[Correlation between weight variability and the risk of diabetic nephropathy in patients with type 2 diabetes mellitus].

Objective: To evaluate the relationship between different indexes of weight variability and the risk of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: A retrospective cohort study. The clinical data of 2 180 T2DM patients without DKD who underwent case management at Lee's United Clinic in Taiwan, China from 2002 to 2018 were retrospectively analyzed, including 1 103 females and 1 077 males, with an average age of (64.8±12.4) years. Regular follow-up was conducted for patients for at least 2 years, and their metabolic indexes were monitored annually. BMI variability independent of the mean (BMI-VIM), average yearly mean square successive difference (BMI-ASV), coefficient of variation (BMI-CV) and standard deviation (BMI-SD) were calculated,based on the body mass index (BMI) recorded annually by the patients. Patients were divided into four groups (Q1-Q4) based on the quartiles of the four weight variability indexes. DKD group and non-DKN group(NDKD group) were defined based on the occurrence of DKD at the end of the follow-up. Cox proportional hazards regression models were used to analyze the relationship between the four weight variability indicators and the incidence of DKD. Subgroup analysis was performed by categorizing patients into non-obesity (BMI<28 kg/m2) and obesity groups (BMI≥28 kg/m2) to investigate the impact of the four weight variability indicators on the risk of DKD. Results: After a follow-up of (4.55±2.13) years, 904 patients developed DKD. Compared with the NDKD group, patients in the DKD group had a higher proportion of females, older age, longer duration of diabetes, more insulin users, higher waist-to-hip ratio, higher levels of BMI-VIM, BMI-ASV, BMI-CV, BMI-SD, systolic blood pressure, diastolic blood pressure, and urine albumin-creatinine ratio, a lower proportion of hypoglycemic drugs, estimated glomerular filtration rate, and high-density lipoprotein cholesterol level, with statistically significant differences between the two groups(all P<0.05). Cox proportional hazards regression analysis results revealed that the risk of DKD in T2DM patients increased with the increase in BMI-SD, BMI-CV, BMI-VIM, and BMI-ASV after correcting a series of influencing factors. In the BMI-VIM subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.4% [HR=1.224 (95%CI:1.008-1.487), P=0.041]. In the BMI-ASV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 51.1% [HR=1.511 (95%CI:1.240-1.841), P<0.01]. In the BMI-CV group, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.006-1.485), P=0.044]. In the BMI-SD subgroup, compared with the Q1 group, the risk of DKD in the Q4 group increased by 22.2% [HR=1.222 (95%CI:1.002-1.490), P=0.048]. Sub-group analysis showed that when the non-obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.551 (95%CI:1.228-1.958), P<0.001];when the obesity group was grouped by BMI-ASV, after correcting a series of influencing factors, compared with the Q1 group, the highest risk of DKD occurred in the Q4 group [HR=1.703 (95%CI:1.168-2.485), P=0.006]. Conclusion: Increases in BMI-VIM, BMI-ASV, BMI-CV, and BMI-SD are associated with an increased risk of DKD in T2DM patients.

Charge inhomogeneity of carbon.

Charge distribution on every atom of carbon matter in four dimension forms (cluster, fullerene, atomistic carbon chain, nanotube, graphene, surface and solid) was investigated by the first-principles calculation. It is found that the charge distribution in most of these materials is inhomogeneous, even in one certain solid phase. We found that if one atom in carbon has different surrounding environment from another one nearby, they always have electron transfer, that is, they have different charge. In round C10 ring, C24 and C60 fullerenes, charge is zero, while charge is not zero in pentagon C10 ring, C30 and C70 fullerenes. At the ends of atomistic chains, nanotube or on the edges of graphenes, carbon atoms have larger positive or negative charge, while almost zero in the central parts. Charge is zero in diamond and graphite, while it is not zero in the high pressure solid phase hexagonite or on some carbon surfaces. The non-zero charge in carbon possibly means its non-zero valence.

Effects of vitamin D or its analogues on the mortality of patients with chronic kidney disease: an updated systematic review and meta-analysis.

The objective of this study was to assess whether vitamin D (VD) treatment alters the overall all-cause and cardiovascular mortalities in a chronic kidney disease (CKD) population. We systematically searched PubMed, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials without language restriction, until the publication date of 22 February 2016. All related literatures that compared VD treatment with non-VD treatment and reported the mortality of patients with CKD (including those undergoing dialysis) were identified. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated by using the random- and fixed-effects models. Randomised controlled trials (RCTs) that used the intention-to-treat principle and observational studies (OSs) were analysed separately. For this study, 38 studies involving 223 429 patients (17 RCTs, n=1819 and 21 OSs, n=221610) were included. In the OSs, VD treatment was significantly associated with reductions in both all-cause and cardiovascular mortalities; however, such significant association was not found in the RCTs. The existing RCTs do not provide sufficient or precise evidence that VD supplementation affects the mortality of patients with CKD, although subsets of patients that could potentially benefit from VD treatment can be identified by using the existing data from the RCTs. Nevertheless, large-size RCTs are needed in the future to assess any potential differences in survival prospectively.

[Effect of serum interleukin-21 on B cell secretory capacity and apoptosis in patients with systemic lupus erythematosus].

Objective: To investigate the secretory capacity and apoptosis of interleukin (IL)-21 induced normal B cells by co-culture with serum from patients with systemic lupus erythematosus (SLE). Methods: Serum from twenty new-onset SLE patients and 20 healthy donors were collected. CD(19)(+) B cells from the normal controls were co-cultured with serum from SLE patients in the presence or absence of IL-21-R-FC(4 µg/ml). Supernatant IgG and IgM concentration were measured by immunoturbidimetric assay on day 5. Supernatant anti-dsDNA level was determined by ELISA. The percentage of apoptotic cells was detected by flow cytometer. Results: IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum were significantly higher than those in the serum of SLE patients alone [(5.84±1.79)g/L vs (4.25±1.48)g/L, P=0.000; (0.46±0.21)g/L vs (0.43±0.21)g/L, P=0.003; (127.76±70.24)IU/ml vs (115.15±63.88) IU/ml, P=0.014 respectively]. However, no significant differences were found in the group of normal B cells with non-homologous serum from normal controls (P>0.05). Supernatant IgG, IgM and anti-dsDNA levels in normal B cells with SLE serum significantly decreased while IL-21R-fusion protein was added [(5.26±1.62)g/L vs (5.84±1.79)g/L, P=0.006; (0.42±0.20)g/L vs (0.46±0.21)g/L, P=0.002; (118.00±69.62)IU/ml vs (127.76±70.24)IU/ml, P=0.012 respectively]. The apoptotic rate of B cells with SLE serum was significantly higher than that with normal serum [(47.88±12.65)% vs (38.86±10.32)%, P=0.004]. But adding IL-21R-fusion conversed the apoptotic rates [(42.08±12.52)% vs (47.88±12.65)%, P=0.001]. Conclusions: SLE serum could induce normal B cells to form immunoglobulin secreting cells and producing autoantibodies, or apoptosis in pathological conditions. IL-21 might be considered as a potential therapeutic target of SLE.

Expressions of BAFF/BAFF receptors and their correlation with disease activity in Chinese SLE patients.

B-cell activating factor belonging to tumour necrosis factor family (BAFF) is essential for B-cell survival and function through interaction with its receptors BAFF receptor 3 (BR3), B-cell maturation antigen (BCMA) and/or transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), though BCMA and/or TACI can also bind to a proliferation-inducing ligand (APRIL). We evaluate the correlation of the expressions of these ligands/receptors with different clinical manifestations of systemic lupus erythematosus (SLE). Levels of BAFF and APRIL in plasma from 73 SLE patients were determined by enzyme-linked immunosorbent assay. Expressions of BR3, TACI and BCMA on CD19+ B cells were detected by flow cytometry. Clinical data were collected and disease activity was evaluated using SLEDAI-2000. SLE patients had elevated BAFF and APRIL levels in their plasma. BAFF levels correlated positively with SLEDAI while negatively with the BR3 protein expression on CD19+ B cells (p < .05). The detected BR3 protein expression in SLE patients was reduced on CD19+IgD+CD27-, CD19+IgD+CD27+ as well as CD19+IgD-CD27+ B cells compared to the counterparts of healthy controls (p < .001), whereas SLE patients did not differ from healthy controls in BR3 mRNA levels. In untreated new-onset patients, the expression rate of BR3 on CD19+ B cells correlated negatively with SLEDAI (p < .05). Elevation of BAFF and reduction of BR3 on CD19+ B cells were more obvious in those with lupus nephritis (LN, p < .05). TACI expression on CD19+ B cells was up-regulated only in those subjects with LN (p < .05). Elevated plasma BAFF and reduced BR3 protein expression on peripheral B cells could act as biomarkers for active disease in SLE patients. High expression of TACI may indicate the occurrence of LN.

Enhanced selectivity screening of GPCR ligands using a label-free cell based assay technology.

Drug discovery efforts advance in step with advancements in assay technologies, as new technologies provide new lenses through which biology can be viewed. The novel information gathered results in the better understanding of drug-target interactions leading to better decision making during the drug discovery process. One area of rapid development is within label-free technologies. Label-free technologies offer many distinct advantages to the drug discovery workflow. One such novel technology is the CellKey System, an impedance-based label-free live cell assay platform. The system is based on impedance technology and is a universal platform for the functional measurement of all classes of G-protein coupled receptors (GPCRs). Data are generated in a kinetic fashion on both endogenously expressed and transfected receptors in a wide variety of cell types. In the studies detailed here, we used the system to perform an enhanced selectivity screen of a small panel of compounds simultaneously against two unrelated GPCR targets signaling through different pathways. Utilizing both the quantitative measures of cellular activation and the qualitative information inherent in the rich output data, we gained knowledge not only about the relative selectivity of each compound across both targets, but also about the character of the interaction of each with the cellular target. In this manner, we successfully demonstrated proof of principal for using an impedance-based technology to perform selectivity analyses and to triage lead compounds in a simplified format.

Clinical features and outcome of neuropsychiatric lupus in Chinese: analysis of 240 hospitalized patients.

Neuropsychiatric (NP) events are severe manifestations of systemic lupus erythematosus (SLE) and relate to poor outcome. The aims of this study are to investigate the NP manifestations of SLE and to identify the predictive factors for clinical outcome. There was a retrospective review of 240 hospital patients with primary NP events of SLE (NPSLE) from 1990 to 2004. Neuropsychiatric manifestations, SLE disease activity index (SLEDAI) score, System lupus International Collaborating Clinic/American College of Rheumatology Damage Index (SLICC/ACR-DI) score, magnetic resonance imaging (MRI) findings, treatment and mortality rate were included for analysis. From this group of patients, 15 NP syndromes were identified. The most frequent manifestation was headache, followed by seizure. The mean SLEDAI and SLICC/ACR-DI scores were 19.9 +/- 6.9 and 3.5 +/- 1.6, respectively. Abnormal MRI features were found in 67% (61/91) patients. At least one intrathecal (IT) injection of methotrexate (MTX) plus dexamethasone (DXM) was administered to 109 (45.4%) patients. High dose (1 g) intravenous methylprednisolone pulse therapy (IVMP) was administered to 167 (69.5%) patients. Multifactor analysis revealed that high SLICC/ACR-DI scores and sets of concurrent NP symptoms were independently associated with poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM were protective factors against poor outcome. From our data, NPSLE is heterogeneous and is usually associated with high disease activity and organ damage scores. High SLICC/ACR-DI score and having more than two sets of NP symptoms are the predictors for poor outcome, whereas pulse IVMP and IT injection of MTX plus DXM can improve the prognosis.

Clinical significance of increased CD4+CD25-Foxp3+ T cells in patients with new-onset systemic lupus erythematosus.

OBJECTIVE: To investigate the expressions of Foxp3 and CD25 on CD4(+) T cells from patients with new-onset systemic lupus erythematosus (SLE) and assess their clinical significance. METHODS: 10 patients with active (systemic lupus erythematosus Disease Activity Index (SLEDAI) >or=10) and 11 with inactive (SLEDAI 0.05). Moreover, the suppressive capacity of CD4(+)CD25(+)T cells in patients with new-onset lupus was not impaired as measured by the ability to inhibit proliferation of CD4(+)CD25(-) T cells. Interestingly, CD4(+)CD25(-)Foxp3(+ )T cells in new-onset lupus (2.97-10.94%) were significantly more frequent than in normal controls (1.01-3.62%) (p<0.01), and correlated positively with the titres of anti-dsDNA antibodies (p = 0.029). Few of these cells expressed CD127. Treatment with glucocorticoids and cyclophosphamide reduced CD4(+)CD25(-)Foxp3(+) T cells in 8 of 10 patients with active disease. CONCLUSIONS: There was a significant increase in CD4(+)CD25(-)Foxp3(+)T cells in patients with new-onset SLE that correlated with anti-dsDNA titres, whereas no alteration in either the percentage or function of CD4(+)CD25(+)Foxp3(+)T cells was observed.

Adaptive segmentation of cerebrovascular tree in time-of-flight magnetic resonance angiography.

Accurate segmentation of the human vasculature is an important prerequisite for a number of clinical procedures, such as diagnosis, image-guided neurosurgery and pre-surgical planning. In this paper, an improved statistical approach to extracting whole cerebrovascular tree in time-of-flight magnetic resonance angiography is proposed. Firstly, in order to get a more accurate segmentation result, a localized observation model is proposed instead of defining the observation model over the entire dataset. Secondly, for the binary segmentation, an improved Iterative Conditional Model (ICM) algorithm is presented to accelerate the segmentation process. The experimental results showed that the proposed algorithm can obtain more satisfactory segmentation results and save more processing time than conventional approaches, simultaneously.

[Micro determination of acrylonitrile in ambient air by gas chromatography].

Acrylonitrile in ambient air was collected by Tenax GC and then thermo-desorbed. It was separated on GDX-502 chromatographic column from other pollutants and determined by flame-ion ization detector. The minimum detectable concentration was 0.01 mg/m3 when 2 L ambient air was collected. The recoveries were 85.6%-105.4% and RSDs were 4.5%-6.2%.

Analogues of the potential antipsychotic agent 1192U90: amide modifications.

Analogues of 2-amino-N-(4-(4-(1,2-benzisothiazol-3-yl)-l-piperazinyl) -butyl)benzamide hydrochloride (1192U90) were prepared and evaluated in receptor binding assays for the dopamine D2, serotonin 5-HT1a, and serotonin 5-HT2 receptors. Eight compounds have been synthesized in which the amide group of 1192U90 has been replaced with a variety of functional groups (i.e. ester, ketone, thioamide, butyramide, butyranilide, sulfonamide, alkoxyamide and hydrazide). These compounds exhibited moderate to potent affinities (0.55-200 nM) for all three receptors. Several analogues exhibited improved selectivity for the 5-HT2 receptor with D2/5-HT2 binding ratios greater than 1192U90.

Decreased T cell response to anti-CD2 in systemic lupus erythematosus and reversal by anti-CD28: evidence for impaired T cell-accessory cell interaction.

OBJECTIVE: To assess the ability of T cells from patients with systemic lupus erythematosus (SLE) to respond to a mitogenic combination of anti-CD2 monoclonal antibodies (MAb), and to learn the molecular basis of the documented defect. METHODS: Peripheral blood mononuclear cell (PBMC) populations from individuals with SLE and paired controls were stimulated in vitro with anti-CD2, and the proliferative response was compared with that evoked by stimulation with phytohemagglutinin (PHA) and anti-CD3. Surface markers on lymphocyte populations were assessed by flow cytometry after staining with specific MAb. RESULTS: The proliferative response to anti-CD2 was decreased to a greater extent than was the response to anti-CD3 or PHA in SLE patients. This defect was found in approximately one-half of the patients examined, was not associated with disease activity, and was maintained upon repeated testing. Since either monocytes or resting B cells can serve as accessory cells for T cells following activation by anti-CD2, we examined the T cell response after depletion of adherent cells. In approximately two-thirds of the individuals with a decreased response, depletion of monocytes or substitution of monocytes with allogeneic, resting B cells from normal donors corrected the defect. The addition to PBMC of anti-CD28, but not of a neutralizing antibody to interleukin-10, largely reversed the anti-CD2 proliferative defect. Significantly fewer CD8+ T cells expressed CD28 in SLE, and this defect was also documented, to a lesser extent, in CD4+ cells. CONCLUSION: This study provides evidence that some functional T cell defects in SLE may be due, at least in part, to decreased CD28-mediated costimulatory activity following the interaction of T cells with conventional accessory cells.

Preclinical neurochemical and electrophysiological profile of 1192U90, a potential antipsychotic.

11192U90 was submitted to receptor binding and monoamine uptake assays. It bound potently at serotonin 5-HT2, dopaminergic D2, serotonin 5-HT1A, and adrenergic alpha 1 and alpha 2 receptors. It also bound to dopaminergic D1, serotonin 5-HT3, serotonin 5-HT4, and sigma sites, albeit with lower affinity. It was essentially inactive at 22 other sites, including those for cholinergic M1 and M2. It weakly inhibited uptake of 3H-norepinephrine, 3H-serotonin and 3H-dopamine. Acute doses of 1192U90 (5 and 20 mg/kg P.O.) increased whole-brain levels of dopamine metabolites but did not affect levels of norepinephrine, dopamine, and serotonin. Subcutaneous injection of 1192U90 (0.8 mg/kg/day) and clozapine (20 mg/kg/day) for 28 days preferentially decreased the number of spontaneously active dopamine cells in the ventral tegmental area (VTA) but not the substantia nigra (SN) of rats, as measured by population sampling. This outcome is characteristics of atypical antipsychotics like clozapine. Acute injections of 1192U90 reversed the rate-inhibiting effects of microiontophoretically applied dopamine and intravenously injected apomorphine and d-amphetamine on dopamine cell firing. Intravenous injection or iontophoretic application of 1192U90 or the 5-HT1A agonist (+/-)8-OH-DPAT inhibited the firing rates of dorsal raphe nucleus (DRN) neurons in rats, and the effects of both compounds were blocked by iontophoretically applied S(-) propranolol, a 5-HT1A antagonist. The results suggest that 1192U90 is a preferential dopamine D2 antagonist as well as a 5-HT1A agonist that may prove to be an atypical antipsychotic.

[The trend of proportion among inpatients with gout in 21 hospitals during the past 15 years].

We analyzed data gathered from 21 hospitals in our country from 1979 to 1993 on the total number of hospitalized patients with the number of gout patients. Results showed that the proportion of hospitalized gout patients in 21 hospitals has increased sharply during the past 15 years (Chi2 = 823.4, P < 0.001). The constituent ratio of hospitalized gout patients in 13 hospitals in southern China increased abruptly (Chi2 = 650.9, P < 0.001); while the constituent ratio in 8 hospitals in northern China increased to a lesser extent (Chi2 = 188.1, P < 0.001). A significant difference was noticed between southern and northern China (Chi2 = 45.8, P < 0.001). During the past 15 years, the proportion of hospitalized gout patients has been increasing rapidly, with greater extent in the south. This is probably related to the economic development which improves the standard of living and to the changes of food structure.

4-(Heteroarylthio)-2-biphenylyltetrazoles as nonpeptide angiotensin II antagonists.

A series of 4-(heteroarylthio)-2-biphenylyltetrazoles was prepared, and the compounds were examined for their ability to displace [3H]AII from angiotensin II receptors. Analogues that exhibited significant receptor binding affinities at less than 10 microM were investigated further for potential antagonism of angiotensin II-mediated contraction of rabbit isolated aortic rings. Three 4-(heteroarylthio)-2-biphenylyltetrazoles were identified that exhibited sub-micromolar angiotensin II receptor binding affinities. These compounds and two reference agents, saralasin and losartan (DUP-753), exhibited concentration-dependent reversal of angiotensin II contraction in isolated aortic rings parallel to their receptor binding affinities. Molecular modeling studies were conducted to examine the conformational effects of the novel sulfide bridging unit contained in these 4-(heteroarylthio)-2-biphenylyltetrazoles. The biological effects of the sulfide bridge as well as alterations in the heteroaromatic moiety were investigated, and the resulting structure--activity relationships are discussed.

[CD2-mediated T-lymphocyte proliferation in patients with systemic lupus erythematosus].

PBMC proliferation in patients with SLE was assessed by incorporation of 3H-Tdr in an accessory cell-dependent response to anti-CD2 specific monoclonal antibody. The response was compared to monoclonal anti-CD3 and PHA response. There was a marked decrease in the response to anti-CD2 in SLE patients (9257 +/- 8543) than in normal controls (20619 +/- 15279) (P < 0.005). It was more obvious in 8 patients with less active and untreated disease, but not in 10 patients with less active or inactive disease. In contrast, no statistical difference was noted in the response to anti-CD3 and PHA between SLE patients and normal controls. We also examined the response of purified T cells to anti-CD2 and the response was depressed in SLE, but no marked decrease in the response to anti-CD3 was found in SLE patients. Our results demonstrate that SLE patients with active disease have T cells that respond poorly to CD2 activation, but that response via the CD3/TCR complex is essentially intact. It might be reflect intrinsic T cell defects in some SLE patients.

[The purification of SS-B antigen and detection of anti-SS-B antibodies].

SS-B antigen was purified from fresh rabbit thymus by ammonium sulfate precipitation and column chromatography with Sephadex G100 and phosphocellulose. The M. W. of SS-B is ranged at 41,000 to 48,000. It does not contain the other extractable antigens, like Sm, RNP, PM-ScL, Scl-70, Jo-1, and PCNA. The purified SS-B antigen only reacts with the CDC standard serum of anti-SS-B antigen only reacts with the CDC standard serum of anti-SS-B antibody by ELISA. The positive rate of the antibodies being 55.1%, 48.3%, 32.8%, 30.8% and 26.3% in SS, SLE, RA, PSS and MCTD respectively. The titers of anti-SS-B antibodies were higher in SS and SLE patients than other connective tissue disease patients. It was found that all of the anti-SS-B antibodies detected were mainly of IgG isotype. Preliminary analysis of clinical date shows that there is no relationship between anti-SS-B antibody and systemic involvement in SS.

The 1958 and 1987 ARA revised criteria for rheumatoid arthritis in Chinese patients. A comparative study.

The American Rheumatism Association (ARA) 1958 and 1987 criteria for the classification of rheumatoid arthritis (RA) were applied to 111 consecutive RA patients and 54 patients with non-RA connective tissue diseases from three hospitals of tertiary level in Beijing. Comparison of the two criteria showed that the specificity was the same, being 88% for both, whereas the sensitivity varied from 94% of the 1958 criteria to 91% of the 1987 criteria. Factors affecting the sensitivity were morning stiffness for more than one hour and increase of number of swollen joints from one to three in the 1987 revised criteria.

[Detection and clinical significance of anti-histone antibody in systemic lupus erythematosus and rheumatoid arthritis].

Determinations of anti-histone antibodies (AHA) by ELISA were carried out in 109 cases of SLE, 117 of RA, the positive rate being 50.5%, 23.1% respectively, with titres in SLE patients higher than in RA. AHA was 90.2% positive in active cases of SLE patients. SLE patients with AHA showed a higher incidence of pericarditis and arthritis, but a lower rate of malar rash than SLE patients without AHA. In RA, there is a higher incidence of extraarticular manifestations in AHA positive patients IgM-AHA was this predominant AHA in RA while in SLE patients it was the IgG-AHA. For SLE, IgG-AHA which was more closely associated with anti-ds DNA was more significant than IgM-AHA.

Pseudoautoimmunity in normal mice: anti-histone antibodies elicited by immunization versus induction during graft-versus-host reaction.

Native preparations of evolutionarily conserved intracellular macromolecules are generally nonimmunogenic when injected in soluble form. However, vigorous immune responses were observed when common autoantigens such as histones, DNA or Sm antigen, or homologous liver homogenate were noncovalently coupled to latex beads prior to injection into mice. Antibody response to histone beads displayed immunologic memory and required a functional thymus, suggesting that T-helper cells were involved. However, bead-elicited autoantibodies could be distinguished from true autoantibodies in that they reacted with denatured, minor, or foreign components of the preparations or to regions unexposed in the native form of the immunogen. This response contrasted with spontaneously arising autoantibodies accompanying graft-versus-host (GVH) disease in the same strain of mice which preferred native nucleoprotein conformations within nuclei, chromatin, or DNA-histone complexes. Histone beads elicited antihistone antibodies displaying a sustained IgM isotype in contrast to spontaneously arising autoantibodies in GVH disease which were predominantly IgG. These studies demonstrate that immunization with autoantigens does not usually elicit true autoantibodies and suggest that lymphocyte populations responsible for pseudoautoimmune responses are different from autoantibody-producing cells. We speculate that if autoimmunity is driven by particulate forms of in vivo self-materials, additional factors are required for breaking the natural tolerance to native conformations within the immunogen.