Comparison of the anatomical dimensions and mechanical properties of the dorsoradial and anterior oblique ligaments of the trapeziometacarpal joint.

PURPOSE: The respective roles of the dorsoradial (DRL) and anterior oblique (AOL) ligaments in stability of the highly mobile trapeziometacarpal (TMC) joint remain disputed. Earlier publications have pointed to the AOL as the key stabilizing structure; yet, more recent publications have challenged the stabilizing role of the AOL, favoring the DRL as the main TMC joint stabilizer. We executed an anatomical study of the ligaments, including detailed dissection to quantify the length, width, and thickness of the AOL and DRL and tested the material properties of these ligaments. METHODS: Thirteen fresh frozen cadaveric thumbs from 9 specimens were used. Length, width, and thickness of the AOL and DRL were measured on magnetic resonance imaging and/or after dissection. Next, the first metacarpal and trapezium were isolated together with both ligaments, and both bones were cut sagittally to isolate a first metacarpal-AOL-trapezium and first metacarpal-DRL-trapezium complex from each thumb. These samples were subjected to cyclic loading in displacement-controlled tests. The obtained force-displacement curves were used to calculate stiffness and hysteresis of each sample. RESULTS: Our results showed that the DRL is significantly shorter and thicker than the AOL, which is thin and ill-defined. Our results also indicate that the DRL has a higher stiffness than the AOL, making it a more likely candidate to provide joint stability. CONCLUSIONS: Although the AOL has been asserted to be the primary restraint to dorsoradial subluxation, this view has been challenged over the past 10 years by several studies. These studies have shown the AOL to be relatively weak and compliant compared with the intermetacarpal and dorsoradial ligaments and have demonstrated that the DRL is the strongest and stiffest ligament of the TMC joint. Our studies confirm these findings. CLINICAL RELEVANCE: This study indicates that the DRL is relatively stiff and thick, suggesting it should be repaired or reconstructed when disrupted to restore stability of the TMC joint.

In vivo quantification of the 3D kinematics and coupling of the thumb base joints.

Full thumb mobility is required to execute tasks of daily living and results from the combined motions of the thumb joints. In this study, we focus on the coupling between the proximal joints of the thumb, the radioscaphoid (RS), scaphotrapezial (ST) and trapeziometacarpal (TMC) joints. We quantified the 3D kinematics of these joints during maximal thumb extension and abduction in a group of healthy volunteers using an image-based technique. Semi-dynamic CT scans of the dominant hand of 36 healthy subjects with the thumb in different standardized positions were used. The maximal range of motion of each joint in the different planes was calculated using a markerless bone registration method. Inter-joint coupling was assessed by performing a regression analysis between the range of motion of the joints during both thumb movements. Strong inter-joint coupling was found between the RS and ST joints during thumb extension and abduction, whereas coupling between the other joints was moderate to weak. This study provides valuable information on the in vivo 3D kinematics of the RS, ST and TMC joints during thumb movement. This can be used as input for modeling studies, where the coupling between the joints can decrease the degrees of freedom of the model. Moreover, these baseline data of a healthy cohort can be used for comparison with the kinematics of patients with TMC osteoarthritis or other pathologies and aid our understanding of motion deficits resulting from these joint disorders.

Anatomy and biomechanics of healthy and arthritic trapeziometacarpal joints.

Understanding the biomechanics of the trapeziometacarpal (TMC) or first carpometacarpal (CMC1) joint, the pathophysiology of basal thumb arthritis, the design and performance of surgical procedures require a solid anatomical basis. This review of literature summarizes the most recent data on the descriptive, functional, and comparative anatomy of healthy and arthritic TMC joints.

Liquid chromatography electrospray tandem mass spectrometric and desorption electrospray ionization tandem mass spectrometric analysis of chemical warfare agents in office media typically collected during a forensic investigation.

Most prior analytical studies have dealt with the determination of chemical warfare agents in environmental or biological matrices that would typically be collected following battlefield use or in support of the Chemical Weapons Convention. These methods may be useful for some investigations, but may not be practical for indoor forensic investigations where chemical warfare agent use is suspected. There is a need for analytical methods for chemical warfare agent identification in office media, including flooring, wall surfaces, office fabrics and paper products, which would typically be collected in an office environment during forensic investigations. During this study, typical office environment media were spiked at the 4-20microg/g level with either a complex munitions grade sample of tabun (GA) or with a standard containing the three nerve agents, sarin (GB), cyclohexyl methylphosphonofluoridate (GF), soman (GD) and the nerve agent simulant, triethyl phosphate (TEP), to evaluate the potentials of liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) and liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) for forensic purposes. An emerging technique, desorption electrospray ionization (DESI-MS/MS), was also investigated for the direct determination of TEP, GB and GD sampled onto solid phase microextraction (SPME) fibers exposed to spiked office media. The spiked chemical warfare agents were recovered with varying efficiencies during this study, but in all cases sufficient chemical warfare agent was recovered for mass spectrometric identification purposes. Full high resolution mass spectra were acquired for all the chemical warfare agents in the continuum mode, which typically resulted in mass measurement errors of 0.001Da or less.

Quantifying thumb opposition kinematics using dynamic computed tomography.

Current motion capture techniques all have shortcomings when applied to the 3D quantitative evaluation of thumb base motion. Dynamic CT might overcome these shortcomings but, so far, robustness of this technique in more than one specimen has not yet been demonstrated. The aim of the current study is to further evaluate the use of dynamic CT for quantification of thumb motion in a larger cadaveric study using a protocol which is feasible in a clinical context. A dynamic CT scan was acquired from six cadaveric human forearms, while a motion simulator imposed thumb opposition. After image acquisition and segmentation, carpal bone motion was quantified using helical axes. To enable comparisons between specimens, intersection points of the instantaneous helical axis with an anatomically defined plane were determined. Precision of the dynamic CT method, measured as variation in distances between silicon nitride beads between frames of a dynamic scan, was 0.43mm (+/-0.09mm) when fixed to the skin and 0.13mm (+/-0.04mm) when embedded into the bone. Absolute deviation between known and measured distances were not larger than 0.34mm. We could demonstrate and quantify that thumb opposition is associated with motion at the trapeziometacarpal and scaphotrapezotrapezoidal joints. High consistency in motion patterns between specimen were found, while the radiation dose was limited. We conclude that dynamic CT can be used to visualize and quantify 3D thumb kinematics, making it a promising method to explore kinematics in vivo.

Production of cytokines at the operation site.

BACKGROUND AND AIM: Cytokines are part of a family of molecules involved in the initiation, control and termination of the events that occurs in wound healing process. Aim of this study was to evaluate the production of some cytokines [interleukin (IL)-6, IL-10, IL-1alpha, IL-1ra, interferon (IFN)-gamma] in the drainage wound fluid from patients undergoing incisional hernia repair. METHODS: Ten female patients with abdominal midline incisional hernia undergoing to surgical repair were included in this study. In all cases a closed suction drain was placed in the wound below the fascia and it was removed on the 4th postoperative day. Wound fluid was collected on the 1st, 2nd, 3rd and 4th day and its amount in each time was recorded. The production of IL-6, IL-10, IL-1alpha, IL-1ra and IFN-gamma were evaluated as quantity produced in 24 hour. RESULTS: In all patients the amount of drain fluid from surgical wound was highest on the 1st day after surgery, afterwards there is a significant reduction. The production of all cytokines evaluated was highest on the 1st day decreasing on the 2nd day except for IL-1alpha that not show any modification. The produciton of IL-1ra, IL-6, IL-1alpha and IL-10 was significantly reduced on the 3rd and 4th postoperative day in comparison with the respectively values recorded on the 1st day, whereas IFN-gamma levels were similar. CONCLUSIONS: The dosage of cytokines in the drain fluid led us to better evaluated the events that follow surgical wound and their analysis offers further information in the role of cytokines in healing process, with the goal to get supportive treatments to promote the best evolution.

Promoter for the human ferritin heavy chain-encoding gene (FERH): structural and functional characterization.

We conducted a functional analysis of the promoter for the human ferritin heavy chain-encoding gene (pFERH) in HepG2 and HeLa cells. The activity of pFERH is equivalent in both cell types, despite their different ferritin (Fer) isotypes. Transfections of a series of 5'-deletion mutants indicate that pFERH activity is essentially dependent on two motifs. One of them, accounting for about 50% of the total transcriptional activity, is recognized by the RNA polymerase II transcription factor, Sp1, and the other by a low-affinity factor present in both the cell types analyzed.

PKC-dependent phosphorylation of the p97 repressor regulates the transcription of aldolase A L-type promoter.

Expression of mouse aldolase A L-type mRNA is negatively modulated by a cis element (AldA-NRE), located within the aldolase A distal promoter (pL). AldA-NRE interacts with a 97-kDa repressor protein (p97), which binds DNA in a cell cycle-dependent manner. We demonstrate that the binding between AldA-NRE and p97 decreases during differentiation of human Caco-2 cells and is inversely correlated with L-type mRNA expression. Phosphorylation of the p97 repressor weakened its DNA binding activity in differentiated Caco-2 cells, while dephosphorylation enhanced the binding in proliferating cells. Stimulation of protein kinase C (PKC) in vivo decreased the binding of p97 to AldA-NRE and stimulated transcription, while inhibition of PKC stimulated p97 binding and downregulated transcription. These findings suggest that PKC is a mediator of the binding and silencing function of the p97/AldA-NRE repressor complex.

Clinical findings in patients with SLE whose sera contain antibodies to ribosomal ribonucleoprotein.

In a clinical and serological study performed on a large series of patients with different connective tissue diseases, anti-ribosomal ribonucleoprotein (rRNP) antibodies were detected only in a small proportion of sera with systemic lupus erythematosus (SLE). SLE patients positive for anti-rRNP autoantibodies showed a significantly higher incidence of hemolytic anemia. The reasons for this surprising association are still unclear; however, this finding suggests that rRNP precipitin might be considered as a useful marker of a particular subgroup of patients with SLE.

Effect of partially modified retro-inverso analogues derived from C-reactive protein on the induction of nitric oxide synthesis in peritoneal macrophages.

1. The ability of three modified tetrapeptides, representing fragments of the C-reactive protein (CRP) sequence and stabilized in the first peptide bond by retro-inverso modification, to affect the secretion of nitric oxide (NO) was studied in macrophages of BALB/c mice. 2. These tetrapeptides, resembling the aminoacid sequence of tuftsin (CRP 1, H-gThr-(R,S)mLys-Pro-Leu-OH, ITF 1192; CRP II, H-gGly-(R, S)mLys-Pro-Arg-OH, ITF 1127; CRP III, H-gThr-(R,S)mLys-Pro-Gln-OH. ITF 1193), were able to induce NO synthesis by peritoneal macrophages in a dose-dependent manner; the most stimulating dose was 1000 ng ml-1 for CRP II and 100 ng ml-1 for CRP I and CRP III. NO synthesis was not strictly dependent on lipopolysaccharide (LPS) activation. 3. The enhanced effect of retro-inverso CRP-related analogues on the expression of iNOS (inducible NO synthase) was confirmed by higher levels of iNOS activity in the cytosol and by the increase in iNOS protein, as evaluated by Western blot analysis, in macrophages stimulated by CPR compared with untreated ones. 4. The production of NO by retro-inverso CRP-peptide analogues was significantly inhibited by dexamethasone (20 microM), NG-monomethyl-L-arginine (L-NMMA) (500 microM) and pyrrolidine dithiocarbamate (PDTC) (100 microM). 5. Retro-inverso CRP-peptide analogues stimulated macrophages to produce high levels of interleukin-1 (IL-1) and tumour necrosis factor-alpha (TNF-alpha) in the presence of LPS. 6. Retro-inverso CRP-peptide analogues stimulated NO synthesis by the enhancement of endogenously produced IL-1 and TNF-alpha, as the treatment of peritoneal macrophages with LPS in the presence of neutralizing anti-IL-1 and anti-TNF monoclonal antibodies (mAbs) reduced retro-inverso analogue-induced NO secretion. Data indicate a predominant role for IL-1 alpha in the induction of NO secretion by retro-inverso analogues. 7. These results suggest that retro-inverso CRP derived analogues act as costimulators of NO and cytokine synthesis in macrophages. The mechanisms by which they cause iNOS induction appear to be strongly dependent on the activation of nuclear factor-kappa B (NF-kappa B).

Effects of chemically modified tetracyclines (CMTs) in sensitive, multidrug resistant and apoptosis resistant leukaemia cell lines.

Recently discovered chemically modified tetracyclines (CMTs) have shown in vitro and in vivo anti-proliferative and anti-tumour activities. Here, we evaluated in vitro the anti-proliferative and apoptotic activity of six different dedimethylamino chemically modified tetracyclines (CMT-1, CMT-3, CMT-5, CMT-6, CMT-7 and CMT-8) in sensitive and multidrug resistant myeloid leukaemia cells (HL60 and HL60R) in vitro. Three of these compounds (CMT-5, CMT-6, CMT-7) showed low cytotoxic activity both in sensitive and in resistant cells, CMT-3 was endowed with a high anti-proliferative activity only in sensitive cells and was moderately effective as apoptosis inducing agent, with an activity similar to that shown by doxycycline. On the contrary, CMT-1 and CMT-8 were very effective as programmed cell death inducing agents. The apoptotic pathway activated by these compounds involved the activation of caspases, especially caspase-9 and, for CMT-1, also the activation of FAS: Interestingly CMT-8, but not CMT-1, was able to induce apoptosis in multidrug resistant HL60R and in Fas-ligand resistant HUT78B1 cell lines. These properties, together with others previously described (e.g. anti-metastatic and anti-osteolytic activities), suggest that CMT-8 may have important applications in the clinical management of cancer. The comparative analysis of structure-activity relationship of CMT-8 and doxycycline suggests that the C-5 hydroxy moiety may play an important role in conferring activity in multidrug resistant cells. These findings appear to support the hypothesis that CMT-8 may represent an interesting lead for the development of a new class of potent apoptosis inducer agents active in multidrug resistant and Fas-ligand resistant malignancies.

Tetracycline inhibits the nitric oxide synthase activity induced by endotoxin in cultured murine macrophages.

Here we investigate the effects of tetracycline base and of a semi-synthetic tetracycline derivative, doxycycline, on the induction of inducible nitric oxide synthase and, hence, on the production of nitric oxide (NO) by lipopolysaccharide in J774 macrophage cultured in vitro. The treatment of J774 line with tetracycline base (6.25-250 microM) or doxycycline (5-50 microM) dose-dependently decreased the lipopolysaccharide-stimulated (1 microg/ml) inducible NO synthase activity and, consequently, nitrite formation. For instance, the inhibition was 70% for tetracycline base at 250 microM and 68% for doxycycline at 50 microM. The inhibitory effect of tetracyclines was due neither to a reduction in the viability of the cells, studied as colorimetric 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay, nor to an indiscriminate inhibition of total protein synthesis, but to a specific decrease in inducible NO synthase protein content in the cells, as attested by the significant reduction of the expression of inducible NO synthase, assayed by sodium-dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot. However, no effect of tetracyclines on inducible NO synthase mRNA accumulation could be demonstrated in lipopolysaccharide-stimulated macrophage line, suggesting that the inhibitory effect of tetracyclines on NO synthesis involves post-transcriptional events. The reduction in lipopolysaccharide-stimulated nitrite accumulation produced by tetracyclines was significantly less when they were applied 6 h after lipopolysaccharide and absent 12 h after lipopolysaccharide, indicating that tetracyclines modify an early event in inducible NO synthase activation operating after mRNA transcription. The findings presented in this study indicate that the modulation of NO synthesis is another possible pathway by which tetracyclines may function as anti-inflammatory compounds.

Anti-inflammatory effects of chemically modified tetracyclines by the inhibition of nitric oxide and interleukin-12 synthesis in J774 cell line.

We investigated the effects of chemically modified tetracyclines (CMTs) on the production of nitric oxide (NO) and on the synthesis of some cytokines: tumour necrosis factor alpha (TNF-alpha), interleukin(IL)-10 and IL-12 in lipopolysaccharide (LPS)-treated J774 cell line. Furthermore, we studied the ability of these drugs to modify the viability in LPS-stimulated J774 macrophages. CMTs decreased, in a dose-dependent manner, inducible NO synthase (iNOS) activity and, consequently, nitrite formation in J774 cultures. The CMT-induced decrease in NO production is due to the inhibition of enzyme activity rather than to a direct effect on enzyme expression. The absence of the inhibition in mRNA accumulation indicates that the inhibiting activity is mainly post-transcriptional. CMTs were unable to modulate TNF-alpha and IL-10 synthesis and they were not effective in modifying the transcription of relative mRNA in J774 macrophages. On the contrary, IL-12 mRNA expression was significantly increased by CMT-1 and CMT-8 with LPS activation. Since IL-12 protein secretion was inhibited by CMTs, these compounds interfere in the blocking of post-transcriptional events. The studies on cell viability showed that various CMTs induced a dose-dependent decrease in J774 macrophage viability. The cytotoxic activity was present even though NO production was inhibited by CMTs. These compounds appear to be able to activate apoptosis in aNO-independent way. Altogether, these results indicate that CMTs can exert anti-inflammatory effects by inhibiting NO synthesis, and they are able to modify cell viability by exerting a strong apoptotic activity.

Analysis of bioactive peptides by liquid chromatography-high-resolution electrospray mass spectrometry.

LC-high-resolution electrospray ionization (ESI)-MS data for a number of bioactive peptides, including substance P and bradykinins were acquired over a wide mass range by scanning the magnetic sector and calibrating externally with polyethylene glycol standards. Multiply charged ions were observed and errors between observed and theoretical monoisotopic molecular masses were typically in the 5 to 30 ppm range for the peptides during LC-ESI-MS and ESI-MS operation with magnetic sector resolutions between 2500 and 6000 (10% valley definition). Under collisionally activated dissociation conditions bn- and yn-series sequence ions were generally observed, enabling amino acid sequencing and the differentiation of lysine from glutamine, two amino acids differing in residue mass by only 0.0364 u. Mass accuracy was evaluated during an international round robin analytical exercise where the molecular masses of five unknown peptides were to be accurately determined. Isotopic clusters for charge states of up to +6 were fully resolved, facilitating the rapid and unambiguous assignment of charge states and calculation of monoisotopic molecular masses. Errors between theoretical and observed monoisotopic molecular masses were in the 2 to 18 ppm range for the five unknown peptides.

Packed capillary liquid chromatography-electrospray mass spectrometry analysis of organophosphorus chemical warfare agents.

Packed capillary column liquid chromatography (LC)-electrospray mass spectrometry (ESI-MS) was used for the first time to detect and identify four common organophosphorus chemical warfare agents in aqueous samples. Aqueous samples containing the organophosphorus chemical warfare agents in the 0.01 to 0.1 mg/ml range were analyzed directly by packed capillary LC-ESI-MS with the chemical warfare agents and several minor related impurities being well resolved under acetonitrile-water gradient elution conditions. The ESI-MS data for isopropyl methylphosphonofluoridate (sarin or GB), O-ethyl N,N-dimethylphosphoramidocyanidate (tabun or GA), cyclohexyl methylphosphonofluoridate (GF) and pinacolyl methylphosphonofluoridate (soman or GD) were acquired with a sampling cone voltage setting that promoted collisionally activated dissociation, and resulted in the acquisition of informative mass spectra containing both molecular and product ion information. The developed method appears to be an attractive alternative to GC-MS for the analysis of aqueous samples containing organophosphorus chemical warfare agents and their hydrolysis products, since they may be analyzed directly without the need for additional sample handling.

Packed capillary liquid chromatography-electrospray ionization (tandem) mass spectrometry of mustard hydrolysis products in soil.

A packed capillary liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method was developed and applied to the identification of mustard hydrolysis products in aqueous extracts of soil. In the first application the LC-ESI-MS/MS method was used to identify thiodiglycol and nine longer chain diols in soil samples taken at different locations and depths from a former mustard storage site as part of an ongoing environmental assessment. Aqueous extracts of the soil samples were analysed by LC-ESI-MS/MS using a quadrupole/time-of-flight tandem mass spectrometer operating with a resolution of 9000. High resolution product mass spectra were acquired for thiodiglycol, the hydrolysis product of mustard and nine other sulfur containing diols, including five longer chain diols that could not be identified during prior LC-ESI-MS analyses. The high resolution LC-ESI-MS/MS method was also incorporated into an analytical approach designed to provide rapid chemical warfare agent identification in cases where the chemical and/or biological warfare agent content of a sample is unknown. A sample handling method involving aqueous extraction of the soil sample in biocontainment level 3 (BL-3), followed by autoclave sterilization of the aqueous extract was developed. Once sterilized, the container and aqueous extract can then be safely manipulated outside of BL-3 in the analytical laboratories and may be analysed for the presence or absence of chemical warfare agents, their hydrolysis products or related compounds by LC-ESI-MS/MS.

Determination of sarin, soman and their hydrolysis products in soil by packed capillary liquid chromatography-electrospray mass spectrometry.

An analytical method based on aqueous ultrasonic extraction and packed capillary liquid chromatography-electrospray mass spectrometry (LC-ESI-MS) analysis was developed and compared to an existing gas chromatography(GC)-MS based method for the determination of sarin, soman and their hydrolysis products in contaminated soil. Three soils, a red clay, a tan sandy clay and a brown sandy clay loam, were spiked with sarin and soman and their initial hydrolysis products, isopropyl methylphosphonic acid and pinacolyl methylphosphonic acid, at the 10 microg/g level to assess recovery efficiency. Recovery of sarin and soman from the aqueous soil extracts was comparable to the existing analytical method, with a significant improvement in recovery being demonstrated for the chemical warfare agent hydrolysis products. Sarin and soman were recovered in the 20-90% range from the three soil types with aqueous extraction, while the hydrolysis products of these chemical warfare agents were extracted with recoveries in excess of 80%. The developed soil extraction and analysis method appears to be an attractive alternative to the GC-MS based method, since aqueous extracts containing chemical warfare agent hydrolysis products may be analysed directly, eliminating the need for additional sample handling and derivatization steps.

Packed capillary liquid chromatography-electrospray mass spectrometry of snow contaminated with sarin.

Packed capillary liquid chromatography-electrospray mass spectrometry (LC-ESI-MS) was used for the analysis of a snow sample that was accidentally contaminated with an organophosphorus chemical warfare agent during the destruction of a chemical munition. Sarin, its hydrolysis products and a number of related compounds were identified on the basis of acquired LC-ESI-MS data. Full mass spectra were acquired for 14 compounds, with all exhibiting MH+, [MH+ACN]+ ions and/or protonated dimers that could be used to confirm molecular mass. Sampling cone voltages from 20 to 70 V were utilized with the higher sampling voltages enhancing formation of structurally important product ions in the ESI interface. All data were acquired with a time-of-flight mass spectrometer with a resolution of 5,000 (50% valley definition), a resolution that aided in the assignment of elemental composition of the observed ions. The application of LC-ESI-MS to snow analysis appears to be an attractive alternative to the GC-MS methods, since both chemical warfare agents and their hydrolysis products may be analysed directly, eliminating the need for additional sample handling and derivatization steps.

Analysis of O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and its degradation products by packed capillary liquid chromatography-electrospray mass spectrometry.

Packed capillary column liquid chromatography (LC)-electrospray mass spectrometry (ESI-MS) was used for the first time to detect and identify O-ethyl, S-[2-(diisopropylamino)ethyl] methylphosphonothiolate (VX) and its degradation products, including compounds containing a P-CH3 bond, bis(diisopropylamino)thioalkanes and ureas commonly employed as VX stabilizers. The reported ESI-MS data were generally acquired with a higher sampling cone voltage, a setting that promoted collisionally activated dissociation, and resulted in the acquisition in informative mass spectra containing both molecular and product ion information. The developed method appears to be an attractive alternative to GC-MS for the analysis of aqueous sample containing the degradation products of VX, since they may be analysed directly with little risk of thermal decomposition and without the need for additional sample handling or derivatization. Application of this method to a degraded VX sample resulted in the detection of a number of novel polar and higher-molecular-mass degradation products, not previously associated with VX during GC-MS analysis.

Autoantibody to proliferating cell nuclear antigen (PCNA) in SLE: a clinical and serological study.

In a clinical and serological follow-up study on a large series of subjects with different connective tissue disorders, anti-PCNA/cyclin autoantibodies were found in about 3% of patients with SLE. Positive subjects showed a higher incidence of diffuse proliferative glomerulonephritis and hematological disorders than the general SLE population. A highly significant serological association between PCNA and SL/Ki autoantibodies (p less than 0.001) has been observed. Persistence or disappearance of serum PCNA antibodies were independent of any clinical and serological feature or the therapeutic regimen employed.