scholarly journals 1725. Shear Forces Induce a Transient, Calcineurin-Dependent Hyper-Virulent Phenotype in Mucorales via Soluble Factors

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S632-S633
Author(s):  
Sebastian Wurster ◽  
Alexander M Tatara ◽  
Nathaniel D Albert ◽  
Antonios G Mikos ◽  
Ashraf S Ibrahim ◽  
...  
Keyword(s):  
Survival Rates ◽  
Time Lapse ◽  
Mucor Circinelloides ◽  
In Vivo Studies ◽  
Epigenetic Alterations ◽  
Shear Forces ◽  
Natural Catastrophes ◽  
Sequencing Studies ◽  
Virulent Phenotype

Abstract Background Myocutaneous mucormycosis is encountered in settings of extreme mechanical forces such as combat-related blast injuries or natural catastrophes. It is unclear whether the virulence of Mucorales is affected by mechano-biological factors such as shear forces (SF). Methods Spores of clinical strains of Rhizopus arrhizus, Rhizomucor pusillus, and Mucor circinelloides (107/mL in PBS) were either kept in static culture (control) or exposed to shear forces (SF) by magnetic stirring for 30 minutes. Mycelial expansion was monitored in the IncuCyte time-lapse microscopy system. For in vivo studies, the dorsal thorax of wild-type Drosophila melanogaster flies (n = 66–76 per condition) was pricked with a needle dipped in control or SF-exposed spore solutions. Flies were also infected with non-exposed spores suspended in cell-free supernatant taken from SF-exposed spores. Survival was monitored for 7 days post-infection. Results Growth rates and morphogenesis of all isolates were not altered by SF. However, SF-exposed spores of all tested Mucorales isolates exhibited increased pathogenicity in the fly model (7-day survival: SF 8–14%, control 36–44%, P < 0.001). Introducing different resting periods after SF resulted in gradual attenuation of the hyper-virulent phenotype, with survival rates of infected flies returning to the level seen with non-SF-exposed spores after 120 min post-SF resting (Panel A). To gain a mechanistic insight, we added cyclosporine A (CsA, 100 µg/mL) during shear challenge. Compared with SF-exposed spores, CsA addition improved 7-day survival of R. arrhizus-infected flies from 1% to 29% (P < 0.001), whereas the pathogenicity of non-SF-exposed spores was not influenced by CsA. Interestingly, supernatants from SF-exposed R. arrhizus rendered non-exposed spores hyper-virulent (Panel B, P = 0.003). Conclusion SF induces a transient hypervirulent phenotype of Mucorales. Our findings suggest that soluble mediators contribute to increased pathogenicity. Largely attenuated hyper-virulence in the presence of CsA corroborated the previously described relevance of the calcineurin pathway in fungal mechano-biology. RNA sequencing studies are in progress to identify epigenetic alterations in Mucorales following SF. Disclosures All authors: No reported disclosures.

scholarly journals Mechanistic Understanding of Curcumin’s Therapeutic Effects in Lung Cancer

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 2989 ◽  
Author(s):  
Wan Nur Baitty Wan Mohd Tajuddin ◽  
Nordin H. Lajis ◽  
Faridah Abas ◽  
Iekhsan Othman ◽  
Rakesh Naidu
Keyword(s):  
Lung Cancer ◽  
Curcuma Longa ◽  
Survival Rates ◽  
In Vivo Studies ◽  
Therapeutic Effects ◽  
Epigenetic Alterations ◽  
Anti Cancer ◽  
Lung Cancer Therapy

Lung cancer is among the most common cancers with a high mortality rate worldwide. Despite the significant advances in diagnostic and therapeutic approaches, lung cancer prognoses and survival rates remain poor due to late diagnosis, drug resistance, and adverse effects. Therefore, new intervention therapies, such as the use of natural compounds with decreased toxicities, have been considered in lung cancer therapy. Curcumin, a natural occurring polyphenol derived from turmeric (Curcuma longa) has been studied extensively in recent years for its therapeutic effects. It has been shown that curcumin demonstrates anti-cancer effects in lung cancer through various mechanisms, including inhibition of cell proliferation, invasion, and metastasis, induction of apoptosis, epigenetic alterations, and regulation of microRNA expression. Several in vitro and in vivo studies have shown that these mechanisms are modulated by multiple molecular targets such as STAT3, EGFR, FOXO3a, TGF-β, eIF2α, COX-2, Bcl-2, PI3KAkt/mTOR, ROS, Fas/FasL, Cdc42, E-cadherin, MMPs, and adiponectin. In addition, limitations, strategies to overcome curcumin bioavailability, and potential side effects as well as clinical trials were also reviewed.

Assessing CD97 and CD99 As Markers of Leukaemia Initiating Cells in Paediatric ALL

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1882-1882 ◽  
Author(s):  
Charlotte Victoria Cox ◽  
Paraskevi Diamanti ◽  
Allison Blair
Keyword(s):  
Functional Capacity ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Survival Rates ◽  
In Vivo Studies ◽  
Nsg Mice ◽  
Early Treatment Response ◽  
Current Therapies

Abstract Abstract 1882 Overall survival rates in paediatric acute lymphoblastic leukaemia (ALL) have dramatically improved but around 20% do not respond to current therapies and subsequently relapse. Leukaemia initiating cells (LIC) are the topic of much investigation, as these cells can self-renew and may have the potential to cause relapse. It has been shown that multiple subpopulations of ALL cells have the ability to initiate the disease in immune deficient mouse models. Therefore, treatment should be targeted at all cells with this capacity, if the disease is to be eradicated. Minimal residual disease (MRD) detection is an invaluable tracking tool to assess early treatment response and recent studies have highlighted potential markers that may improve the sensitivity of MRD detection by flow cytometry. CD97 and CD99 are two markers which were over expressed in paediatric ALL. Incorporating these markers into investigations of LIC may allow discrimination of leukaemia cells from normal haemopoietic stem cells (HSC). In this study we evaluated the expression of CD34 in combination with CD97 in B cell precursor (BCP) ALL cases and CD99 in T-ALL cases and subsequently assessed the functional capacity of the sorted subpopulations in vitro and in vivo. Ten ALL samples (6 B-ALL & 4 T-ALL) with a median age 7 years (range 2–15 years) were studied. One B-ALL case and 3 T-ALL cases were considered high risk by molecular assessment of MRD at day 28 of treatment. Flow cytometric analyses of the ALL samples and 8 normal haemopoietic cell samples demonstrated that both CD97 and CD99 were over expressed in ALL patients (78.9±14.8% & 76.4±32.8%, respectively) when compared to normal haemopoietic cells (14.1±25.4%; p=0.001, 47.1±10%; p=0.03, respectively). Cells were sorted for expression/lack of expression of these markers and proliferation of the sorted cells was assessed in suspension culture over a 6 week period. In the B-ALL patients the CD34+/CD97+ subpopulation represented the bulk of leukaemia cells (65.2±32.1%), the CD34−/CD97+ the smallest fraction (3.3±2.4%) with the CD34+/CD97− and CD34−/CD97− subpopulations representing 21.1±31.5% and 10.5±5.8% of cells, respectively. When the functional capacity of these subpopulations was assessed in vitro greatest expansion was observed in cells derived from CD34+/CD97− subpopulation (2–173 fold) from 9.4×103 at initiation up to 1.5×106 cells at week 6. Expansion was also observed, to a lesser extent in the CD34−/CD97− subpopulation (3.4–28 fold) from 8×103 up to 1.4×106 cells. No expansion was observed in cultures of CD34+/CD97+ and CD34−/CD97− subpopulations but cells were maintained throughout the culture period. These sorted subpopulations were also inoculated into NOD/LtSz-SCID IL-2Rγc null (NSG) mice to evaluate repopulating capacity. To date, engraftment has been achieved with 3 subpopulations; CD34+/CD97+ (3–28.8% CD45+), CD34+/CD97− (0.5–25.5% CD45+) and CD34−/CD97+ (23.8% CD45+) cells. When the functional capacity of T-ALL cases was assessed the CD34+/CD99+ subpopulation represented the bulk of cells at sorting (51.87±47.2%), the CD34+/CD99- subpopulation was the smallest (0.9±0.8%) and the CD34−/CD99+ and CD34−/CD99− subpopulations represented 32.1±38.9% and 27.2±33.4% of cells, respectively. Greatest expansion was observed in cultures of CD34+/CD99- cells (4.6–1798 fold) from 7.5×103 up to 2.6×106 cells at week 6. The other 3 subpopulations expanded to a lesser extent (1.3–216 fold) from 5×103 up to 1.8×106 cells. When the functional capacity of these cells was assessed in NSG mice, engraftment was achieved in all subpopulations; CD34+/CD99+ (87–90.5% CD45+), CD34+/CD99− (1.5–84.9% CD45+), CD34−/CD99+ (31.3–98.6% CD45+) and CD34−/CD99− (3–92.9% CD45+). In some cases, cells recovered from BM of NSG inoculated with CD99− cells had high expression of CD99, typical of the patient samples at diagnosis, indicating that the inoculated CD99− cells had differentiated in vivo. Studies are ongoing to assess the self-renewal capacity of these subpopulations by serial transplantation. The findings to date indicate that targeting CD97 and CD99, either alone or in combination with CD34 would not eliminate all cells with the capacity to initiate and maintain B-ALL and T-ALL, respectively. Further developments in therapy may require targeting leukaemogenic pathways, rather than only cell surface markers to improve survival outcome in paediatric ALL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals In Vitro and In Vivo Activities of Syn2836, Syn2869, Syn2903, and Syn2921: New Series of Triazole Antifungal Agents

2001 ◽  
Vol 45 (9) ◽  
pp. 2420-2426 ◽  
Author(s):  
S. M. Salama ◽  
H. Atwal ◽  
A. Gandhi ◽  
J. Simon ◽  
M. Poglod ◽  
...  
Keyword(s):  
Antifungal Agents ◽  
Survival Rates ◽  
Systemic Infection ◽  
Kinetic Studies ◽  
The Other ◽  
In Vivo Studies ◽  
Infection Model ◽  
Time Kill

ABSTRACT The in vitro and in vivo activities of four azole compounds belonging to a new series of 2(2,4-difluorophenyl)-3-(4-substituted piperazin-1-yl)-1-(1,2,4-triazol-1-yl) butanol antifungal agents is described. The compounds were selected from a library of azole compounds synthesized by our group. The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB). The MICs at which 90% of the isolates were inhibited (MIC90s) for the four test compounds for strains of Candida spp. ranged from <0.048 to 0.78 μg/ml. All compounds were also active against FLC-resistant Candida albicans and otherCandida sp. strains. Moreover, MIC90s for strains of Cryptococcus neoformans,Aspergillus spp., Trichophyton spp., andMicrosporum spp. were also low and ranged from <0.048 to 0.39 μg/ml. The test compounds produced a fungistatic pattern during the time-kill kinetic studies. In vivo studies indicated that all four test compounds have good efficacies against C. albicans in a murine systemic infection model and significantly improved the survival rates of the infected mice. The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC. The compounds were also evaluated against anAspergillus fumigatus systemic infection. Syn2903 was also superior to ITC, whereas the efficacy data for the other compounds were similar to those for ITC. It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing.

scholarly journals CITCO as an Adjuvant Facilitates CHOP-Based Lymphoma Treatment in hCAR-Transgenic Mice

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2520
Author(s):  
Ritika Kurian ◽  
William Hedrich ◽  
Bryan Mackowiak ◽  
Linhao Li ◽  
Hongbing Wang
Keyword(s):  
Transgenic Mice ◽  
Constitutive Androstane Receptor ◽  
Plasma Concentrations ◽  
Survival Rates ◽  
Pharmacokinetic Profile ◽  
In Vivo Studies ◽  
Chop Regimen ◽  
Transgenic Mouse Line

Non-Hodgkin’s lymphoma (NHL) is a malignant cancer originating in the lymphatic system with a 25–30% mortality rate. CHOP, consisting of cyclophosphamide (CPA), doxorubicin, vincristine, and prednisone, is a first-generation chemotherapy extensively used to treat NHL. However, poor survival rates among patients in advanced stages of NHL shows a need to improve this standard of care treatment. CPA, an integral component of CHOP, is a prodrug that requires CYP2B6-mediated bioactivation to 4-hydroxy-CPA (4-OH-CPA). The expression of CYP2B6 is transcriptionally regulated by the constitutive androstane receptor (CAR, NRi13). We have previously demonstrated that the induction of hepatic CYP2B6 by CITCO, a selective human CAR (hCAR) agonist, results in CHOP’s enhanced antineoplastic effects in vitro. Here, we investigate the in vivo potential of CITCO as an adjuvant of CPA-based NHL treatment in a hCAR-transgenic mouse line. Our results demonstrate that the addition of CITCO to the CHOP regimen leads to significant suppression of the growth of EL-4 xenografts in hCAR-transgenic mice accompanied by reduced expression of cyclin-D1, ki67, Pcna, and increased caspase 3 fragmentation in tumor tissues. CITCO robustly induced the expression of cyp2b10 (murine ortholog of CYP2B6) through hCAR activation and increased plasma concentrations of 4-OH-CPA. Comparing to intraperitoneal injection, oral gavage of CITCO results in optimal hepatic cyp2b10 induction. Our in vivo studies have collectively uncovered CITCO as an effective facilitator for CPA-based NHL treatment with a pharmacokinetic profile favoring oral administration, promoting CITCO as a promising adjuvant candidate for CPA-based regimens.

scholarly journals Thiosemicarbazide Derivatives Decrease the ATPase Activity of Staphylococcus aureus Topoisomerase IV, Inhibit Mycobacterial Growth, and Affect Replication in Mycobacterium smegmatis

2021 ◽  
Vol 22 (8) ◽  
pp. 3881
Author(s):  
Aleksandra Kowalczyk ◽  
Agata Paneth ◽  
Damian Trojanowski ◽  
Piotr Paneth ◽  
Jolanta Zakrzewska-Czerwińska ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Atpase Activity ◽  
Mycobacterium Smegmatis ◽  
Time Lapse ◽  
In Vivo Studies ◽  
Bacterial Cells ◽  
Small Molecular Weight ◽  
Topoisomerase Iv ◽  
Replication Process

Compounds targeting bacterial topoisomerases are of interest for the development of antibacterial agents. Our previous studies culminated in the synthesis and characterization of small-molecular weight thiosemicarbazides as the initial prototypes of a novel class of gyrase and topoisomerase IV inhibitors. To expand these findings with further details on the mode of action of the most potent compounds, enzymatic studies combined with a molecular docking approach were carried out, the results of which are presented herein. The biochemical assay for 1-(indol-2-oyl)-4-(4-nitrophenyl) thiosemicarbazide (4) and 4-benzoyl-1-(indol-2-oyl) thiosemicarbazide (7), showing strong inhibitory activity against Staphylococcus aureus topoisomerase IV, confirmed that these compounds reduce the ability of the ParE subunit to hydrolyze ATP rather than act by stabilizing the cleavage complex. Compound 7 showed better antibacterial activity than compound 4 against clinical strains of S. aureus and representatives of the Mycobacterium genus. In vivo studies using time-lapse microfluidic microscopy, which allowed for the monitoring of fluorescently labelled replisomes, revealed that compound 7 caused an extension of the replication process duration in Mycobacterium smegmatis, as well as the growth arrest of bacterial cells. Despite some similarities to the mechanism of action of novobiocin, these compounds show additional, unique properties, and can thus be considered a novel group of inhibitors of the ATPase activity of bacterial type IIA topoisomerases.

scholarly journals New Ti-Alloys and Surface Modifications to Improve the Mechanical Properties and the Biological Response to Orthopedic and Dental Implants: A Review

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
Yvoni Kirmanidou ◽  
Margarita Sidira ◽  
Maria-Eleni Drosou ◽  
Vincent Bennani ◽  
Athina Bakopoulou ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Survival Rates ◽  
Biological Response ◽  
Surface Treatments ◽  
Titanium Implants ◽  
In Vivo Studies ◽  
Advantages And Disadvantages ◽  
Ti Alloys

Titanium implants are widely used in the orthopedic and dentistry fields for many decades, for joint arthroplasties, spinal and maxillofacial reconstructions, and dental prostheses. However, despite the quite satisfactory survival rates failures still exist. New Ti-alloys and surface treatments have been developed, in an attempt to overcome those failures. This review provides information about new Ti-alloys that provide better mechanical properties to the implants, such as superelasticity, mechanical strength, and corrosion resistance. Furthermore, in vitro and in vivo studies, which investigate the biocompatibility and cytotoxicity of these new biomaterials, are introduced. In addition, data regarding the bioactivity of new surface treatments and surface topographies on Ti-implants is provided. The aim of this paper is to discuss the current trends, advantages, and disadvantages of new titanium-based biomaterials, fabricated to enhance the quality of life of many patients around the world.

scholarly journals Phenolic Compounds – An Emerging Group of Natural Compounds against Leukaemia: in vitro, in vivo and Clinical Applications

2021 ◽  
Author(s):  
Lucienne Gatt ◽  
Pierre Schembri Wismayer
Keyword(s):  
Phenolic Compounds ◽  
Kinase Inhibitors ◽  
Survival Rates ◽  
Absolute Lymphocyte Count ◽  
In Vivo Studies ◽  
Beneficial Effects ◽  
Anticancer Properties ◽  
All Trans Retinoic Acid

Leukaemia is the most common cancer in children under 15 years of age as well as the most common blood cancer in people older than 55. The use of all trans retinoic acid (ATRA) in combination with arsenic trioxide (ATO) for acute promyelocytic leukaemia (APL) and tyrosine kinase inhibitors for chronic myeloid leukaemia (CML) respectively, have improved survival rates. However, new, natural therapies are constantly being sought after to overcome issues with resistance, side effects and specificity. As a result of their range of health benefits, including anticancer properties, phenolic compounds have been extensively studied over the past two decades. One on hand, in vitro and in vivo studies highlight both the inhibitory as well as differentiation inducing effects of phenolics on different leukaemia types. On the other hand, clinical trials to date have shown their beneficial effects (decrease in the absolute lymphocyte count and lymphadenopathy) in CLL (Chronic lymphoblastic leukaemia) patients. Promising therapeutic candidates for future use include epigallocatechin-3-gallate, coumarin, and gallic acid, with the latter ideally used in combination with the conventional drugs daunorubicin and cytarabine.

scholarly journals Cubic and spherical nanoparticles for detection and therapy of cancer

2016 ◽  
Author(s):  
◽  
Dhananjay Suresh
Keyword(s):  
Cancer Detection ◽  
Sirna Delivery ◽  
Survival Rates ◽  
Endocytic Pathway ◽  
In Vivo Studies ◽  
Spherical Nanoparticles ◽  
Targeted Capture ◽  
Photon Coupling

Cancer is the leading cause of high mortality rates. Cancer patients require advanced treatment due to lack of early prevention and diagnosis. Moreover, progression of the disease is unpredictable and personalized therapy options are being explored. Existing cancer therapy leads to drug resistance that worsens patient survival rates, and thus disease management is challenging. This necessitates the need to understand the underlying cause, early detection of possible biomarkers, monitor the disease state and develop effective therapeutics. Current innovations in cancer detection and therapy includes use of newer class of smart nanomaterials. These advances in nanoscale materials, due to their unique size, chemical and physical properties, make them ideal for nanomedicinal and nanoelectronic applications. The work performed in this thesis describes the design and the synthesis of cubic and spherical nanoparticles, and their subsequent applications toward energy interactions, biochemical interactions and cellular targeting. Details of receptor mediated endocytic mechanism, targeted capture of circulating tumor cells (CTC), athermal mechanism of controlled release of biomolecules from nanoparticles using femtosecond pulses, and targeted siRNA delivery using nanoparticles have been explained. Mechanistic studies showed that receptor targeting follows a clathrin mediated endocytic pathway. Receptor-targeted nanoparticles showed effective capture of EpCAM-negative CTCs. The cubic shaped nanoparticles were found to enhance the plasmon-photon coupling to efficiently release biomolecules. Spherical nanoparticle mediated siRNA delivery resensitized drug resistant NSCLC by downregulating two important oncogenes, AXL and FN14 as observed by both in vitro and in vivo studies. Additionally, the study highlights drug resensitization following the effective knockdown of AXL using CRISPR based gene editing. Overall, the results demonstrate the application of nanoparticles for advanced diagnostics and therapeutics.

scholarly journals In vitro and in vivo effects of rifabutin alone or combined with atovaquone against Toxoplasma gondii.

1996 ◽  
Vol 40 (9) ◽  
pp. 2015-2020 ◽  
Author(s):  
S Romand ◽  
C Della Bruna ◽  
R Farinotti ◽  
F Derouin
Keyword(s):  
Toxoplasma Gondii ◽  
Synergistic Effects ◽  
Survival Rates ◽  
Culture Method ◽  
In Vivo Studies ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Brain ◽  
Acute Toxoplasmosis

The efficacy of rifabutin (RIFA) alone or in combination with atovaquone (ATO) was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were performed with MRC5 fibroblast tissue cultures, with quantification of Toxoplasma growth by enzyme-linked immunosorbent assay. For in vivo studies, mice were acutely infected with 10(4) tachyzoites of the virulent RH strain and were then treated perorally for 10 days from day 1 or day 4 postinfection. The efficacy of each drug regimen was assessed by determination of survival rates and sequential titration of parasites in blood, brain, and lungs by a tissue culture method. In vitro, RIFA was inhibitory for Toxoplasma growth at concentrations between 0.5 and 20 micrograms/ml; the 50% inhibitory concentration was estimated to be 1.68 micrograms/ml. When RIFA and ATO were combined, synergistic effects were noted for RIFA at 20 micrograms/ml combined with ATO at 0.01 or 0.02 microgram/ml and RIFA at 1, 2, or 5 micrograms/ml combined with ATO at 0.02 microgram/ml. In vivo, administration of RIFA at 200 mg/kg of body weight per day from day 1 to day 10 resulted in a 100% protection during treatment, with clearance of parasites from the blood, brain, and lungs. After the cessation of therapy, relapses occurred in the brain and lungs; the mortality was 46% at the end of the experiment (day 30). Among the mice treated with RIFA at 200 mg/kg/day from day 4 to day 14, no death was recorded during the treatment period and a marked reduction in parasite burdens was observed in blood and tissues; however, relapses occurred and 10% of mice survived until day 30. Administration of RIFA at 200 mg/kg/day in combination with ATO at 100 mg/kg/day resulted in a marked prolongation of survival compared with that for mice that received ATO or RIFA alone. However, in mice receiving the combination, parasite burdens in blood and organs were similar to those in mice treated with RIFA alone. These results confirmed the activity of RIFA in the treatment of acute toxoplasmosis and the potential of the combination of RIFA-ATO since the two drugs act synergistically against Toxoplasma gondii.

Ultrastructure of melanocyte-keratinocyte interactions and pigment transfer in vitro

1978 ◽  
Vol 36 (2) ◽  
pp. 650-651
Author(s):  
Raul I. Garcia ◽  
Evelyn A. Flynn ◽  
George Szabo
Keyword(s):  
Direct Injection ◽  
Skin Pigmentation ◽  
Freeze Fracture ◽  
Pigment Granule ◽  
Time Lapse ◽  
Ultrastructural Level ◽  
Lanthanum Tracer ◽  
A Cell

Skin pigmentation in mammals involves the interaction of epidermal melanocytes and keratinocytes in the structural and functional unit known as the Epidermal Melanin Unit. Melanocytes(M) synthesize melanin within specialized membrane-bound organelles, the melanosome or pigment granule. These are subsequently transferred by way of M dendrites to keratinocytes(K) by a mechanism still to be clearly defined. Three different, though not necessarily mutually exclusive, mechanisms of melanosome transfer have been proposed: cytophagocytosis by K of M dendrite tips containing melanosomes, direct injection of melanosomes into the K cytoplasm through a cell-to-cell pore or communicating channel formed by localized fusion of M and K cell membranes, release of melanosomes into the extracellular space(ECS) by exocytosis followed by K uptake using conventional phagocytosis. Variability in methods of transfer has been noted both in vivo and in vitro and there is evidence in support of each transfer mechanism. We Have previously studied M-K interactions in vitro using time-lapse cinemicrography and in vivo at the ultrastructural level using lanthanum tracer and freeze-fracture.

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