Semiautomated Middle Ear Volume Measurement as a Predictor of Postsurgical Outcomes for Congenital Aural Atresia.

BACKGROUND AND PURPOSE: Middle ear space is one of the most important components of the Jahrsdoerfer grading system (J-score), which is used to determine surgical candidacy for congenital aural atresia. The purpose of this study was to introduce a semiautomated method for measuring middle ear volume and determine whether middle ear volume, either alone or in combination with the J-score, can be used to predict early postoperative audiometric outcomes. MATERIALS AND METHODS: A retrospective analysis was conducted of 18 patients who underwent an operation for unilateral congenital aural atresia at our institution. Using the Livewire Segmentation tool in the Carestream Vue PACS, we segmented middle ear volumes using a semiautomated method for all atretic and contralateral normal ears on preoperative high-resolution CT imaging. Postsurgical audiometric outcome data were then analyzed in the context of these middle ear volumes. RESULTS: Atretic middle ear volumes were significantly smaller than those in contralateral normal ears (P < .001). Patients with atretic middle ear volumes of >305 mm3 had significantly better postoperative pure tone average and speech reception thresholds than those with atretic ears below this threshold volume (P = .01 and P = .006, respectively). Atretic middle ear volume incorporated into the J-score offered the best association with normal postoperative hearing (speech reception threshold ≤ 30 dB; OR = 37.8, P = .01). CONCLUSIONS: Middle ear volume, calculated in a semiautomated fashion, is predictive of postsurgical audiometric outcomes, both independently and in combination with the conventional J-score.

Is there a benefit to use calculated percent body fat or age- and gender-adjusted BMI-SDS(LMS) to predict risk factors for cardiovascular disease? A German/Austrian multicenter DPV-Wiss analysis on 42 048 type 2 diabetic patients.

OBJECTIVE: In clinical practice Body Mass Index is generally used to evaluate overweight status in adults. The present multicenter study examines whether Body Mass Index (BMI), age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculated %body fat is a better predictor for cardiovascular disease risk factors, specifically hypertension and dyslipidemia, in a high-risk population. METHODS: Data of 42 048 adult type 2 diabetic patients (median age: 67.1 years) from 161 centers in Germany (n=158) and Austria (n=3) registered in a standardized, prospective, computer-based documentation program, were included in the study. For each patient body weight, height, blood pressure and blood lipids were documented. Spearman correlation analyses as well as multivariable logistic regression models were used to examine the relationship between anthropometric measurements and cardiovascular disease risk factors. RESULTS: Correlation and regression analyses revealed minor, non significant differences between the 3 anthropometric measurements (all p>0.05). In both genders, relationships between anthropometric measurements and hypertension or reduced HDL-cholesterol were nearly identical. Only for increased triglycerides, the relations with the 3 anthropometric measurements were significantly stronger in males than in females (p<0.0001, respectively). With increasing age, associations between anthropometric measurements and hypertension, reduced HDL-cholesterol or increased triglycerides became weaker. Spearman correlation coefficients for total cholesterol and LDL-cholesterol revealed weak associations with the 3 anthropometric measurements. CONCLUSION: Compared to Body Mass Index, age- and gender-adjusted Body Mass Index Standard Deviation Score, or calculation of %body fat, has no further benefit to predict cardiovascular disease risk factors in adult type 2 diabetic patients.

Regulation of cAMP-responsive element-binding protein-mediated transcription by the SNF2/SWI-related protein, SRCAP.

SRCAP (SNF2-related CPB activator protein) belongs to the SNF2 family of proteins whose members participate in various aspects of transcriptional regulation, including chromatin remodeling. It was identified by its ability to bind to cAMP-responsive-binding protein (CREB)-binding protein (CBP), and it increases the transactivation function of CBP. The phosphoenolpyruvate carboxykinase (PEPCK) promoter was used as a model system to explore the role of SRCAP in the regulation of transcription mediated by factors that utilize CBP as a coactivator. We show that transcription of a PEPCK chloramphenicol acetyltransferase (CAT) reporter gene activated by protein kinase A (PKA) is enhanced 7-fold by SRCAP. In the absence of PKA this SRCAP-mediated enhancement does not occur, suggesting that SRCAP functions as a coactivator for PKA-activated factors such as CREB. Replacing the PEPCK promoter binding site for CREB with a binding site for Gal4 (DeltaCRE (cAMP-responsive element) Gal4 PEPCK-CAT reporter gene) blocks the ability of SRCAP to activate transcription despite the presence of PKA. Expression of a Gal-CREB chimera restores the ability of PKA to regulate transcription of the DeltaCRE Gal4 PEPCK gene and restored the ability of SRCAP to stimulate PKA-activated transcription. In addition, SRCAP in the presence of PKA enhances the ability of the Gal-CREB chimera to activate transcription of a Gal-CAT reporter gene that contains only binding sites for Gal4. SRCAP binds to CBP amino acids 280-460, a region that is important for CBP to function as a coactivator for CREB. Overexpression of a SRCAP peptide corresponding to this CBP binding domain acts as a dominant negative inhibitor of CREB-mediated transcription. Structure-function studies were done to explore the mechanism(s) by which SRCAP regulates transcription. These studies indicate that the N-terminal region of SRCAP, which contains five of the seven regions that comprise the ATPase domain, is not needed for activation of CREB-mediated transcription. SRCAP apparently has several domains that participate in the activation of transcription.

[Speech development and intelligence in autism. How uniform is Asperger syndrome?]. / Sprachentwicklung und Intelligenzniveau beim Autismus. Wie eigenständig ist das Asperger-Syndrom?

Since the introduction of a separate diagnosis for Asperger's syndrome in the ICD-10 and DSM-IV classification systems, a controversial debate has continued on whether Asperger's syndrome is a specific, clearly distinguishable disorder within the autistic spectrum or whether it represents a milder phenotypical variation of autism. The effect on the amount of autistic symptoms of the variables language delay and level of intelligence was analyzed within a sample of individuals exhibiting autism diagnosed by standardized methods. Both variables showed a significant effect on the degree of autistic symptoms in that impairments in social interaction were less noticeable. In addition, a subsample of individuals exhibited symptoms assumed to be characteristic for Asperger's syndrome. The findings support the assumption that autism and Asperger's syndrome represent "extreme points" on a scale of severity, which leads to the suggestion that the classification of different subtypes of autism could be abandoned in favor of a dimensional (multiaxial) approach.

Multiacreage evaluation of aerially applied adherent malathion granules for selective insect control and indirect reduction of mycotoxigenic fungi in specialty corn.

Aerially applied adherent corn flour granules containing 1% malathion were more often as, or more, effective than 15% chlorpyrifos (Lorsban 15G) granules in controlling caterpillars and sap beetles in high amylose corn in 1997 than 1996. Use of malathion granules corresponding closely in size to chlorpyrifos granules in the second year of the study apparently increased relative efficacy. Significantly less corn borer damage occurred on plants (1996) or ears (1997) within 2 wk of application for both types of insecticide granules compared with untreated plots. In 1997, there were sixfold fewer milk stage ears with more than 20 kernels damaged per ear in the malathion-treated plots compared with chlorpyrifos-treated plots, and severity of caterpillar damage was also less in malathion versus chlorpyrifos-treated plots at harvest. Control of beetles (corn rootworm adults and sap beetles) for both treatments was less effective compared with caterpillars. Significant corn rootworm adult control was noted for both chlorpyrifos and malathion in 1996 and significant sap beetle control was noted for the malathion granules in 1997. Significantly fewer live lady beetles, and more dead lady beetles were present in chlorpyrifos-treated plots compared with malathion-treated or untreated plots in 1996. The incidence and severity of Fusarium mold on ears at harvest was often indirectly reduced by both malathion treatments and chlorpyrifos treatments, with the malathion treatment significantly better than the chlorpyrifos treatment in one case.

Multiple conserved segments of E1 small nucleolar RNA are involved in the formation of a ribonucleoprotein particle in frog oocytes.

E1/U17 small nucleolar RNA (snoRNA) is a box H/ACA snoRNA. To identify E1 RNA elements required for its assembly into a ribonucleoprotein (RNP) particle, we have made substitution mutations in evolutionarily conserved sequences and structures of frog E1 RNA. After E1 RNA was injected into the nucleus of frog oocytes, assembly of this exogenous RNA into an RNP was monitored by non-denaturing gel electrophoresis. Unexpectedly, nucleotide substitutions in many phylogenetically conserved segments of E1 RNA produced RNPs with abnormal gel-electrophoresis patterns. These RNA segments were at least nine conserved sequences and an apparently conserved structure. In another region needed for RNP formation, the requirement may be sequence(s) and/or structure. Base substitutions in each of these and in one additional conserved E1 RNA segment reduced the stability of this snoRNA in frog oocytes. Nucleolar localization was assayed by fluorescence microscopy after injection of fluorescein-labelled RNA. The H box (ANANNA) and the ACA box are both needed for efficient nucleolar localization of frog E1 RNA.

Characterization of Escherichia coli isolated from healthy dogs.

Five month old dogs from a Midwestern research kennel occasionally developed bloody diarrhea after shipment to other facilities. As previous diagnostic efforts failed to reveal any potential pathogens in feces from normal and diarrheic dogs, Escherichia coli was investigated for select virulence properties that may contribute to the occurrence of bloody diarrhea. Fecal swabs from 52 healthy dogs were examined for E. coli. Two hundred and sixty E. coli-like colonies were screened by PCR for the attaching and effacing (eae) gene, Shiga toxin (stx) genes, and the heat-stable enterotoxin type A (sta) gene. One hundred forty two of the 260 E. coli-like colonies (54.6%) from 43 dogs were eae or sta positive; and 60 of the eae and/or sta positive isolates were examined further. Among the 60 isolates, 23 (38.3%) possessed the eae gene, 32 (53.3%) possessed the sta gene, and five (8.3%) possessed both eae and sta genes (eae+/sta+). Of the 60 isolates, six sta+ and one eae+/sta+ isolates were hemolytic. When examined in the suckling mouse assay, five of six sta+ isolates and three of four eae+/sta+ isolates gave gut-to-remaining carcass ratios > or =0.083, indicating expression of heat-stable enterotoxin. These enterotoxin-producing isolates belonged to serogroups O42, O170, and O-negative.

Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection.

Human immunodeficiency virus type 1 (HIV-1)-specific immune responses over the course of rapidly progressive infection are not well defined. Detailed longitudinal analyses of neutralizing antibodies, lymphocyte proliferation, in vivo-activated and memory cytotoxic T-lymphocyte (CTL) responses, and viral sequence variation were performed on a patient who presented with acute HIV-1 infection, developed an AIDS-defining illness 13 months later, and died 45 months after presentation. Neutralizing-antibody responses remained weak throughout, and no HIV-1-specific lymphocyte proliferative responses were seen even early in the disease course. Strong in vivo-activated CTL directed against Env and Pol epitopes were present at the time of the initial drop in viremia but were quickly lost. Memory CTL against Env and Pol epitopes were detected throughout the course of infection; however, these CTL were not activated in vivo. Despite an initially narrow CTL response, new epitopes were not targeted as the disease progressed. Viral sequencing showed the emergence of variants within the two targeted CTL epitopes; however, viral variants within the immunodominant Env epitope were well recognized by CTL, and there was no evidence of viral escape from immune system detection within this epitope. These data demonstrate a narrowly directed, static CTL response in a patient with rapidly progressive disease. We also show that disease progression can occur in the presence of persistent memory CTL recognition of autologous epitopes and in the absence of detectable escape from CTL responses, consistent with an in vivo defect in activation of CTL.

Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: the ariel project for the prevention of transmission of HIV from mother to infant.

Host immunologic factors, including human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL), are thought to contribute to the control of HIV type 1 (HIV-1) replication and thus delay disease progression in infected individuals. Host immunologic factors are also likely to influence perinatal transmission of HIV-1 from infected mother to infant. In this study, the potential role of CTL in modulating HIV-1 transmission from mother to infant was examined in 11 HIV-1-infected mothers, 3 of whom transmitted virus to their offspring. Frequencies of HIV-1-specific human leukocyte antigen class I-restricted CTL responses and viral epitope amino acid sequence variation were determined in the mothers and their infected infants. Maternal HIV-1-specific CTL clones were derived from each of the HIV-1-infected pregnant women. Amino acid substitutions within the targeted CTL epitopes were more frequently identified in transmitting mothers than in nontransmitting mothers, and immune escape from CTL recognition was detected in all three transmitting mothers but in only one of eight nontransmitting mothers. The majority of viral sequences obtained from the HIV-1-infected infant blood samples were susceptible to maternal CTL. These findings demonstrate that epitope amino acid sequence variation and escape from CTL recognition occur more frequently in mothers that transmit HIV-1 to their infants than in those who do not. However, the transmitted virus can be a CTL susceptible form, suggesting inadequate in vivo immune control.

Molecular genetic analysis of the FMR-1 gene in a large collection of autistic patients.

A genetic etiology in autism is now strongly supported by family and twin studies. A 3:1 ratio of affected males to females suggests the involvement of at least one X-linked locus in the disease. Several reports have indicated an association of the fragile X chromosomal anomaly at Xq27.3 (FRAXA) with autism, whereas others have not supported this finding. We have so far collected blood from 105 simplex and 18 multiplex families and have assessed 141 patients by using the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observation Scale, and psychometric tests. All four ADI-R algorithm criteria were met by 131 patients (93%), whereas 10 patients (7%) showed a broader phenotype of autism. Southern blot analysis was performed with three different enzymes, and filters were hybridized to an FMR-1-specific probe to detect amplification of the CCG repeat at FRAXA, to the complete FMR-1 cDNA probe, and to additional probes from the neighborhood of the gene. No significant changes were found in 139 patients (99%) from 122 families, other than the normal variations in the population. In the case of one multiplex family with three children showing no dysmorphic features of the fragile X syndrome (one male meeting 3 out of 4 ADI-algorithm criteria, one normal male with slight learning disability but negative ADI-R testing, and one fully autistic female), the FRAXA full-mutation-specific CCG-repeat expansion in the genotype was not correlated with the autism phenotype. Further analysis revealed a mosaic pattern of methylation at the FMR-1 gene locus in the two sons of the family, indicating at least a partly functional gene. Therefore, we conclude that the association of autism with fragile X at Xq27.3 is non-existent and exclude this location as a candidate gene region for autism.

Degenerate and promiscuous recognition by CTL of peptides presented by the MHC class I A3-like superfamily: implications for vaccine development.

Recent data demonstrate that HLA class I alleles can be grouped into superfamilies based on similarities of their peptide-binding motifs. In this study, we have tested the immunogenicity and antigenicity of peptides capable of degenerate binding to multiple HLA class I molecules of the A3-like superfamily. The assay systems utilized included both primary in vitro cultures of lymphocytes from healthy donors, as well as in vitro restimulation of lymphocytes from HIV-infected individuals. Several of the peptides capable of binding more than one HLA A3-like class I molecule were also found to be immunogenic in the context of this same group of A3-like molecules (degenerate CTL recognition). Furthermore, some of the CTL lines thus generated demonstrated promiscuous recognition of the cognate epitope in the context of MHC molecules from more than one member of the superfamily. The fine Ag specificity of this phenomenon was further analyzed using two promiscuous CTL clones derived from A3 and A11 individuals, respectively, and specific for an epitope in the HIV-1 reverse transcriptase. By the use of single-amino acid-substitution analogues, it was demonstrated that the fine specificity of the TCR is largely maintained between MHC-matched and MHC-mismatched presentation of peptide within the A3-like superfamily. These results indicate that the similar peptide-binding specificities among different members of the A3-like superfamily can be reflected in a remarkable similarity in the peptide-MHC complex structures engaged by the TCR and responsible for T cell activation.

Cytotoxicity of solid lipid nanoparticles as a function of the lipid matrix and the surfactant.

PURPOSE: Assessment of the in vitro cytotoxicity of solid lipid nanoparticles (SLNs) as a function of lipid matrix (Dynasan 114, Compritol ATO 888), and stabilizing surfactant (poloxamers, Tween 80, soya lecithin, and sodium dodecyl sulphate). Comparison with other colloidal carriers should determine their potential use in the clinic. METHODS: SLNs were produced by high pressure homogenisation. Cytotoxicity was assessed by measuring the viability of HL60 cells and human granulocytes after incubation with SLNs. Particle internalisation was quantified by chemiluminescence measurements. RESULTS: The nature of the lipid had no effect on viability; distinct differences were found for the surfactants. Binding to the SLN surface reduced markedly the cytotoxic effect of the surfactants, e.g., up to a factor of 65 for poloxamer 184. The permanent HL60 cell line-differentiated from cells with granulocyte characteristics by retinoic acid treatment-yielded results identical to freshly isolated human granulocytes. In general, the SLNs showed a lower cytotoxicity compared to polyalkylcyanoacrylate and polylactic/glycolic acid (PLA/ GA) nanoparticles. CONCLUSIONS: Because the results are identical when using human granulocytes, differentiated HL60 cells can be used as an easily accessible in vitro test system for i.v. injectable SLN formulations. The SLNs appear suitable as a drug carrier system for potential intravenous use due to their very low cytotoxicity in vitro.

Overlapping epitopes in human immunodeficiency virus type 1 gp120 presented by HLA A, B, and C molecules: effects of viral variation on cytotoxic T-lymphocyte recognition.

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) are thought to exert immunologic selection pressure in infected persons, yet few data regarding the effects of this constraint on viral sequence variation in vivo, particularly in the highly variable Env protein, are available. In this study, CD8+ HIV type 1 (HIV-1) envelope-specific CTL clones specific for gp120 were isolated from peripheral blood mononuclear cells of four HIV-infected individuals, all of which recognized the same 25-amino-acid (aa) peptide (aa 371 to 395), which is partially contained in the CD4-binding domain of HIV-1 gp120. Fine mapping studies revealed that two of the clones optimally recognized the 9-aa sequence 375 to 383 (SFNCGGEFF), while the two other clones optimally recognized the epitope contained in the overlapping 9-aa sequence 376 to 384 (FNCGGEFFY). Lysis of target cells by the two clones recognizing aa 375 to 383 was restricted by HLA B15 and Cw4, respectively, whereas both clones recognizing aa 376 to 384 were restricted by HLA A29. Sequence variation, relative to the IIIB strain sequence used to identify CTL clones, was observed in autologous viruses in the epitope-containing region in all four subjects. However, poorly recognized autologous sequence variants were predominantly seen for the A29-restricted clones, whereas the clones specific for SFNCGGEFF continued to recognize the predominant autologous sequences. These results suggest that the HLA profile of an individual may not only be important in determining the specificity of CTL recognition but may also affect the ability to recognize virus variants and suppress escape from CTL recognition. These results also identify overlapping viral CTL epitopes which can be presented by HLA A, B, and C molecules.

Influence of fluorescent labelling of polystyrene particles on phagocytic uptake, surface hydrophobicity, and plasma protein adsorption.

PURPOSE: To investigate the influence of fluorescent labelling of polystyrene particles on phagocytic uptake, surface hydrophobicity and protein adsorption. METHODS: Phagocytic uptake was analysed using chemiluminescence. Hydrophobicity was quantified by adsorption measurements of a hydrophobic dye. Protein adsorption was evaluated by two-dimensional electrophoresis. RESULTS: Commercially available fluorescently labelled particles showed marked differences when compared to unlabelled particles: phagocytic uptake and surface hydrophobicity of labelled particles were diminished. Also the plasma protein adsorption pattern was found to be different from the unlabelled particles: for example, the amount of fibrinogen adsorbed was strongly reduced on the labelled particles. On the other hand, some unknown proteins could be detected on the fluorescently marked particles. In contrast, plain polystyrene particles and labelled ones could be successfully synthesised by Paulke which did not show any considerable differences in phagocytic uptake, surface hydrophobicity and protein adsorption. Polysorbate 20 added as stabilizer to particle suspensions led to completely different behaviour of the particles: the particles showed altered protein adsorption patterns, dominated by immunoglobulins and especially by apolipoproteins. Furthermore, these particles were not phagocytized at all. CONCLUSIONS: Surface hydrophobicity and phagocytic uptake in vitro as well as the interactions with plasma proteins of commercially available polystyrene particles were strongly affected by fluorescent labelling. Particles synthesised by Paulke remained unchanged after labelling. The results show the importance of thorough surface characterization for using particles in test systems in vitro and in vivo.

Gradient liquid chromatographic method for determination of chlorhexidine and its degradation products in bulk material.

A liquid chromatographic method was developed for determination of chlorhexidine and its degradation products in unformulated drug substance. A nonlinear gradient from 80% 0.1M ammonium acetate buffer, pH 5.0, to 20% buffer over 90 min (balance is acetonitrile) is applied to a 3 microns octadecylsilane bonded-phase column. The drug and some of its degradation products are determined at 230 nm. Of 11 previously identified degradation products, 9 are determined with good precision (relative standard deviation of peak area is < 2%).

The standardized diagnosis of autism, Autism Diagnostic Interview-Revised: interrater reliability of the German form of the interview.

The feasibility and reliability of the German form of the revised parental interview to diagnose autism (Autism Diagnostic Interview-Revised, ADI-R) was investigated in this study. Brief examples of the description of formerly and currently used diagnostic guidelines are given and the outline of the interview algorithm which establishes thresholds for inclusion criteria. An excellent-to-good reliability could be demonstrated for the main symptoms according to the classification rules of the ICD-10 and DSM-IV for a sample of autistic subjects at different ages and intellectual levels. The results approve the use of this interview for research and clinical purposes.

[The intelligence structure of autistic persons]. / Untersuchungen zur Intelligenzstruktur autistischer Personen.

In a research project on the genetics of autistic disorders 115 subjects were examined. An autistic disorder was diagnosed in 102 of the subjects using the standardized Autism Diagnostic Interview (ADI; Le Couteur et al., 1989/ADI-R; Lord et al., 1994). The WAIS-R or WISC-R could be administered to 42 of the subjects. The mean full-scale IQ was 84.4, slightly below the range of normal intelligence. The mean verbal IQ (89.3) was considerably higher than the performance IQ (78.9). Analysis of the subtest patterns showed the highest scores to be in those subtests measuring knowledge of dates and facts and visuospatial abilities. The lowest scores were on subtests requiring an understanding of social relations and the ability to understand concrete social actions. This subtest pattern confirms results of other studies on the intelligence of individuals with autism and was independent of gender and level of intelligence. The subtest pattern appears to be specific for autistic disorder; it has been interpreted with reference to the theory of "weak central coherence" (Frith, 1989; Shah & Frith, 1993), which postulates that in autistic individuals stimulus perception and processing occurs independently of the general context. The results suggest that the differentiation between different types of autistic disorders should be abandoned in favor of a continuum of autistic disorders with differing degrees of severity.

Effect of interleukin-1-beta and tumor necrosis factor-alpha on cartilage proteoglycan metabolism in vitro.

The activities of recombinant interleukin-1-beta (IL-1) and recombinant tumor necrosis factor-alpha (TNF) on cartilage proteoglycan metabolism were compared in an organ culture system. IL-1, 1 to 100 ng/ml, and TNF, 10 to 1,000 ng/ml, increased proteoglycan degradation. The concentration-response curves were parallel. The timecourse for degradation was similar for the two cytokines during a 6 day incubation. Both cytokines inhibited the synthesis of new proteoglycan as measured by 35S incorporation. The inhibition curves were parallel and concentration-related between 1 and 10 ng/ml for IL-1 and between 10 and 100 ng/ml for TNF. Maximal inhibition was 60% in the presence of IL-1 (10 ng/ml) or TNF (100 ng/ml), and plateaued at higher concentrations. IL-1 was ten fold more potent than TNF in stimulating proteoglycan breakdown and inhibiting proteoglycan synthesis. Degradation in response to TNF, but not to IL-1, could be blocked by a polyclonal antibody to TNF. A polyclonal antibody to IL-1 could block proteoglycan breakdown in response to both cytokines suggesting that TNF may be mediating proteoglycan degradation by inducing the production of interleukin-1.

In vivo studies on the effects of human recombinant interleukin-1 beta on articular cartilage.

Interleukin-1 (IL-1) is a cytokine produced by a number of connective-tissue and inflammatory cells which has been shown in organ culture to stimulate the breakdown of cartilage proteoglycans and inhibit their synthesis. Intraarticular injection of human recombinant IL-1 beta into the knee joints of rabbits induced a dose-related decrease in cartilage proteoglycan content and increased infiltration of cells into the synovial fluid. Following a single intraarticular injection, the loss of proteoglycan was maximal at 3 days. By 7 days, proteoglycan content began to return toward control levels. IL-1 also resulted in a dose-related decrease in the ability of cartilage to synthesize new proteoglycan as measured by 35S incorporation. These in vivo effects of IL-1 on articular cartilage closely reflect those effects observed in vitro in organ culture and are consistent with the hypothesis that IL-1 may play a role as a mediator of the loss of cartilage in some arthritic diseases.