8 months of age, and he was referred to our hospital at 7 years of age. Slight tachycardia was found. Serum vitamin C level was 1.1 µg/dL (reference range (rr): 5-17.5 µg/dL), and selenium level was 2.8 µg/dL (rr: 7.7-14.8 µg/dL). He was diagnosed with both selenium deficiency and scurvy. Multivitamins and sodium selenate were administered for 12 days during admission, and symptoms of selenium deficiency and scurvy improved. After discharge, symptoms abated following the administration of multivitamins and regular administration of sodium selenate every 3 months. CONCLUSIONS: We report a complicated case of both selenium deficiency and scurvy due to an imbalanced diet of snacks and lacto-fermenting drinks in a 7-year-old boy with autism spectrum disorder. In patients with imbalanced diet, regular blood tests including trace elements and vitamins are necessary.

Paleoceanography of the northwestern Pacific across the Early-Middle Pleistocene boundary (Marine Isotope Stages 20-18).

The fluctuating position of the boundary between the Kuroshio (warm) and Oyashio (cold) currents in the mid-latitude western North Pacific affects both heat transport and air-ocean interactions and has significant consequences for the East Asian climate. We reconstruct the paleoceanography of Marine Isotope Stages (MIS) 20-18, MIS 19 being one of the closest astronomical analogues to the present interglacial, through multiple proxies including microfossil assemblage data, planktonic foraminiferal isotopes (δ18O and δ13C), and foraminiferal Mg/Ca-based temperature records, from the Chiba composite section (CbCS) exposed on the Boso Peninsula, east-central Japan. Principal component analysis (PCA) is used to capture dominant patterns of the temporal variation in these marine records, and shows that the relative abundances of calcareous nannofossil and radiolarian taxa are consistent with the water mass types inferred from geochemical proxies. The leading mode (36.3% of total variance) mirrors variation in the terrestrial East Asian winter monsoon (EAWM), reflecting seasonal trends dominated by the winter monsoon system. In the CbCS, this mode is interpreted as reflecting the interplay between the warm Kuroshio and cold Oyashio waters, which is likely related to the latitudinal shift of the subtropical-subarctic gyre boundary in the North Pacific. The second mode (15.4% of total variance) is closely related to subsurface conditions. The leading mode indicates that MIS 19b and 19a are represented by millennial-scale stadial/interstadial oscillations. Northerly positions for the gyre boundary during late MIS 19c, the interstadials of MIS 19a, and early MIS 18 are inferred from the leading mode, which is consistent with a weak EAWM and consequent mild winter climate in East Asia. Nonetheless, the northerly positions for the gyre boundary during late MIS 19c and early MIS 19a were not associated with subsurface warming presumably due to the suppressed gyre circulation itself caused by the weak Aleutian Low. Intermittent southerly positions for the gyre boundary are inferred for the stadials of MIS 19b and 19a. Regional sea surface temperature (SST) comparisons in the western North Pacific reveal that the moderate SSTs during MIS 19a through early MIS 18 were restricted to the mid- to high latitudes, influenced by the weak EAWM. Comparison between MIS 20-18 and MIS 2-1 suggests that glacial MIS 20 and 18 had significantly milder winters than MIS 2, likely related to the relatively weak EAWM. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40645-020-00395-3.

Paleoceanography and dinoflagellate cyst stratigraphy across the Lower-Middle Pleistocene Subseries (Calabrian-Chibanian Stage) boundary at the Chiba composite section, Japan.

A dinoflagellate cyst record from the highly resolved Chiba composite section in Japan has been used to reconstruct sea-surface paleoceanographic changes across the Lower-Middle Pleistocene Subseries (Calabrian-Chibanian Stage) boundary at the global stratotype, constituting the first detailed study of this microfossil group from the Pleistocene of the Japanese Pacific margin. Cold, subarctic water masses from 794.2 ka gave way to warming and rapid retreat of the Subpolar Front at 789.3 ka, ~ 2000 years before the end of Marine Isotope Stage (MIS) 20. Throughout the fully interglacial conditions of MIS 19c, assemblages are consistent with warm sea surface temperatures but also reveal instability and latitudinal shifts in the Kuroshio Extension system. The abrupt dominance of Protoceratium reticulatum cysts between 772.9 and 770.4 ka (MIS 19b) registers the influence of cooler, mixed, nutrient-rich waters of the Kuroshio-Oyashio Interfrontal Zone resulting from a southward shift of the Kuroshio Extension. Its onset at 772.9 ka serves as a local ecostratigraphic marker for the Chibanian Stage Global Boundary Stratotype Section and Point (GSSP) which occurs just 1.15 m (= 1300 years) below it. An interval from 770.1 ka to the top of the examined succession at 765.8 ka (MIS 19a) represents warm, presumably stratified but still nutrient-elevated surface waters, indicating a northward shift of the Kuroshio Extension ~ 5 kyrs after the termination of full interglacial conditions on land. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40645-021-00438-3.

Long-tailed distributions of inter-event times as mixtures of exponential distributions.

Inter-event times of various human behaviour are apparently non-Poissonian and obey long-tailed distributions as opposed to exponential distributions, which correspond to Poisson processes. It has been suggested that human individuals may switch between different states, in each of which they are regarded to generate events obeying a Poisson process. If this is the case, inter-event times should approximately obey a mixture of exponential distributions with different parameter values. In the present study, we introduce the minimum description length principle to compare mixtures of exponential distributions with different numbers of components (i.e. constituent exponential distributions). Because these distributions violate the identifiability property, one is mathematically not allowed to apply the Akaike or Bayes information criteria to their maximum-likelihood estimator to carry out model selection. We overcome this theoretical barrier by applying a minimum description principle to joint likelihoods of the data and latent variables. We show that mixtures of exponential distributions with a few components are selected, as opposed to more complex mixtures in various datasets, and that the fitting accuracy is comparable to that of state-of-the-art algorithms to fit power-law distributions to data. Our results lend support to Poissonian explanations of apparently non-Poissonian human behaviour.

CO2-Gas-Responsive Liquid Marble.

Liquid marbles were prepared using a water droplet and nonprotonated hydrophobic poly(2-N,N-diisopropylaminoethyl methacrylate) (PDiPAEMA) powder. Although the nonprotonated PDiPAEMA was hydrophobic, PDiPAEMA became hydrophilic because of the protonation of the pendant tertiary amino groups under acidic conditions. Therefore, liquid marbles stabilized with PDiPAEMA powder could float on a neutral to basic water surface, but they immediately disintegrated on an acidic water surface. Furthermore, the liquid marbles floating on the water surface disintegrated in response to CO2 gas because the water became acidic as a result of carbonic acid formation.

Usefulness of positron emission tomography for differentiating gliomas according to the 2016 World Health Organization classification of tumors of the central nervous system.

OBJECTIVE: Positron emission tomography (PET) is important in the noninvasive diagnostic imaging of gliomas. There are many PET studies on glioma diagnosis based on the 2007 WHO classification; however, there are no studies on glioma diagnosis using the new classification (the 2016 WHO classification). Here, the authors investigated the relationship between uptake of 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG) on PET imaging and isocitrate dehydrogenase (IDH) status (wild-type [IDH-wt] or mutant [IDH-mut]) in astrocytic and oligodendroglial tumors according to the 2016 WHO classification. METHODS: In total, 105 patients with newly diagnosed cerebral gliomas (6 diffuse astrocytomas [DAs] with IDH-wt, 6 DAs with IDH-mut, 7 anaplastic astrocytomas [AAs] with IDH-wt, 24 AAs with IDH-mut, 26 glioblastomas [GBMs] with IDH-wt, 5 GBMs with IDH-mut, 19 oligodendrogliomas [ODs], and 12 anaplastic oligodendrogliomas [AOs]) were included. All OD and AO patients had both IDH-mut and 1p/19q codeletion. The maximum standardized uptake value (SUV) of the tumor/mean SUV of normal cortex (T/N) ratios for MET, CHO, and FDG were calculated, and the mean T/N ratios of DA, AA, and GBM with IDH-wt and IDH-mut were compared. The diagnostic accuracy for distinguishing gliomas with IDH-wt from those with IDH-mut was assessed using receiver operating characteristic (ROC) curve analysis of the mean T/N ratios for the 3 PET tracers. RESULTS: There were significant differences in the mean T/N ratios for all 3 PET tracers between the IDH-wt and IDH-mut groups of all histological classifications (p < 0.001). Among the 27 gliomas with mean T/N ratios higher than the cutoff values for all 3 PET tracers, 23 (85.2%) were classified into the IDH-wt group using ROC analysis. In DA, there were no significant differences in the T/N ratios for MET, CHO, and FDG between the IDH-wt and IDH-mut groups. In AA, the mean T/N ratios of all 3 PET tracers in the IDH-wt group were significantly higher than those in the IDH-mut group (p < 0.01). In GBM, the mean T/N ratio in the IDH-wt group was significantly higher than that in the IDH-mut group for both MET (p = 0.034) and CHO (p = 0.01). However, there was no significant difference in the ratio for FDG. CONCLUSIONS: PET imaging using MET, CHO, and FDG was suggested to be informative for preoperatively differentiating gliomas according to the 2016 WHO classification, particularly for differentiating IDH-wt and IDH-mut tumors.

Millennial-scale northern Hemisphere Atlantic-Pacific climate teleconnections in the earliest Middle Pleistocene.

Suborbital-scale climate variations, possibly caused by solar activity, are observed in the Holocene and last-glacial climates. Recently published bicentennial-resolution paleoceanic environmental records reveal millennial-scale high-amplitude oscillations postdating the last geomagnetic reversal in the Marine Isotope Stage (MIS) 19 interglacial. These oscillations, together with decoupling of post-reversal warming from maximum sea-level highstand in mid-latitudes, are key features for understanding the climate system of MIS 19 and the following Middle Pleistocene. It is unclear whether the oscillations are synchronous, or have the same driver as Holocene cycles. Here we present a high resolution record of western North Pacific submarine anoxia and sea surface bioproductivity from the Chiba Section, central Japan. The record reveals many oxic events in MIS 19, coincident with cold intervals, or with combined cold and sea-level fall events. This allows detailed correlations with paleoceanic records from the mid-latitude North Atlantic and Osaka Bay, southwest Japan. We find that the millennial-scale oscillations are synchronous between East and West hemispheres. In addition, during the two warmest intervals, bioproductivity follows the same pattern of change modulated by bicentennial cycles that are possibly related to solar activity.

Orientation Direction Control in Liquid Crystalline Photoalignable Polymeric Films by Adjusting the Free-Surface Condition.

Adjusting the free-surface condition facilely controls the in-plane and out-of-plane orientations in liquid crystalline polymer (LCP) films. Top coating with aromatic molecules onto LC polymethacrylate films with N-benzylideneaniline (NBA) or 4-methoxybiphenyl (MB) side groups (PNBAM or PMBM) and subsequent annealing generate a random planar orientation while simultaneously removing the coated aromatic molecules, whereas annealing noncoated films induces a homeotropic orientation of the mesogenic side groups. Additionally, irradiating a top-coated PNBAM film with linearly polarized (LP) 365 nm light induces an in-plane molecular reorientation of the NBA side groups without changing the orientation in the homeotropically oriented region. Changes in the surface topology of the LCP films due to the reorientation processes are investigated in detail. Inkjet coating with aromatic molecules and LP 365 nm light exposure precisely controls the in-plane and out-of-plane alignment pattern in a PNBAM film.

Relationship between spontaneous expiratory flow-volume curve pattern and air-flow obstruction in elderly COPD patients.

BACKGROUND: Assessment of the degree of air-flow obstruction is important for determining the treatment strategy in COPD patients. However, in some elderly COPD patients, measuring FVC is impossible because of cognitive dysfunction or severe dyspnea. In such patients a simple test of airways obstruction requiring only a short run of tidal breathing would be useful. We studied whether the spontaneous expiratory flow-volume (SEFV) curve pattern reflects the degree of air-flow obstruction in elderly COPD patients. METHODS: In 34 elderly subjects (mean ± SD age 80 ± 7 y) with stable COPD (percent-of-predicted FEV(1) 39.0 ± 18.5%), and 12 age-matched healthy subjects, we measured FVC and recorded flow-volume curves during quiet breathing. We studied the SEFV curve patterns (concavity/convexity), spirometry results, breathing patterns, and demographics. The SEFV curve concavity/convexity prediction accuracy was examined by calculating the receiver operating characteristic curves, cutoff values, area under the curve, sensitivity, and specificity. RESULTS: Fourteen subjects with COPD had a concave SEFV curve. All the healthy subjects had convex SEFV curves. The COPD subjects who had concave SEFV curves often had very severe airway obstruction. The percent-of-predicted FEV(1)% (32.4%) was the most powerful SEFV curve concavity predictor (area under the curve 0.92, 95% CI 0.83-1.00), and had the highest sensitivity (0.93) and specificity (0.88). CONCLUSIONS: Concavity of the SEFV curve obtained during tidal breathing may be a useful test for determining the presence of very severe obstruction in elderly patients unable to perform a satisfactory FVC maneuver.

Feasibility study on biweekly paclitaxel treatment as maintenance chemotherapy in advanced müllerian carcinoma.

AIM: To evaluate the feasibility of biweekly paclitaxel treatment as maintenance chemotherapy for patients with advanced müllerian carcinoma. METHODS: Thirty patients with stage III or IV ovarian, fallopian tube, and peritoneal cancers who underwent primary optimal surgery and standard 6 cycles of carboplatin/taxane-based chemotherapy and exhibited a complete clinical response were entered in this study. Paclitaxel 80 mg/m(2) was administered biweekly for 12 cycles. Patients were evaluated monthly for treatment-related toxicity. RESULTS: Four patients, including 3 disease progressions and 1 bone marrow suppression, came off the protocol therapy. Twenty-six (86.7%) patients received complete treatment. Although the major toxicity was neutropenia, most of those patients (27/30, 90.0%) did not experience grade 3 or 4 neutropenia. Twenty-four (80.0%) patients showed persistent grade 1 neuropathy and the remaining 6 (20.0%) did not as a result of prior therapy. However, none experienced neuropathy progression during or after the protocol therapy. Most (17/22, 77.3%) of the completely treated patients experienced a regression of symptoms during and after therapy. CONCLUSION: Biweekly paclitaxel therapy is well tolerated by patients with advanced müllerian carcinoma and is therefore acceptable as a candidate for maintenance chemotherapy in these patients.

Validity study of the standing test for imbalance and disequilibrium (SIDE): Is the amount of body sway in adopted postures consistent with item order?

The standing test for imbalance and disequilibrium (SIDE) is a discriminative measure developed for the purpose of identifying balance deficits that may cause falls. The purpose of the present study was to determine the validity of the sequence of postures used in SIDE. Subjects comprised 30 men with a mean (±standard deviation) age of 21.9±3.11 years (range 19-32 years) and 30 women with a mean age of 20.7±1.24 years (range 19-23 years). Center of pressure (COP) was measured using a stabilometer recording for 30s with a 20-Hz sampling frequency. The measurement postures that were similar to postures adopted in the SIDE were: standing with feet 20cm apart; standing with legs close and the insides of both feet touching; two tandem standing positions (with the dominant foot forward and with the non-dominant foot forward); and two single-leg standing positions (on the dominant foot and on the non-dominant foot). We calculated total path length and envelopment area of sway from the COP data. Statistical differences in means were determined using the Tukey-Kramer multiple comparison test. Results indicate that the orders of total path length and envelopment areas of sway in each posture were consistent with the item order of SIDE. Significant differences existed between the means of total path length and envelopment areas of sway in each posture (p<0.05), with the exception of both tandem standing positions and both one-leg standing positions. The item order of SIDE appears to show concurrent validity in terms of the amount of body sway in the adopted postures.

Olig2 is useful in the differential diagnosis of oligodendrogliomas and extraventricular neurocytomas.

A 42-year-old woman had suffered from headaches since April 2009. Computed tomography revealed a tumor with marked calcification in the left frontal lobe adjacent to the left anterior horn of the lateral ventricle. T1-weighted gadolinium-enhanced magnetic resonance imaging showed a well-enhanced tumor at the lesion. Dynamic methionine positron emission tomography showed no delayed methionine attenuation. Initial preoperative diagnosis was extraventricular neurocytoma (EVN). However, oligodendroglioma was determined upon a second diagnosis. The patient underwent total tumor removal. Hematoxylin and eosin staining showed the characteristic fried egg-like cells, round nuclei, and immunohistochemically, the tumor cells were positive for glial fibrillary acidic protein, synaptophysin, neuronal nuclear antigen, microtubule-associated protein 2 and Olig2. The MIB-1 labeling index was 20%, which suggested malignancy. Although these findings demonstrated that the tumor had glioneuronal character, it was difficult to differentiate between EVN and oligodendroglioma. There have been reports that Olig2 immunohistochemistry is generally positive in cases of oligodendroglioma, but not in cases of neurocytoma. We completed the diagnosis as oligodendroglioma. Subsequent electron microscopy results presented oligodendroglial but not neuronal characteristics. We concluded that Olig2 is useful in the differential diagnosis of oligodendrogliomas and EVNs.

A case of multicentric Castleman's disease having lung lesion successfully treated with humanized anti-interleukin-6 receptor antibody, tocilizumab.

This report presents the case of a patient demonstrating multicentric Castleman's disease (MCD) with a lung lesion that was successfully treated with an anti-interleukin-6 receptor antibody, tocilizumab in combination with corticosteroid and tacrolimus. A 43-yr-old female with abnormal shadows on a chest X-ray was referred to the hospital for further examination. She was diagnosed as having MCD based on the characteristic pathology of inguinal lymph node, lung lesions, laboratory data, and undifferentiated arthritis. Corticosteroid and rituximab therapy did not fully ameliorate the symptoms; thus, the therapeutic regimen was changed to include tocilizumab, oral corticosteroid and tacrolimus. This regimen resulted in clinical remission and the dose of tocilizumab and corticosteroid could be tapered. Tocilizumab in combination with corticosteroid and tacrolimus may therefore be a beneficial treatment regimen for lung lesions associated with MCD.

Form birefringence in intrinsic birefringent media possessing a subwavelength structure.

We theoretically investigate optical birefringence originating from subwavelength structures in intrinsic birefringent media. Assuming alternating layers of isotropic and anisotropic materials, the propagation of optical waves is simulated on the basis of the finite difference time domain method. Optical polarization changes throughout the structure reveal the birefringence of the layered structure as a whole. In addition, the birefringence is also analyzed on the basis of effective medium theory. The results indicate that the optical birefringence of the structure as a whole can be modified by the magnitude and direction of the intrinsic birefringence of the anisotropic layers. This theoretical prediction will be useful for micro- and nanofabrication in optical devices.

Effects of angiotensin on the expression of fibrosis-associated cytokines, growth factors, and matrix proteins in human lung fibroblasts.

BACKGROUND AND OBJECTIVES: Angiotensin (Ang) II plays an important role in fibrogenesis in various organs, including the lung. The aim of this study is to elucidate (i) the effects of Ang II on the expression of cytokines, growth factors or matrix proteins in normal human lung fibroblasts, and (ii) the inhibitory effects of an Ang II type 1 (AT1) receptor blocker, candesartan. METHODS: Normal human adult lung fibroblasts were cultured. Candesartan was added and the cells were incubated. All the cells in culture dishes were collected at day 0 and 2, and the cell numbers were counted using a Neubauer haemocytometer (Clay-Adams, Parsippany, NJ, USA). The cell proliferation rates at day 2 were calculated in comparison to those at day 0. Total cellular RNA was extracted for real-time quantitative PCR, or the culture supernatant was collected for either a Sircol assay or enzyme-linked immunosorbent assay (ELISA). Laser scanning confocal microscopy was used for analyzing the cells with and without prior exposure to candesartan. Comparisons between the means of multiple groups were analyzed by one-way analysis of variance (ANOVA) followed by Tukey's test or Games-Howell's test. Values of P < 0*05 were considered to be statistically significant. RESULTS: Among the 12 fibrosis-associated cytokines and growth factors, mRNA expressions of interleukin (IL)-4, IL-7, and platelet-derived growth factor-D were significantly modulated by Ang II, and suppressed by candesartan. Soluble collagen and elastin levels were significantly elevated by Ang II, and suppressed by candesartan. Under confocal microscopy, the intracellular distribution of elastin was significantly increased by Ang II, and suppressed by candesartan. CONCLUSION: These data indicate that Ang II promotes lung fibrosis by increasing the matrix formation, which was suppressed by AT1 receptor blocker.

Phase II study of intraperitoneal carboplatin with intravenous paclitaxel in patients with suboptimal residual epithelial ovarian or primary peritoneal cancer: a Sankai Gynecology Cancer Study Group Study.

PURPOSE: To assess the antitumor efficacy and safety of 2 treatment modalities: intraperitoneal carboplatin combined with intravenous (IV) paclitaxel. PATIENTS AND METHODS: Eligible patients were those with epithelial ovarian carcinoma or primary peritoneal carcinoma stages II to IV who underwent initial surgery and had a residual tumor size of 2 cm or larger. Patients received IV paclitaxel 175 mg/m followed by intraperitoneal carboplatin AUC6. The primary end point was a response. Secondary end points were toxicity, progression-free survival, and overall survival. RESULTS: Twenty-six patients were enrolled, and 24 patients were eligible for assessment. The response rate was 83.3% (95% CI, 62.6%-95.3%; ). The median progression-free survival was 25 months. The median overall survival had not been reached. Incidences of grade (G) 3/4 hematological toxicities were absolute neutrophil count, 96%; hemoglobin, 29%; and thrombocytopenia, 16%. Nonhematological toxicities included G2 liver function, 4%; G3 sensory neuropathy, 8%; and G3 myalgia and arthralgia, 4%. CONCLUSIONS: Intraperitoneal administration of carboplatin combined with IV paclitaxel was well tolerated and showed satisfactory response in the patients with bulky residual tumor. Large-scale phase III trial comparing with IV carboplatin is warranted in this patient population.

Tumor-associated macrophage/microglia infiltration in human gliomas is correlated with MCP-3, but not MCP-1.

The monocyte chemotactic protein 3 (MCP-3) belongs to the MCP subgroup of the CC chemokines and promotes chemotaxis of immune cells. MCP-1 is believed to play an important role in monocyte infiltration into tumor tissues; however, the relationship between tumor-infiltrating macrophage/microglia (TIM/M) and the expression of chemokines has not been investigated in detail in human glioma samples; therefore, we first examined the expression of several chemokines and chemokine receptors in human tumor cell lines, which included glioma lines, using real-time PCR. We found that several glioma lines expressed MCP-3 predominantly, and not MCP-1. In order to assess the significance of MCP-3 expression in human glioma tissues, we then examined the number of CD68+ TIM/M, the percentage of TIM/M in the total cell population, and the expression of MCP-1 and MCP-3 in glioma tissues. There was a correlation between the percentage of TIM/M and MCP-3 expression levels; however, there was no correlation between the percentage of TIM/M and MCP-1 expression. There was no correlation between the number of TIM/M and prognosis of patients. These data indicate that tumor cell-derived MCP-3, but not MCP-1, facilitates the infiltration of macrophage/microglia into tumor tissues. This is the first study that clearly compared the significance of MCP-3 with that of MCP-1 in the tumor infiltration rates of TIM/M.

The relationships between titers of anti-Ro or anti-La as measured by ELISA and salivary production rate with age correction.

The objective of this work was to clarify the clinical significance of titers of anti-Ro and anti-La, the relationships between titers of either anti-Ro or anti-La, and salivary production rate (SPR). These autoantibodies were titrated using enzyme-linked immunosorbent assay. The Saxon test was performed to measure SPR. Fifty-one females who had anti-Ro but not anticentromere antibodies or anti-U1RNP were enrolled. SPR decreased significantly with age. In order to exclude the effect of aging on SPR, we calculated the "SPR with age correction." According to the results of a multiple regression analysis, only the anti-La titer was significantly associated with SPR with age correction. The distribution pattern of the anti-La titers consisted of two subgroups (with a titer index cutoff of 100.0): a negative anti-La titer (anti-La<25.0) and low anti-La titer (25.0or=100.0). The concentration of serum IgG and the frequency of Sjögren's syndrome in the high anti-La titer group were significantly higher than those in the negative anti-La and low anti-La titer group. Several new aspects of the clinical significance of titrating anti-Ro and anti-La in comparison with SPR have been revealed.

Negative correlation of anti-U1RNP antibody titers and the amount of salivary secretion with age correction.

OBJECTIVE: The aim of this study was to reveal whether or not the presence of anti-U1RNP antibodies is associated with a low amount of salivary secretion (ASS). SUBJECTS AND METHODS: Twenty females (mean age 49+/-12 years) who had anti-U1RNP but not ACA, anti-Ro, or anti-La antibodies (anti-U1RNP-positive group), and 65 control females (mean age 50+/-12 years) were included in this study. The saxon test was performed to measure the ASS. RESULTS: After a correction for age by ANCOVA, ASS in the anti-U1RNP-positive group was significantly lower than ASS in the control group (p <0.001). In the control group, ASS was not significantly decreased with advanced age (r=-0.140, p=0.211). In the anti-U1RNP-positive group, ASS was decreased with age, without a significant difference (r=-0.379, p=0.100). In the next analysis, we introduced 'ASS with age correction', assuming that all subjects in the anti-U1RNP-positive group were 49 years of age. A negative correlation between the titers of anti-U1RNP antibodies and the ASS with the age correction in the anti-U1RNP-positive group was noted (r=-0.520, p=0.019). The log of the antinuclear antibodies titers, or titers of rheumatoid factor was significantly correlated with the titers of anti-U1RNP antibodies, respectively (r=0.466, p=0.038 and r=0.595, p=0.006; respectively). The pathological findings of minor salivary gland biopsy in 2 subjects were compatible with Sjögren's syndrome; one subject showed moderate lymphocytic infiltration. CONCLUSION: The presence of anti-U1RNP antibodies is associated with reduced ASS.