Expression of Phosphorylated KIT in Canine Mast Cell Tumor.

Canine cutaneous mast cell tumor (MCT) is the most common canine skin tumor and exhibits variable biologic behavior. Signaling through the KIT receptor tyrosine kinase promotes cellular proliferation and survival and has been shown to play a role in MCT progression. Despite investigations into numerous biomarkers and the proposal of several grading schemas, no single marker or grading system can accurately predict outcome in canine MCT. The first aim of this study was to develop an immunohistochemical assay to measure phosphorylated KIT (pKIT) to investigate its association with 2 commonly used grading systems and other established prognostic markers for canine MCT. Thirty-four archived MCTs were evaluated for expression of pKIT and Ki-67, KIT localization, mitotic count, mutations in exons 8 and 11 in c-kit, and grading by the Patnaik and 2-tier systems. Expression of pKIT was significantly ( P < .05) correlated with the 2-tier grading scheme and c-kit mutation. Correlation approached significance ( P = .06) with Mitotic Index (MI) and Ki-67. An additional aim was to determine whether pKIT labeling provides a pharmacodynamic marker for predicting response to the receptor tyrosine kinase inhibitor toceranib (TOC). MCTs from 4 of 7 patients demonstrated a partial response to TOC. pKIT expression was assessed by immunohistochemistry in biopsies obtained before and 6 hours after the patients were treated with TOC. Reduced pKIT expression after TOC treatment was demonstrated in 3 of the 4 patients with a partial response compared to 1 of the 3 nonresponders. Collectively, these results demonstrate that immunohistochemical detection of pKIT may be a clinically relevant assay to evaluate the activation status of the major oncogenic pathway in canine MCT.

Approximate testing in two-stage nonlinear mixed models.

We investigate here small sample properties of approximate F-tests about fixed effects parameters in nonlinear mixed models. For estimation of population fixed effects parameters as well as variance components, we apply the two-stage approach. This method is useful and popular when the number of observations per sampling unit is large enough. The approximate F-test is constructed based on large sample approximation to the distribution of nonlinear least squares estimates of subject-specific parameters. We recommend a modified test statistic that takes into consideration approximation to the large sample Fisher information matrix (See [1]). Our main focus is on comparing finite sample properties of broadly used approximate tests (Wald test and likelihood ratio test) and the modified F-test under the null hypothesis, especially accuracy of p-values (See [2]). For that purpose two extensive simulation studies are conducted based on pharmacokinetic models (See [3, 4]).

Prospective comparison of prostatic aspirate culture and cystocentesis urine culture for detection of bacterial infection in dogs with prostatic neoplasia.

OBJECTIVE: The purpose of this study was to determine whether prostatic aspirate culture is a superior method to detect infection compared to culture of urine collected by cystocentesis in dogs with prostatic neoplasia. MATERIALS AND METHODS: A prospective study was conducted and dogs with suspected or confirmed prostatic neoplasia were enrolled. Urinalysis was done and culture and antimicrobial susceptibility testing was performed on paired urine and prostatic aspirate samples collected at a single timepoint. RESULTS: Ten dogs with prostatic neoplasia were enrolled. All dogs had one or more clinical sign consistent with lower urinary tract disease. One dog (10%) had a positive urine culture, but negative prostatic aspirate culture, one dog (10%) had a positive prostatic aspirate culture, but negative urine culture, and one dog (10%) had both positive urine and prostatic aspirate cultures. Using prostatic aspirate culture as the reference standard, urine culture had a sensitivity for detecting infection of 87.5% (95% confidence interval 52.9 to 99.4) and specificity of 50% (92.6 to 97.4) in this population of dogs. CLINICAL SIGNIFICANCE: Positive cultures were uncommon with both culture collection methods. Study results did not identify prostatic aspirate culture to be a more sensitive method of detecting prostatic infection than urine culture collected by cystocentesis in these dogs with prostatic neoplasia.

Diagenesis of US Gulf Coast shales.

The burial diagenesis of mudstones is of major interest in petroleum geology1-3. Key questions which remain incompletely answered include the relative importance of temperature, time, changes in pore-water chemistry and organic maturation as driving mechanisms, and the relationship between diagenesis in mudstones and neighbouring sandstones4-7. We reconsider here the nature and timing of diagenesis in Gulf Coast Tertiary mudstones using data obtained by backscattered electron microscopy (BSEM) and energy-dispersive X-ray analysis (EDS) of cuttings from two Texas wells. Our observations confirm the mineralogical trends with depth reported by Hower et al.1 and suggest new evidence concerning the timing and causes of the changes. The most important mineralogical changes occurred in the zone of organic matter decarboxylation (zone IV8). We show that the sequence of burial diagenetic events can be established quickly and reliably by BSEM examination of shale cuttings, and demonstrate the use of foram tests and their authigenic mineral infillings as indicators of diagenesis in soft, fine-grained shales.

Decreased ratio of CD8+ T cells to regulatory T cells associated with decreased survival in dogs with osteosarcoma.

BACKGROUND: Increased numbers of regulatory T cells (Treg) and decreased ratios of CD8+ T cells to Treg have been shown to correlate with decreased survival times (ST) in humans with certain malignancies. A possible connection between Treg and ST in dogs with cancer has not been investigated previously. HYPOTHESIS: The purpose of this study was to compare numbers of Treg and T lymphocyte subsets in dogs with osteosarcoma (OSA) to those of healthy dogs and to determine whether pretreatment values were associated with disease-free interval or with ST. We hypothesized that Treg numbers would be increased in dogs with cancer and that dogs with a high percentage of Treg would have a poorer prognosis. ANIMALS: Twelve client-owned dogs with appendicular OSA were entered into a prospective clinical trial. Twenty-two healthy dogs were used as controls. METHODS: The percentages and numbers of Treg and CD4+ and CD8+ T cells in blood, lymph nodes, and tumors were determined with flow cytometry and compared between dogs with OSA and control dogs. RESULTS: Dogs with OSA had significantly fewer circulating CD8+ T cells and significantly more Treg compared with healthy dogs. The CD8/Treg ratio also was significantly lower in dogs with OSA compared with control dogs. In dogs with OSA, a decreased CD8/Treg ratio was associated with significantly shorter STs. CONCLUSIONS: These data support a role for Treg in the immune control of canine OSA and suggest that determination of the CD8/Treg ratio may be useful for assessing outcomes.

Rehabilitation and transition after lung transplantation in children.

We describe the key components of an outpatient pediatric recovery and rehabilitation program set up within the adult lung transplant service at the Alfred Hospital, Melbourne. Following discharge, pediatric lung transplant recipients and their families participated in an intensive 3-month outpatient rehabilitation program. Weekly sessions included education regarding transplant issues, physiotherapy, and occupational therapy sessions. The overall aim of the program was to comprehensively address physical rehabilitation and psychosocial and educational needs. Sessions tailored to meet the individual needs of the child were presented at an appropriate cognitive level. Education sessions for both the children and parents focused on medications, identification of infection and rejection, nutrition, physiotherapy/rehabilitation, occupational roles and stress management, donor issues, psychosocial readjustment, and transition issues. Physiotherapy included a progressive aerobic and strength training program, postural reeducation, and core stability. We incorporate Age-appropriate play activities: running, dancing, jumping, ball skills, and so on. Occupational therapy sessions addressed the primary roles of patient, students, and player. Transitions such as returning to school, friends, and the community were explored. Issues discussed included adjustment to new health status, strategies to manage side effects of medications, and altered body image issues. Weekly multidisciplinary team meetings were used to discuss and plan the rehabilitation progress. School liaison and visits occurred prior to school commencement with follow-up offered to review the ongoing transition process. Both patients and parents have reported a high level of satisfaction with the rehabilitation program. We plan to formally evaluate the program in the future.

Patient characteristics, prognostic factors and outcome of dogs with high-grade primary mediastinal lymphoma.

The goals of this retrospective study were to determine the patient characteristics of dogs with high-grade primary mediastinal lymphoma and to determine outcome and associated prognostic factors. A total of 42 dogs were identified, in which 36 received treatment and had follow-up information available. The most common clinical signs included lethargy, anorexia and polyuria/polydipsia. Hypercalcemia and pleural effusion were common findings at diagnosis. The phenotype was almost exclusively T-cell, most often in association with lymphoblastic cytomorphology as defined by the World Health Organization (WHO) lymphoma classification scheme. The overall progression-free survival (PFS) and overall survival (OS) were 133 and 183 days, respectively. Treatment with a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) protocol was associated with an improved PFS (144 days) and OS (194 days) when compared with dogs that received other medical therapies (P = .005 and P = .002, respectively); the absence of pleural effusion at diagnosis was associated with an increased OS but not PFS. These results suggest that while the prognosis for dogs with mediastinal lymphoma is poor, survival may be improved with treatment using a CHOP-based protocol.

Potency and stability of compounded formulations of chlorambucil, melphalan and cyclophosphamide.

BACKGROUND: Oral chemotherapy agents are frequently compounded in veterinary medicine however, the potency of some formulations have been shown to vary from that of Food and Drug Administration (FDA)-approved products. AIMS: The objective of this study was to evaluate the potency and stability of three compounded oral chemotherapeutics commonly prescribed to be administered over time. MATERIALS & METHODS: Compounded chlorambucil 1 mg, cyclophosphamide 5 mg and melphalan 1 mg were obtained and for potency tested upon receipt and 6 weeks later. RESULTS: Potency ranged from 71 to 104% for chlorambucil and 58 to 109% for melphalan; 1/4 and 2/4 samples were <90% of labelled strength at baseline and 6 weeks, respectively, for both drugs. Potency of cyclophosphamide ranged from 92 to 107% with all samples +/-10% of labelled strength at all time points. DISCUSSION/CONCLUSION: These results demonstrate variability of compounded chemotherapy products, and highlight the need to consider both potency and stability when prescribing orally compounded chemotherapy.

Clinical presentation, treatment and outcome in 31 dogs with presumed primary colorectal lymphoma (2001-2013).

The objective of this multicentre retrospective study was to describe clinical presentation, treatment and outcome and to determine prognostic factors for dogs with presumed primary colorectal lymphoma (PCRL). A total of 31 dogs were included. The predominant features of PCRL were high grade (n = 18) and immunophenotype B (n = 24). Most dogs were substage b (n = 25) with higher prevalence of haematochezia (n = 20). One dog had surgery only. Thirty dogs received chemotherapy; amongst them 13 had surgery or radiotherapy. Progression free survival (PFS) was 1318 days and disease-related median survival time (MST) was 1845 days. Fourteen dogs were alive at the end of the study with a median follow-up time of 684 days (3-4678 days). Younger dogs had longer PFS (P = 0.031) and disease-related MST (P = 0.01). Presence of haematochezia corresponded with longer PFS (P = 0.02). Addition of local treatment to chemotherapy did not significantly improve the outcome (P = 0.584). Canine PCRL has considerably longer PFS and MST than other forms of non-Hodgkin's lymphoma.

BCL2 and MYC are expressed at high levels in canine diffuse large B-cell lymphoma but are not predictive for outcome in dogs treated with CHOP chemotherapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common haematopoietic malignancy in dogs. Recently, MYC and BCL2 expression levels determined with immunohistochemistry (IHC) were found to be prognostic in people with DLBCL. We hypothesized that canine DLBCL can be similarly subdivided into prognostic subtypes based on expression of MYC and BCL2. Cases of canine DLBCL treated with CHOP chemotherapy were retrospectively collected and 43 dogs had available histologic tissue and complete clinical follow-up. Median values of percent immunoreactive versus immunonegative cells were used to determine positive or negative expression status. Completion of CHOP was significantly associated with a positive outcome. Compared with human patients, our canine DLBCL patients had high IHC expression of both MYC and BCL2, and relative expression levels of one or both markers were not associated with clinical outcome.

Chemotherapy effectiveness and mortality prediction in surgically treated osteosarcoma dogs: A validation study.

Canine osteosarcoma is the most common bone cancer, and an important cause of mortality and morbidity, in large purebred dogs. Previously we constructed two multivariable models to predict a dog's 5-month or 1-year mortality risk after surgical treatment for osteosarcoma. According to the 5-month model, dogs with a relatively low risk of 5-month mortality benefited most from additional chemotherapy treatment. In the present study, we externally validated these results using an independent cohort study of 794 dogs. External performance of our prediction models showed some disagreement between observed and predicted risk, mean difference: -0.11 (95% confidence interval [95% CI]-0.29; 0.08) for 5-month risk and 0.25 (95%CI 0.10; 0.40) for 1-year mortality risk. After updating the intercept, agreement improved: -0.0004 (95%CI-0.16; 0.16) and -0.002 (95%CI-0.15; 0.15). The chemotherapy by predicted mortality risk interaction (P-value=0.01) showed that the chemotherapy compared to no chemotherapy effectiveness was modified by 5-month mortality risk: dogs with a relatively lower risk of mortality benefited most from additional chemotherapy. Chemotherapy effectiveness on 1-year mortality was not significantly modified by predicted risk (P-value=0.28). In conclusion, this external validation study confirmed that our multivariable risk prediction models can predict a patient's mortality risk and that dogs with a relatively lower risk of 5-month mortality seem to benefit most from chemotherapy.

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BACKGROUND: Compounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products. HYPOTHESIS/OBJECTIVES: The initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies. ANIMALS: Thirty-seven dogs treated with FDA-approved or compounded lomustine. METHODS: Dogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection. RESULTS: Twenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: These data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products.

Pulse-Administered Toceranib Phosphate Plus Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs.

BACKGROUND: Nonresectable mast cell tumors (MCT) in dogs remain a therapeutic challenge, and investigation of novel combination therapies is warranted. Intermittent administration of tyrosine kinase inhibitors (TKI) combined with cytotoxic chemotherapy may effectively chemosensitize canine MCT while decreasing cost and adverse effects associated with either agent administered as monotherapy. HYPOTHESIS/OBJECTIVES: The primary study objectives were to (1) identify the maximally tolerated dose (MTD), (2) determine the objective response rate (ORR) and (3) describe the adverse event profile of pulse-administered toceranib phosphate (TOC) combined with lomustine. ANIMALS: Forty-seven client-owned dogs with measurable MCT. METHODS: Toceranib phosphate was given PO on days 1, 3 and 5 of a 21-day cycle at a target dosage of 2.75 mg/kg. Lomustine was given PO on day 3 of each cycle at a starting dosage of 50 mg/m(2) . All dogs were concurrently treated with diphenhydramine, omeprazole, and prednisone. RESULTS: The MTD of lomustine was established at 50 mg/m(2) when combined with pulse-administered TOC; the dose-limiting toxicity was neutropenia. Forty-one dogs treated at the MTD were evaluable for outcome assessment. The ORR was 46% (4 complete response, 15 partial response) and the overall median progression-free survival (PFS) was 53 days (1 to >752 days). On multivariate analysis, variables significantly associated with improved PFS included response to treatment, absence of metastasis, and no previous chemotherapy. CONCLUSIONS AND CLINICAL IMPORTANCE: Combined treatment with pulse-administered TOC and lomustine generally is well tolerated and may be a reasonable treatment option for dogs with unresectable or metastatic MCT.

Evidence that the death of macrophage foam cells contributes to the lipid core of atheroma.

Sections of human atherosclerotic lesions of different stages show that, in early lesions, the acellular lipid core is usually immediately adjacent to the deepest edge of a collection of macrophage foam cells. Advanced lesions with a large lipid core have variable numbers of macrophage foam cells, close to the lateral edges, or shoulders, of the core. In both early and advanced lesions, some of the macrophages nearest the core appear to be dying. Lipid cores contain two materials which in earlier lesions are found only in macrophages, namely ceroid and CD68 antigen, but do not contain recognisable smooth muscle cell actin. It is concluded that death of macrophage foam cells contributes to the origin and slow enlargement of the lipid core. The cause of macrophage death is not yet certain, but is under investigation.

A hormonal assessment of bovine parturient paresis: evidence for a role of oestrogen.

A comparative assessment was made of the hormonal control of calcium homeostasis in eight dairy cows which developed parturient paresis and in seven normal animals from the same herd. Plasma levels of calcium, phosphorus, magnesium, free hydroxyproline, 25-hydroxycholecalciferol (25-OHD), 1,25-dihydroxycholecalciferol (1,25-(OH)2D), parathyroid hormone, calcitonin, prolactin and oestrogen were monitored from 30 days prepartum to 15 days post partum. Prepartum levels of plasma calcium, hydroxyproline and calcitonin were depressed in the paretic animals, and plasma levels of phosphorus and oestrogen were elevated. Plasma levels of 25-OHD remained stable in both groups, whereas levels of 1,25-(OH)2D, parathyroid hormone and prolactin rose sharply at parturition. Plasma hydroxyproline, an index of bone resorption, began to rise 2 days prepartum in the control cows but not until 2 days post partum in the paretic cows. The data indicate that bone resorption was inhibited in the paretic group at the onset of lactation, and that a decreased capacity for bone resorption is a major factor in the susceptibility of some cows to this disease. The failure of the paretic animals to resorb bone was not associated with an inability to synthesize the calcium-mobilizing hormones parathyroid hormone or 1,25-(OH)2D, or to regulate the production of calcitonin. However, hypocalcaemia in the affected animals was associated with a significantly higher plasma level of oestrogen (a known inhibitor of bone resorption) in the immediate prepartum period. Following parturition, plasma levels of oestrogen fell rapidly and active bone resorption ensued in the paretic animals.

Effects of insulin-like growth factor-I and its analogues on bovine hydrogen peroxide release by neutrophils and blastogenesis by mononuclear cells.

The biological potencies of recombinant human insulin-like growth factor-I (IGF-I) and two of its analogues were examined for hydrogen peroxide release by neutrophils and blastogenesis by mononuclear cells. The binding affinities of these peptides for bovine serum IGF-binding proteins (IGFBPs) and IGF-I receptors on bovine neutrophils and mononuclear cells were also investigated. Relative to control treatment containing no IGF-I, preincubation of neutrophils with 12.5 micrograms/l of IGF-I, des(1-3)IGF-I (an analogue of human IGF-I lacking the N-terminal tripeptide Gly-Pro-Glu) and long R3 IGF-I (an analogue of human IGF-I with arginine replacing glutamate at position 3 of human IGF-I and the N-terminal extension Met-Phe-Pro-Ala-Met-Pro-Leu-Ser-Ser-Leu-Phe-Val-Asn) increased the release of H2O2 by 65%, 64% and 32% respectively. However, the difference in stimulating the release of H2O2 between long R3 IGF-I and other two (IGF-I and des(1-3)IGF-I) was reduced at a dosage of 100 micrograms/l. In the absence or presence of 2.5% fetal calf serum (FCS), 100 micrograms/l of IGF-I, des(1-3)IGF-I but not long R3 IGF-I significantly stimulated thymidine incorporation into mononuclear cells. In addition, des(1-3)IGF-I was more potent than IGF-I in stimulating thymidine incorporation into mononuclear cells in the presence of 2.5% FCS.(ABSTRACT TRUNCATED AT 250 WORDS)

Receptor binding and growth-promoting activity of insulin-like growth factor-I in a bovine mammary epithelial cell line (MAC-T3).

Insulin-like growth factor-I (IGF-I) has been known to be mitogenic to a variety of cell types, although a growth-regulatory role for IGF-I on bovine mammary epithelial cells has not been fully investigated. In the present study, we examined the receptor binding of IGF-I and its effect on growth in a bovine mammary epithelial cell line (MAC-T3). Specific receptors for IGF-I were detected on cultured bovine mammary epithelial cells. Competitive binding revealed that half-maximal inhibition of 125I-labelled IGF-I binding by IGF-I was approximately 3 micrograms/l. Dissociation rate constant of the IGF-I receptor was 3.10 +/- 0.06 nmol/l (S.E.M.) with a receptor site concentration of 366 +/- 8 fmol/mg protein for the average of three experiments. IGF-I exerted a positive mitogenic effect on MAC-T3 cells according to both direct DNA assay and thymidine incorporation assay. Moreover, the mitogenic effect of IGF-I on MAC-T3 cells was enhanced by the addition of fetal calf serum in the culture media. The present results suggest that the bovine mammary epithelial cell line (MAC-T3) provides a useful model system with which to study the biological actions of insulin-like growth factors on the bovine mammary secretory tissue in vitro.

A binding assay for 25-hydroxycalciferols and 24R,25-dihydroxycalciferols using bovine plasma globulin.

The concentrations of the 25-hydroxy and 24R, 25-dihydroxy derivatives of vitamin D were determined in 100 microliter l plasma samples using calciferol binding globulin from bovine plasma. Sufficient quantities of 24R, 25-dihydroxy vitamin D were found in bovine, porcine, chicken and human plasma to interfere in the assay of 25-hydroxy vitamin D in unfractionated extracts. No metabolites of vitamin D could be found in rainbow trout plasma.

The effect of amniotic fluid ingestion on the nociception of cows.

The effect of the ingestion of the afterbirth on the nociception of cows was studied in two experiments. In both trials, the dependent variable was the thermal threshold of the animal, recorded as temperature and measured using nociceptive tests (NT). In the first experiment, 32 animals were randomly distributed in a 2 x 2 factorial design. The drug factor was an intravenous injection of morphine sulfate or of a saline solution. The fluid factor was the orogastric infusion of amniotic fluid or water. A pretreatment NT was considered as a baseline. Other NTs were performed after the drug injection and after the fluid infusion. In the second experiment, 28 multiparous Holstein cows were randomly assigned to 2 x 2 factorial treatments. The factors were amniotic fluid, either removed or not from the calves' surface immediately after delivery; and placenta, either left available or removed. A NT was performed before and 1, 6 and 36 h after the calf's delivery. In experiment 1, the morphine dose used did not produce an increase of the thermal threshold (p > 0.17) and neither did the amniotic fluid on the morphine-treated cows (p > 0.83). However, the amniotic fluid had an effect (p < 0.04) on the group injected with saline solution. In experiment 2, a linear rise occurred (p < 0.001) in the pain tolerance of the cows as parturition approached. Placenta ingestion and placenta and amniotic fluid ingestion had no effect (p < 0.26) on the thermal threshold of the cows. However, cows ingesting amniotic fluid had a significantly higher thermal threshold in the 1-h test than in the 6-h and 36-h tests (p < 0.004). The nociception of the cows not receiving amniotic fluid did not change across the same periods (p > 0.587). The results indicate that the ingestion of amniotic fluid enhances the ongoing opioid-mediated analgesia at parturition in bovines.

Function of bovine mammary macrophages as antigen-presenting cells.

The ability of mammary macrophages treated with Staphylococcus aureus to induce antigen-specific T-cell proliferation was compared to that of the autologous blood monocytes. Induction of T-cell proliferation has been correlated with changes in major histocompatibility complex (MHC) class II antigen expression and interleukin 1 (IL-1) production by mammary macrophages and blood monocytes. The present study showed that both monocytes and mammary macrophages treated with S. aureus induced T-cell proliferation. However, there was a 3-fold decrease (P less than 0.05) in T-cell proliferation in macrophage cultures compared to those of blood monocytes, when these cells were treated with S. aureus. Mammary macrophages, the cells less effective in stimulating T-cell proliferation, expressed lower levels (2-fold) of MHC class II molecules and produced less IL-1 (3-fold) than blood monocytes. These data suggest that S. aureus may affect macrophage-T cell interaction by modulating the expression of MHC class II molecules and the synthesis of IL-1 by macrophages.