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M Alsina

Publications and source records attributed to M Alsina.

At least 19 recordsLinked to original sources
PubMed2006

Spectrum of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease: clinical relevance of lymphocytic enteritis.

BACKGROUND: Limited data on a short series of patients suggest that lymphocytic enteritis (classically considered as latent coeliac disease) may produce symptoms of malabsorption, although the true prevalence of this situation is unknown. Serological markers of coeliac disease are of little diagnostic value in identifying these patients. AIMS: To evaluate the usefulness of human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy for the detection of gluten-sensitive enteropathy in first-degree relatives of patients with coeliac disease and to assess the clinical relevance of lymphocytic enteritis diagnosed with this screening strategy. PATIENTS AND METHODS: 221 first-degree relatives of 82 DQ2+ patients with coeliac disease were consecutively included. Duodenal biopsy (for histological examination and tissue transglutaminase antibody assay in culture supernatant) was carried out on all DQ2+ relatives. Clinical features, biochemical parameters and bone mineral density were recorded. RESULTS: 130 relatives (58.8%) were DQ2+, showing the following histological stages: 64 (49.2%) Marsh 0; 32 (24.6%) Marsh I; 1 (0.8%) Marsh II; 13 (10.0%) Marsh III; 15.4% refused the biopsy. 49 relatives showed gluten sensitive enteropathy, 46 with histological abnormalities and 3 with Marsh 0 but positive tissue transglutaminase antibody in culture supernatant. Only 17 of 221 relatives had positive serological markers. Differences in the diagnostic yield between the proposed strategy and serology were significant (22.2% v 7.2%, p<0.001). Relatives with Marsh I and Marsh II-III were more often symptomatic (56.3% and 53.8%, respectively) than relatives with normal mucosa (21.1%; p = 0.002). Marsh I relatives had more severe abdominal pain (p = 0.006), severe distension (p = 0.047) and anaemia (p = 0.038) than those with Marsh 0. The prevalence of abnormal bone mineral density was similar in relatives with Marsh I (37%) and Marsh III (44.4%). CONCLUSIONS: The high number of symptomatic patients with lymphocytic enteritis (Marsh I) supports the need for a strategy based on human leucocyte antigen-DQ2 genotyping followed by duodenal biopsy in relatives of patients with coeliac disease and modifies the current concept that villous atrophy is required to prescribe a gluten-free diet.

Adolescent↗
PubMed2004

A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma.

In a phase 2 open-label study of the novel proteasome inhibitor bortezomib, 54 patients with multiple myeloma who had relapsed after or were refractory to frontline therapy were randomized to receive intravenous 1.0 or 1.3 mg/m(2) bortezomib twice weekly for 2 weeks, every 3 weeks for a maximum of eight cycles. Dexamethasone was permitted in patients with progressive or stable disease after two or four cycles respectively. Responses were determined using modified European Group for Blood and Marrow Transplantation criteria. The complete response (CR) + partial response (PR) rate for bortezomib alone was 30% [90% confidence interval (CI), 15.7-47.1] and 38% (90% CI, 22.6-56.4) in the 1.0 mg/m(2) (8 of 27 patients) and 1.3 mg/m(2) (10 of 26 patients) groups respectively. The CR + PR rate for patients who received bortezomib alone or in combination with dexamethasone was 37% and 50% for the 1.0 and 1.3 mg/m(2) cohorts respectively. The most common grade 3 adverse events were thrombocytopenia (24%), neutropenia (17%), lymphopenia (11%) and peripheral neuropathy (9%). Grade 4 events were observed in 9% (five of 54 patients). Bortezomib alone or in combination with dexamethasone demonstrated therapeutic activity in patients with multiple myeloma who relapsed after frontline therapy.

Adult↗
PubMed2001

Bisphosphonates in multiple myeloma.

BACKGROUND: Multiple myeloma is a disease characterized by the neoplastic proliferation of a clone of plasma cells that can lead to bone destruction. Bisphosphonates are specific inhibitors of osteoclastic activity. Therefore, there is a pharmacological basis for their use in multiple myeloma. However, the exact clinical role of bisphosphonates in multiple myeloma remains unclear. OBJECTIVES: Primary: to determine whether adding bisphosphonates to standard therapy in multiple myeloma decreases skeletal-related morbidity (pathological fractures), skeletal-related mortality and overall mortality. Secondary: to determine the effects of bisphosphonates on pain, quality of life and incidence of hypercalcemia. SEARCH STRATEGY: We searched MEDLINE (1966 - June 2001), LILACS (1982 - June 2001), EMBASE (1974 - December 2000) and the Cochrane Controlled Trials Register (all years, latest Issue 03/2001) to identify all randomized trials in multiple myeloma. All of these references were accessed in order to identify trials related to the use of bisphosphonates in myeloma. All relevant references in each article were also scanned. We also performed a handsearch of relevant meeting proceedings from 1993 to 2000. Additionally, manufacturers of bisphosphonates and researchers in the field were contacted. SELECTION CRITERIA: Randomised trials with a parallel design on the use of bisphosphonate in myeloma compared with placebo or no treatment as a control group. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility, methodological quality and abstracted data. A third reviewer checked all data after the extraction was completed. Statistical heterogeneity was tested using random and fixed effect models. All pooled data are reported using Peto odds ratios and, when appropriate, as absolute risk reduction and the number needed to treat to prevent or to cause a pathological event. MAIN RESULTS: Eleven trials were included with 1113 patients analysed in bisphosphonates groups, and 1070 analysed in control groups. There was no significant statistical heterogeneity among trials for the endpoints selected for comparison in this review. The pooled analysis of the published evidence demonstrated the beneficial effect of bisphosphonates on prevention of pathological vertebral fractures [OR=0.59 (95% confidence interval (CI) 0.45-0.78); P=0.0001] and on amelioration of pain [OR = 0.59 (95%CI 0.46-0.76); P=0.00005]. However, the analysis of the effect of bisphosphonates on pain was based on clinically heterogeneous data and must be interpreted with caution. Although there was no statistical heterogeneity between groups, the benefit was most apparent with clodronate and pamidronate. In absolute terms, the result may be interpreted to mean that 10 (95%CI 7-20) patients with multiple myeloma should be treated to prevent one vertebral fracture, and 11 (95%CI 7-28) to prevent one patient experiencing pain. We found no significant effect of bisphosphonates on mortality, on the reduction of non-vertebral fractures or on the incidence of hypercalcemia. There were no significant adverse effects associated with the administration of bisphosphonates. Our results are based on the extraction of published data, which were sometimes poorly reported, and thus the results should be understood as the best possible summation of available evidence. REVIEWER'S CONCLUSIONS: Adding bisphosphonates to the treatment of myeloma reduces pathological vertebral fractures and pain but - from the published evidence - not mortality. On current evidence, clodronate or pamidronate may be the preferred agents.

Bone Diseases↗
PubMed2001

Ibandronate decreases bone disease development and osteoclast stimulatory activity in an in vivo model of human myeloma.

The benefits of bisphosphonate therapy for multiple myeloma bone disease have been clearly documented. However, the effects of bisphosphonates on the osteoclast stimulatory activity (OSA) that is present in the marrow of patients with multiple myeloma, even before the bone disease is detectable, are unknown. Therefore, we examined the effects of ibandronate (IB) treatment prior to the development of bone disease in a murine model of human myeloma. Sublethally irradiated severe combined immunodeficient (SCID) mice were transplanted with ARH-77 cells on day 0. These ARH-77 mice were treated daily with subcutaneous injections of IB started before or at different times after tumor injection as follows: group 1 was started on day -7; group 2 on day 0; group 3 on day +7; group 4 on day +14 after IB administration; and group 5 (control) received no IB. Mice were sacrificed after they developed paraplegia. The onset of paraplegia was delayed in group 1 vs all other groups (mean day 27 vs day 32; p = 0.0098). The number of lytic lesions and the bone surface area of resorption (mm(2)) were significantly decreased in groups 1, 2, and 3, which were treated early with IB, when compared with groups 4 and 5 (p = 0.003 and 0.002, respectively). OSA, as measured by the capacity of bone marrow plasma from ARH-77 mice to induce osteoclast (OCL) formation in human bone marrow cultures, was decreased proportionally to the length of IB treatment. Group 1 had the lowest OSA compared with the other groups (p = 0.003). However, all mice eventually developed paraplegia, and at time of sacrifice, tumor burden was not grossly different among the groups. Interestingly, macroscopic abdominal tumors were more frequent in mice treated with IB. These data demonstrate that early treatment of ARH-77 mice with IB prior to development of myeloma bone disease decreases OSA and possibly retards the development of lytic lesions, but not eventual tumor burden.

Animals↗
PubMed2001

Periodontal pathogens produce quorum sensing signal molecules.

Different species of bacteria important in the composition of dental plaque were tested for production of extracellular autoinducer-like activities that stimulate the expression of the luminescence genes in Vibrio harveyi. Several strains of Prevotella intermedia, Fusobacterium nucleatum, and Porphyromonas gingivalis were found to produce such activities. Interestingly, these bacteria belong to the same phylogenetic group, and they are periodontal pathogens important in the development of periodontal disease. They specifically produce extracellular signaling molecule related autoinducer-2 from V. haveyi. Nevertheless, they seem to be unable to produce homologues of acyl-homoserine lactones. Furthermore, Escherichia coli DH5alpha can be complemented by the introduction of a P. gingivalis gene with high homology to the luxS gene, which has been called luxS(P.g.).

Amino Acid Sequence↗
PubMed2001

Improved, low-cost selective culture medium for Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans is considered to be one of the major oral putative pathogens, especially in cases of juvenile periodontitis. This microorganism requires nutritionally complex media for growth, and therefore the media for its primary isolation usually include blood agar or serum in their base. In this study we present a new medium, Dentaid-1, which improves the detection of A. actinomycetemcomitans in periodontal samples. In its composition, blood and serum have been omitted, hence reducing its cost and making it a more restrictive medium against the growth of other microorganisms with high nutritional requirements. The growth yields of pure cultures of the bacteria on Dentaid-1 were comparable to those on nonselective blood agar. Moreover, clinical efficacy was evaluated in subgingival samples from 77 subjects with adult periodontitis. Dentaid-1 detected A. actinomycetemcomitans in 24 subjects, while a previously described tryptic soy-serum-bacitracin-vancomycin agar detected the microorganism in only 19 subjects (79.1%). Dentaid-1 is a low-cost, noninhibitory formula for the improved diagnosis and monitoring of patients subgingivally infected by this important oral putative pathogen.

Actinobacillus Infections↗
PubMed2001

Antisense inhibition of macrophage inflammatory protein 1-alpha blocks bone destruction in a model of myeloma bone disease.

We recently identified macrophage inflammatory protein 1-alpha (MIP-1alpha) as a factor produced by multiple myeloma (MM) cells that may be responsible for the bone destruction in MM (1). To investigate the role of MIP-1alpha in MM bone disease in vivo, the human MM-derived cell line ARH was stably transfected with an antisense construct to MIP-1alpha (AS-ARH) and tested for its capacity to induce MM bone disease in SCID mice. Human MIP-1alpha levels in marrow plasma from AS-ARH mice were markedly decreased compared with controls treated with ARH cells transfected with empty vector (EV-ARH). Mice treated with AS-ARH cells lived longer than controls and, unlike the controls, they showed no radiologically identifiable lytic lesions. Histomorphometric analysis demonstrated that osteoclasts (OCLs) per square millimeter of bone and OCLs per millimeter of bone surface of AS-ARH mice were significantly less than in EV-ARH mice, and the percentage of tumors per total bone area was also significantly decreased. AS-ARH cells demonstrated decreased adherence to marrow stromal cells, due to reduced expression of the alpha(5)beta(1) integrin and diminished homing capacity and survival. These data support an important role for MIP-1alpha in cell homing, survival, and bone destruction in MM.

Animals↗
PubMed2000

Macrophage inflammatory protein 1-alpha is a potential osteoclast stimulatory factor in multiple myeloma.

This study was designed to determine if macrophage inhibitory protein-1 alpha (MIP-1 alpha), a recently described osteoclast (OCL) stimulatory factor,(1) was present in marrow from patients with multiple myeloma (MM) and possibly involved in the bone destructive process. MIP-1 alpha, but not interleukin-1 beta (IL-1 beta), tumor necrosis factor-beta (TNF-beta), or interleukin-6 (IL-6), messenger RNA was elevated in freshly isolated bone marrow from 3 of 4 patients with MM compared to normal controls. Furthermore, enzyme-linked immunosorbent assays of freshly isolated bone marrow plasma detected increased concentrations of hMIP-1 alpha (range, 75-7784 pg/mL) in 8 of 13 patients (62%) with active myeloma, in 3 of 18 patients (17%) with stable myeloma (range, 75-190.3), as well as in conditioned media from 4 of 5 lymphoblastoid cell lines (LCLs) derived from patients with MM. Mildly elevated levels of MIP-1 alpha were detected in 3 of 14 patients (21%) with other hematologic diagnoses (range, 80.2-118.3, median value of 96 pg/mL) but not in normal controls (0 of 7). MIP-1 alpha was not detected in the peripheral blood of any patients with MM. In addition, recombinant hMIP-1 alpha induced OCL formation in human bone marrow cultures. Importantly, addition of a neutralizing antibody to MIP-1 alpha to human bone marrow cultures treated with freshly isolated marrow plasma from patients with MM blocked the increased OCL formation induced by these marrow samples but had no effect on control levels of OCL formation. Thus, high levels of MIP-1 alpha are expressed in marrow samples from patients with MM, but not in marrow from patients with other hematologic disorders or controls, and support an important role for MIP-1 alpha as one of the major factors responsible for the increased OCL stimulatory activity in patients with active MM. (Blood. 2000;96:671-675)

Bone Marrow↗
PubMed2000

Kaposi's sarcoma-associated herpesvirus gene sequences are detectable at low copy number in primary amyloidosis.

Primary amyloidosis (AL), like multiple myeloma (MM), results from a clonal proliferation of plasma cells. Recent detection of Kaposi's sarcoma-associated herpesvirus (KSHV) gene sequences in MM patients, although controversial, suggested that KSHV may also be present in AL. In the present study, we assayed for KSHV gene sequences in patients with primary AL independently in 2 laboratories. Nested polymerase chain reaction (PCR) was performed on DNA isolated from 21 bone marrow (BM) core biopsy samples to amplify orf26 and orf72, 2 regions of the KSHV genome. Eighteen of 21 (86%) BM core biopsy samples were KSHV PCR positive. BM aspirates from 16 of these 21 AL patients were cultured for 4-6 weeks to generate long term bone marrow stromal cells (LT-BMSCs), and 13 of 16 (81%) LT-BMSCs were also KSHV PCR positive. Results in all but 1 sample were consistent in the 2 laboratories. Sequencing of the PCR products in the 2 laboratories confirmed 94-98% and 95-98% homology to the published orf 26 and orf 72 KSHV gene sequences respectively, with interpatient base pair differences. Despite the presence of KSHV gene sequences, only 4/18 (22%) KSHV PCR positive patients demonstrated KSHV lytic antibodies by immunoblot assay. A sensitive assay performed on the BCBL-1 cell line confirmed the presence of KSHV at a very low copy number in AL. PCR using patient specific light chain gene primers also amplified DNA isolated from 2 AL BM core biopsies and 3 AL LT-BMSCs which were KSHV PCR positive, suggesting the presence of clonotypic cells. Our results therefore demonstrate KSHV gene sequences albeit at a very low copy number in the majority of BM core biopsies and LT-BMSCs from AL patients, and serological responses in only a minority of cases. Ongoing studies to identify viral transcripts and gene products will determine the biological relevance of KSHV in AL disease pathogenesis.

Adult↗
PubMed1999

Successful PBSC mobilization with high-dose G-CSF for patients failing a first round of mobilization.

PBSC are the preferred source of stem cells for autologous transplantation. However, regardless of the mobilization procedure used, 10%-20% of patients fail to collect an adequate number to ensure prompt engraftment. There is as yet no standard mobilization procedure for patients who fail a first mobilization attempt. Here, we describe a highly efficient strategy to obtain an adequate number of stem cells for patients who failed a first mobilization attempt. Seventy-four patients with various hematologic malignancies underwent initial mobilization with various regimens including hematopoietic growth factors with or without chemotherapy. In 72% of patients, > or =2 x 10(6) CD34+ stem cells/kg were collected in the initial mobilization attempt, and patients engrafted in a median of 10 days for neutrophils and 12 days for platelets. Eighteen patients failed to mobilize adequate numbers of stem cells, defined as the inability to collect 0.2 x 10(6) CD34+ stem cells/kg/day in the first 2-3 days. These patients had their apheresis halted. Patients were immediately given G-CSF (32 microg/kg/day) for 4 days as a second attempt at mobilization. Eighty-eight percent of these patients achieved the target of > or =2 x 10(6) CD34+ cells/kg, with a median duration of apheresis of 5 days (including the first and second mobilizations). The mean CD34+ cells/kg/day increased after administration of high-dose G-CSF from 0.16 after the first mobilization attempt to 0.61 (p = 0.0002) after the second mobilization. All patients engrafted in a median of 11 and 13 days for neutrophils and platelets, respectively. We conclude that patients whose apheresis yield is <0.4 x 10(6) CD34+ cells/kg after the first two apheresis collections can be successfully mobilized if high-dose G-CSF is administered immediately and continued until achieving > or =2 x 10(6) CD34+ stem cells/kg.

Adult↗
PubMed1999

Paraneoplastic pemphigus: a case of long-term survival associated with systemic lupus erythematosus and polymyositis.

A 35-year-old man presented with a generalized bullous eruption and oral ulceration. He had been diagnosed as having systemic lupus erythematosus and pelvic Castleman disease (hyaline-vascular type) in the past. Histologic, direct and indirect immunofluorescence and immunoprecipitation studies confirmed a diagnosis of paraneoplastic pemphigus (PNP). Initially several medical treatments were tried unsuccessfully. The pelvic tumor was surgically removed and the mucocutaneous lesions slowly regressed. Four years after presentation, he developed polymyositis which was completely controlled with short courses of corticosteroids. There was no evidence of relapse of PNP or lupus erythematosus at that time. At the 6-year follow-up he showed no clinical evidence of PNP, lupus erythematosus or polymyositis without requiring immunosuppressive therapy. This case emphasizes the fact that patients with benign-neoplasm-associated PNP may undergo complete remission of the autoimmune disease upon complete excision of the tumor. This case also stresses the possible association of PNP with other autoimmune diseases such as lupus erythematosus and polymyositis.

Adult↗
PubMed1998

Antibodies to Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in patients with multiple myeloma.

Kaposi's sarcoma-associated herpesvirus (KSHV) serologic assays were used to detect specific antibodies to KSHV lytic and latent antigens in 27 patients with multiple myeloma, 27 control patients with other cancers, and 50 random blood donors. Antibodies to KSHV recombinant minor capsid antigen orf65 were found in 81% of patients with multiple myeloma, 22% of control patients with other cancers, and 6% of the blood donors. Antibodies to KSHV latent nuclear antigens were found in 52% of patients with multiple myeloma, 26% of control patients with other cancers, and 2% of the blood donors. All of the 11 patients with progressive multiple myeloma were KSHV-seropositive. Antibodies to Epstein-Barr virus nuclear antigen 1 were present in 89% of patients with multiple myeloma, 93% of control patients with other cancers, and 88% of the blood donors. These data support the possible association of KSHV infection with multiple myeloma, particularly with progressive disease.

Antibodies, Viral↗
PubMed1998

Evaluation of topotecan in resistant and relapsing multiple myeloma: a Southwest Oncology Group study.

PURPOSE: Topotecan is a topoisomerase I inhibitor with antitumor activity against hematologic and solid tumor malignancies. We evaluated its activity in refractory and relapsing multiple myeloma patients who had received one prior chemotherapeutic regimen. PATIENTS AND METHODS: Toptecan 1.25 mg/m2/d was administered as a 30-minute infusion for 5 days repeated every 3 weeks. Granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d subcutaneously was administered after the first course of treatment if neutropenia was dose-limiting. RESULTS: Forty-six patients entered the study, with 43 patients eligible. The major toxicity was granulocytopenia with grade 3 or better occurring in 40 of 43 patients treated; 21 of 43 patients developed grade 3 or greater thrombocytopenia. Other significant toxicity included mild nausea in 23 patients and mild vomiting in 13 patients. The overall response rate (partial response or better) was 16% (95% confidence interval, 7% to 31%), with responses occurring in both relapsed and refractory patients. Responses have lasted 70 to 477+ days, with a median progression-free survival duration of 13 months and median survival time of 28 months. CONCLUSION: Topotecan has activity in refractory and relapsing multiple myeloma. Future investigation of topotecan in multiple myeloma including combination therapy and the study of other topoismerase I inhibitors is warranted.

Adult↗
PubMed1997

Radiation therapy in AIDS-related cutaneous Kaposi's sarcoma.

BACKGROUND: Treatment of cutaneous Kaposi's sarcoma associated with AIDS depends on localization, extension, associated symptoms and the patient's general condition. The most frequent sites of involvement are the face and neck. The aim of this retrospective study was to evaluate the response rate as well as the cosmetic results comparing two different schedules of palliative radiation treatment. METHODS: 251 Skin lesions in 22 patients were treated with irradiation using 100 kV X-ray energy. Applied doses varied between 8 Gy/1 fraction and 30 Gy/10 fractions. The mean age of patients was 38 years (28-59 years). According to Mitsuyasu's staging, 2 patients had stage I, 8 stage II and 12 patients stage IV. The lesions were localized on the face (n = 190), lower extremities (n = 28), upper extremities (n = 24) and the thorax (n = 9). The total given dose was 30 Gy in 68 lesions (27%), 21 Gy in 11 lesions (4.4%), 20 Gy in 2 lesions (0.8%) and 8 Gy in 170 lesions (67.8%). RESULTS: Complete response with or without residual pigmentation was achieved in 95.2% of lesions, while 4.4% had a partial response and 0.4% no response. Pain was completely relieved in all patients. CONCLUSIONS: Radiotherapy can be recommended as palliative treatment to relieve physical discomfort (pain) and to improve the cosmetic results in patients with AIDS-related Kaposi's sarcoma. Doses ranging from 8 Gy/1 fraction to 30 Gy/10 fractions, tailored to the individual patient's need, permit to achieve an excellent local control with minimal toxicity.

AIDS-Related Opportunistic Infections↗
PubMed1996

Development of an in vivo model of human multiple myeloma bone disease.

Osteolytic bone destruction and its complications, bone pain, pathologic fractures, and hypercalcemia, are a major source of morbidity and mortality in patients with multiple myeloma. The bone destruction in multiple myeloma is due to increased osteoclast (OCL) activity and decreased bone formation in areas of bone adjacent to myeloma cells. The mechanisms underlying osteolysis in multiple myeloma in vivo are unclear. We used a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses IgG kappa, as a model for human multiple myeloma, SCID mice were irradiated with 400 rads and mice were injected either with 10(6) ARH-77 cells intravenously (ARH-77 mice) or vehicle 24 hours after irradiation. Development of bone disease was assessed by blood ionized calcium levels, x-rays, and histology. All ARH-77, but none of control mice that survived irradiation, developed hind limb paralysis 28 to 35 days after injection and developed hypercalcemia (1.35 to 1.46 mmol/L) a mean of 5 days after becoming paraplegic. Lytic bone lesions were detected using x-rays in all the hypercalcemic mice examined. No lytic lesions or hypercalcemia developed in the controls. Controls or ARH-77 mice, after developing hypercalcemia, were then killed and bone marrow plasma from the long bones were obtained, concentrated, and assayed for bone-resorbing activity. Bone marrow plasma from ARH-77 mice induced significant bone resorption in the fetal rat long bone resorption assay when compared with controls (percentage of total 45Ca released = 35% +/- 4% v 11% +/- 1%). Histologic examination of tissues from the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen and marked infiltration in vertebrae and long bones, with loss of bony trabeculae and increased OCL numbers. Interestingly, cultures of ARH-77 mouse bone marrow for early OCL precursors (colony-forming unit-granulocyte-macrophage [CFU-GM]) showed a threefold increase in CFU-GM from ARH-77 marrow versus controls (185 +/- 32 v 40 +/- 3 per 2 x 10(5) cell plated). Bone-resorbing human and murine cytokines such as interleukin-6 (IL-6), IL-1 alpha or beta, TGF-alpha, lymphotoxin, and TNF alpha were not significantly increased in ARH-77 mouse sera or marrow plasma, compared with control mice, although ARH-77 cells produce IL-6 and lymphotoxin in vitro. Conditioned media from ARH-77 cells induced significant bone resorption in the fetal rat long bone resorption assay when compared with untreated media (percentage of total 45Ca released = 22% +/- 2% v 11% +/- 1%). This effect was not blocked by anti-IL-6 or antilymphotoxin (percentage of total 45Ca released = 19% +/- 1% and 22% +/- 1%, respectively). Thus, we have developed a model of human multiple myeloma bone disease that should be very useful to dissect the pathogenesis of the bone destruction in multiple myeloma.

Animals↗