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Biomedical subjects

M C Martini

Publications and source records attributed to M C Martini.

49 records · Page 3Linked to original sources
PubMed1982

Isolated osteoclasts and their presumed progenitor cells, the monocyte, in culture.

Osteoclasts were isolated from the endosteal surface of day 19 embryonic chick tibias by mild trypsinization. Osteoclast enrichment was achieved by passing cell suspensions through Nitex screening of selective sizes, including the eventual selective retention of osteoclasts on 12 micrometers polycarbonate filters or by sequential sieving through Nitex screens and fractionation on Percoll gradients. The enrichment procedures produced osteoclast populations of 50-75% based on morphological criteria with the latter isolation method providing populations with less matrix debris. The results of light microscopy, transmission and scanning electron microscopic observations indicate that osteoclasts can be maintained in culture for up to 10 days with retention of osteoclast morphology. This morphology includes a specialized ruffled plasma membrane, large numbers of mitochondria, lysosomes, as well as a multinucleated cytoplasm. Furthermore, acid phosphatase and butyrate esterase histochemical measurements support these morphological observations. In addition, chick hatchling circulating monocytes were isolated and purified by Ficoll-hypaque gradient centrifugation with subsequent adhesion to glass petri dishes. With time in culture, these cells form multinucleated cells, but lack the ultrastructural complexity of the isolated osteoclasts. This report describes a unique culture system to study osteoclast function and illustrates the similarities and differences of this system to the monocyte-to-giant cell culture system.

Animals↗
PubMed1982

Adhesion of osteoclasts and monocytes to developing bone.

Osteoclast resorption of bone matrix during bone development is preceded by cell attachment to bone. An in vitro assay is described that measures adhesion of isolated osteoclasts and their presumed progenitor cell, the monocyte, to embryonic chick bone. Osteoclasts were isolated from day 19 chick tibia and enriched. Circulating chick hatchling monocytes were purified by Ficoll-hypaque sedimentation and attachment to plastic. Isolated cells were labeled with (32P)-KH2PO4 to quantitate cell attachment. In one series of experiments, labeled cells were inoculated into vessels containing day 19 tibias with either endosteal or periosteal bone surface exposed. Labeled cells were also inoculated into chambers containing day 6 (cartilage cores), day 12 (bone and cartilage cores), or day 19 embryonic tibias (bone). Cultures of stage 24 chick limb mesenchyme and embryonic chick skin fibroblasts served as controls. Results demonstrate that twice as many osteoclasts and monocytes adhere to bone as compared to fibroblasts and stage 24 limb mesenchymal cells. Furthermore, there does not appear to be selective adhesion to the endosteal as compared to periosteal bone surfaces. When the data is calculated on the basis of cell attachment per area of each substrate, the day 12 cores had slightly higher number of osteoclasts and monocytes attached compared to day 19 bones; day 6 cartilage cores bound few cells. These observations suggest that osteoclasts and monocytes have a high affinity to bone which seems to be influenced by the developmental age and composition of the substrate.

Animals↗
PubMedDate not supplied

Plasma alpha1-antichymotrypsin in Alzheimer's disease; relationships with APOE genotypes.

Inflammatory processes are thought to be important contributors to the pathogenesis of Alzheimer's disease (AD). alpha1-antichymotrypsin (ACT) is a proteinase inhibitor characteristic of acute-phase inflammation and has been identified in amyloid plaques. We analyzed the plasma ACT levels in a sample of subjects with late-onset AD and correspondent controls. Plasma ACT was higher in AD patients (62.8 +/- 20.2 mg/dl) than in controls (58.8 +/- 18.1 mg/dl), but not significantly (P = 0.13). In the AD patients regression analysis showed a positive linear relationship between ACT levels and duration of the disease (P = 0.037). Increased ACT concentrations (64.6 +/- 21.2 mg/dl) were also found in patients with greater cognitive impairment (MMSE scores < 20), but since this factor depends on the duration of the disease as well, our present data seem to indicate a complex relationship involving elevated ACT levels, disease duration and cognitive impairment. Plasma ACT was found to differ significantly according to APOE genotypes (P = 0.017), the highest levels being associated to E3-E3 homozygotes (66.1 +/- 17.8 mg/dl) and the lowest to E4-E3 subjects (53.1 +/- 18.2 mg/dl). In patients not carrying APOE*4 allele the ACT levels were higher than in controls (P = 0.014), and the relationship between ACT and disease duration was stronger than that observed in the total AD sample (P = 0.003), but it was absent in those carrying APOE*4 (P = 0.67). Taken together our results seem to suggest that inflammation is a relevant factor in AD pathogenesis for subjects with E3-E3 and E3-E2 genotypes but less important for APOE*4 carrying subjects.

Aged↗
PubMedDate not supplied

Polymorphisms of the apolipoprotein E gene regulatory region and of the LDL receptor gene in late-onset Alzheimer's disease in relation to the plasma lipidic pattern.

Two new polymorphisms in the regulatory region of the apolipoprotein E gene, -491 A/T and -427 T/C, have been reported to be associated with the risk of Alzheimer's disease (AD). Moreover, in vitro studies suggest that the two polymorphisms modulate the levels of apoE protein expression. We examined these two polymorphisms, as well as the MspI polymorphism in the LDL receptor gene, in a series of elderly patients with late-onset sporadic AD and in an age-matched control group but failed to find any kind of association between these genetic features and an increased risk of AD. In the same samples we investigated the relationships between various genotypes and plasma lipid levels. Since the well-known effect of the three-allelic APOE polymorphism on plasma lipid levels could mask the effect of other polymorphisms, the analyses were performed taking into account the APOE genotype. The two regulatory region polymorphisms had significant effects only on the apoE levels. The -427 TT homozygotes had lower, and the -491 AA homozygotes had higher levels of apoE than other genotypes. This result confirmed in vivo the already observed in vitro effects of -491 A/T and -427 T/C polymorphisms on APOE promoter transcription activity.

Age of Onset↗
PubMedDate not supplied

Paclitaxel plus ifosfamide in advanced ovarian cancer: a multicenter phase II study.

BACKGROUND: While ovarian cancer is one of the most sensitive cancers to cytotoxic drugs, with objective response rates of 60-80% routinely being reported in previously untreated patients, the majority of individuals with advanced disease ultimately relapse. Paclitaxel, a new and novel antimicrotubule agent, has shown activity as a salvage therapy in epithelial ovarian cancer. More importantly, in a prior study, it has been shown to be active in tumors that have displayed resistance to platinum compounds, with a reported response rate of 20%. Ifosfamide has shown activity in the treatment of patients who previously demonstrated clinical resistance to a platinum-cyclophosphamide combination. Recently, a synergistic activity of Taxol combined with ifosfamide has been reported in ovarian cell lines. Based on these data, a phase I/II study of a combination treatment with paclitaxel and ifosfamide was performed. PATIENTS AND METHODS: Thirty-one patients with recurrent ovarian cancer or ovarian cancer refractory to cisplatin (CDDP)-containing regimens were treated with paclitaxel at a dose of 135 mg/m2 on day 1; ifosfamide was administered at 1 g/m2 on days 2 and 3 for the first cycle and 1.5 and 2 g/m2 with the same schedule in cycles 2 and 3, respectively. In the absence of toxicity, the dose of ifosfamide was maintained at 2 g/m2 for the last three cycles. Cytotoxic therapy was repeated every 3 weeks. RESULTS: A 30% overall objective response rate was achieved in the 30 patients assessable for response. Among 21 platinum-resistant patients, 4 partial responses (19%) were observed, while in the 9 platinum-sensitive patients 2 complete responses and 3 partial responses (55%) were observed. Myelosuppression was the predominant toxicity. Leukopenia (WHO grade 3-4) occurred in 10% of patients who received ifosfamide at a dose of 1 g/m2 and in 18% of patients treated with ifosfamide at 1.5 g/m2. CONCLUSION: Our results confirmed a low activity of paclitaxel in platinum-resistant patients. The results of this combination treatment with paclitaxel-ifosfamide in our platinum-sensitive patients support further investigations in a randomized study of the combination regimen against paclitaxel alone or retreatment with organoplatinum compounds.

Aged↗
PubMedDate not supplied

Combination of epirubicin and lonidamine for treatment of advanced breast cancer.

AIMS AND BACKGROUND: In vitro and in vivo studies have shown that lonidamine potentiates the cytotoxic effect of anthracyclines in simultaneous and sequential combination. On the basis of such evidence, we evaluated the activity and toxicity of a combination of epirubicin plus lonidamine in advanced breast cancer. METHODS: Between January 1991 and November 1993, 33 patients with advanced breast cancer, age < 75 years and PS < 2, were treated with epirubicin (75 mg/m2 i.v. on day 1, every 3 weeks), plus lonidamine (450 mg/day orally from day 1 continuously until disease progression). RESULTS: Thirty patients were evaluable for response: 4 achieved complete response (13%) and 8 partial response (27%) (total response rate = 40%), 6 (20%) had stabilization of disease, and 12 (40%) progression of disease. The median duration of response was 10 months (range, 4-24+ months). This scheme was tolerated, with a mild additional toxicity related to lonidamine: only WHO grade III myalgia in 1 patient (3%) and epigastralgia in 3 patients (9%). CONCLUSIONS: Although some patients seem to have benefited from the combination at the dose levels of the drug used in the study, the therapeutic advantages of addition of lonidamine remain unclear.

Adult↗
PubMedDate not supplied

[Limits on the use of propylene glycol in topical preparations].

The authors define some limits for useful concentrations of propylene glycol (P.G.) by determination of inhibition produced in cell respiration from (crushed) mouse liver and in human cutaneous fibroblastic proliferation. They conclude that P.G. is able to inhibit both these physicological mechanisms from concentration as weak as 5.5% and 2% respectively. They give a method for analytical determination of P.G. in cosmetic and pharmaceutical products using gas liquid chromatography. This method is useful for a wide range of concentrations.

Administration, Topical↗
PubMedDate not supplied

Dietary modulation of serum platelet-derived growth factor-AB levels.

Epidemiological studies have demonstrated that diets high in vegetables and fruit are associated with a decreased risk of cancer and, possibly cardiovascular disease. Certain constituents of vegetables and fruit inhibit the in vitro activity of platelet-derived growth factor (PDGF), a potent mitogen implicated in both cancer and cardiovascular disease. Few studies have measured PDGF in relationship to diet in vivo. Specifically, there are no data regarding the changes in PDGF levels of mitogenic activity after a dietary intervention. In this study, 19 young, healthy individuals consumed four (9-day) experimental diets in random order: (a) control diet alone; (b) control diet plus carotenoid-rich vegetables; (c) control diet plus cruciferous vegetables; and (d) control diet plus soy foods. Compared to the control diet, there was a significant elevation in PDGF-AB serum levels when the individuals were consuming the soy diet (P = 0.016). Increased PDGF-AB levels were also noted for the carotenoid diet. There was no change from baseline levels when individuals were consuming the cruciferous diet. Overall, mitogenic activity did not change on any of the experimental diets. This study suggests that high soy and carotenoid diets increase serum levels of PDGF-AB. This may represent an additional mechanism by which diet influences individual risk of cancer; further investigation into the role of diet and growth factors is warranted.

Cardiovascular Diseases↗
PubMedDate not supplied

Plasma carotenoids as biomarkers of vegetable intake: the University of Minnesota Cancer Prevention Research Unit Feeding Studies.

High vegetable intake has been associated with a decreased risk for various human cancers in epidemiological studies. Carotenoids are plant compounds that may both possess chemopreventive activity and be useful biomarkers of vegetable and fruit intake. Nineteen men and women were randomized into a controlled cross-over feeding study to measure the effect of vegetable intake on plasma carotenoid concentrations. Participants consumed each of 4 experimental diets for 9 days. The control diet consisted of commonly consumed foods and was essentially carotenoid free. High vegetable diets (carotenoid, cruciferous, and soy) consisted of the control diet plus carrots and spinach (carotenoid), broccoli and cauliflower (cruciferous), and tofu and FriChik (soy). Plasma carotenoid concentrations were highest on the carotenoid and cruciferous diets. When compared to the control, mean plasma alpha-carotene, beta-carotene, and lutein concentrations were 5.2, 3.3 and 2.2 times higher on the carotenoid diet, respectively (P < 0.001). Mean plasma lutein concentrations were 2.1 times higher on the cruciferous versus the control diet (P < 0.001). There were no differences between diets in plasma beta-cryptoxanthin and lycopene concentrations. These data indicate that plasma alpha-carotene, beta-carotene, and lutein may be useful biomarkers of carotenoid-rich food intake and that lutein may act as an intake biomarker of commonly consumed vegetables in the Cruciferae family. These findings should prove useful in undertaking dietary intervention trials because they suggest the feasibility of monitoring intake of some plant foods and of distinguishing among plant food groups.

Adult↗