- I have been a full professor for more than 30 years with a research focus targeting the clinical application of stem ... moreI have been a full professor for more than 30 years with a research focus targeting the clinical application of stem cells in medicine, along with the developing new and improved medications to treat cancer and retroviral infections. In addition, I have been a long time researcher focusing also on the non-psychiatric medical uses of lithium. Focusing on health care education, I also serve as an advisor for students interested in pursuing careers health care. Trained as a clinical laboratory hematologist, I have served in a number of administrative and clinical positions over the years.edit
Research Interests: Immunology and Stem Cell
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dressed in this study was to investigate the impact of wire-less technology on the profession by soliciting input directly from biomedical/clinical laboratorians. Using questionnaires laboratorians were queried how hand-held mobile... more
dressed in this study was to investigate the impact of wire-less technology on the profession by soliciting input directly from biomedical/clinical laboratorians. Using questionnaires laboratorians were queried how hand-held mobile devices would assist in improving diagnosis, treatment strategies and therapeutic outcomes in patients. It questioned whether the healthcare community feels these devices will make healthcare more cost effective and affordable. The questionnaire was distributed to biomedical/clinical laboratorians globally. One hundred and six questionnaires were analyzed and the overall response rate was found to be significant (P value < 0.05). The respondents concluded the use of hand-held mobile devices have and will continue to improve the efficiency of disseminating laboratory data. Devices will assist in biomedical/clinical assessment of patients through more efficient reporting of test results, eventually providing data directly to the patient. Respondents note...
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Effect of lithium on the formation and function of blood cells, V.S.Gallicchio effect of lithium on human lymphocytes, M.J.Messino lithium attenuation of leukophenia associated with cancer chemotherapy, G.H.Lyman and C.C.Williams lithium,... more
Effect of lithium on the formation and function of blood cells, V.S.Gallicchio effect of lithium on human lymphocytes, M.J.Messino lithium attenuation of leukophenia associated with cancer chemotherapy, G.H.Lyman and C.C.Williams lithium, lymphocyte stimulation and the neuroimmune interface, D.A.Hart immunoregulation in patients treated with lithium for affective disorders, D.A.Hart lithium use with carbamazepine - haematological aspects, K.G.Kramlinger and R.M.Post lithium transport in red blood cells of bipolar patients, D.E.Mota de Freitas et al the action of lithium upon sodium, potassium, water and serotonin in blood, M.Uluitu.
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2125 Doxorubicin (DOX) is the lead member of the class of anthracyclines having antitumor activity against hematological and solid cancers, and plays a prominent role in breast cancer therapy. Long term cardiomyopathy hinders clinical use... more
2125 Doxorubicin (DOX) is the lead member of the class of anthracyclines having antitumor activity against hematological and solid cancers, and plays a prominent role in breast cancer therapy. Long term cardiomyopathy hinders clinical use of anthracyclines. The total dosage of Doxorubicin in treatment protocols is limited because of this concern. The prevailing thesis is that Doxorubicin injures the heart by generating damaging free radicals through iron-catalyzed redox cycling. Didox is a unique ribonucleotide reductase (RR) inhibitor possessing free radical scavenging and iron chelating properties while exhibiting anti-cancer activity on its own. Therefore Didox was tested to see if it could decrease DOX toxicity without reducing its anticancer activity. The cardioprotective effects of Didox were assessed, both acutely and chronically in the rat, using a Langendorff model of heart perfusion. Cardiac function, as measured by Rate Pressure Product (RPP), was decreased 40% by DOX alo...
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Resumen del trabajo presentado a la 3rd International Conference on Predictive, Preventive and Personalized Medicine & Molecular Diagnostics, celebrada en valencia (Espana) del 1 al 3 de septiembre de 2015.
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Autism Spectrum Disorder [ASD] is a neuro developmental disorder that is characterized by abnormal social interaction/communication and restricted, repetitive patterns of behavior, interests, or activities. Although there is a lack of... more
Autism Spectrum Disorder [ASD] is a neuro developmental disorder that is characterized by abnormal social interaction/communication and restricted, repetitive patterns of behavior, interests, or activities. Although there is a lack of knowledge surrounding the ASD’s etiology, one common hypothesis posits that the causative pathology is immune system deregulation [ISD]. Patients with ASD experience ISD in the form of overactive microglia and astroglia in the brain, overactive cytokines in the brain and blood plasma, and underactive T lymphocytes in the blood plasma. Mesenchymal stem cells [MSCs] and mononuclear cells, which contain a mixture of MSCs and hematopoietic stem cells [HSCs], are promising candidates for treatment of ASD. MSCs secrete several molecules that may restore injured tissue and anti-inflammatory molecules that may mediate neuro inflammation. MSCs also exhibit immuno modulatory effects which may regulate the immune response observed in ASD.HSCs secrete various cyto...
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Coumarin (1,2-benzopyrone), in combination with cimetidine, has been subjected to separate clinical trials for the treatment of advanced renal cell carcinoma, malignant melanoma, and non-small cell lung cancer. While objective tumor... more
Coumarin (1,2-benzopyrone), in combination with cimetidine, has been subjected to separate clinical trials for the treatment of advanced renal cell carcinoma, malignant melanoma, and non-small cell lung cancer. While objective tumor regressions were observed only in renal carcinoma, no symptomatic or organ dysfunction toxicity was observed in any of the trials. The purpose of the present in vitro study was to determine the concentrations of coumarin and 7-hydroxycoumarin (7-HC) that would be toxic to human peripheral blood mononuclear cells (PB-MNC) and human and murine bone marrow (GM) progenitor stem cells. Coumarin was nontoxic for PB-MNC in concentrations up to 100 micrograms/ml. Concentrations of coumarin or 7-HC greater than or equal to 200 micrograms/ml produced significant suppression of human marrow GM stem cell activity. Coumarin greater than or equal to 25 micrograms/ml produced suppression of murine marrow GM stem cell activity. Differences in human and murine marrow sen...
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Synopsis 1. Lithium erhoht die Zahl der neutrophilen und eosinophilen Gra nulozyten, jedoch wahrscheinlich nicht der Monozyten, basophi len Granulozyten, Thrombozyten, Erythrozyten bzw. Retikulozy ten im peripheren Btut. 2. Lithium... more
Synopsis 1. Lithium erhoht die Zahl der neutrophilen und eosinophilen Gra nulozyten, jedoch wahrscheinlich nicht der Monozyten, basophi len Granulozyten, Thrombozyten, Erythrozyten bzw. Retikulozy ten im peripheren Btut. 2. Lithium erhOht im Knochenmark die Anzahl pluripotenter Stammzellen wie auch die der Granulozyten-Makrophagen-Vor stufen und Megakaryozyten-Vorstufen, senkt hingegen wahr scheinlich die Anzahl der Erythrozytenvorstufen. 3. Als zugrundeliegender Wirkungsmechanismus wird eine direkte wie auch eine indirekte Zellwirkung vermutet, narnlich die Erho hung der Anzah! von Makrophagen, die Wachstumsfaktoren und Zytokine produzieren. Auch spielt hier eine lithiumbedingte er hohte Aktivitat des Knochenmarkgewebes eine Rolle. Die Abnah me der Erythropoese unter Lithium wird moglicherweise durch die Hemmung von cAMP und konsekutiver Hemmung der Pro staglandine der Gruppe E verursacht. 4. Daher kann Lithium bei toxischer Schadigung der Hamatopoese, sei es durch Chemotherapie, Radiatio, antivirale Medikamente oder Granulozytopenie durch Carbamazepin oder Neuroleptika therapeutisch eingesetzt werden. 5. Das Entstehen einer Leukamie durch Lithium konnte bislang wis senschaftlich nicht nachgewiesen werden.
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Doxorubicin (DOX) is a leading member of the class of anthracyclines, antitumor drugs widely used against solid and hematological cancers, especially in breast cancer. Long term cardiomyopathy hinders clinical use of anthracyclines. The... more
Doxorubicin (DOX) is a leading member of the class of anthracyclines, antitumor drugs widely used against solid and hematological cancers, especially in breast cancer. Long term cardiomyopathy hinders clinical use of anthracyclines. The total dosage of anthracyclines in treatment ...
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ObjectiveChimerism can be achieved in a canine model of in utero bone marrow transplantation with ≥1×108 CD34+ haploidentical donor cells per kilogram without graft-versus-host disease.
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Lithium remains the preferred Food and Drug Administration- (FDA-) approved psychiatric drug for treatment of bipolar disorders since its medical establishment more than half a century ago. Recent studies revealed a promising role for... more
Lithium remains the preferred Food and Drug Administration- (FDA-) approved psychiatric drug for treatment of bipolar disorders since its medical establishment more than half a century ago. Recent studies revealed a promising role for lithium in the regulation of inflammation, oxidative stress, and neurodegeneration albeit unclear about its exact mode of action. Thus, the intention of this study is to delineate the regulatory mechanisms of lithium on oxidative stress in lipopolysaccharide- (LPS-) activated macrophages by evaluating its effects on nuclear factor-κB (NF-κB) activity and mRNA expression of multiple oxidative stress-related NF-κB genes. Raw 264.7 macrophages were treated with up to 10 mM lithium, and no change in cell proliferation, viability, growth, and cell adhesion was observed in real time. Pretreatment with low doses of lithium was shown to reduce nitric oxide (NO) production in LPS-activated macrophages. A reduced internal H2DCFDA fluorescence intensity, indicati...
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Research in regenerative medicine and tissue engineering has continued to show advancement towards being a potential cure for autoimmune disorders. Specifically, mesenchymal stem cells show great potential in tissue regeneration and... more
Research in regenerative medicine and tissue engineering has continued to show advancement towards being a potential cure for autoimmune disorders. Specifically, mesenchymal stem cells show great potential in tissue regeneration and repair. Pre-eclampsia is a systematic endothelial dysfunction disorder that leads to hypertension and proteinuria. This occurs when syncytiotrophoblast are under stress and can’t properly remodel the spiral arteries of the placental bed. Mesenchymal stem cells are being used to reverse the damage already done by pre-eclampsia and restore equilibrium. Current research shows promising outcomes when tested on animals. Experiments are being ran to test all aspects of the disorder from regeneration and reconstruction to genetic foundations.
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Adipose-derived stem cells are a promising tool for the future of reconstructive surgeries, regenerative therapies and cosmetic procedures. Their ability to be safely, efficiently and cost-effectively isolated from extracted subcutaneous... more
Adipose-derived stem cells are a promising tool for the future of reconstructive surgeries, regenerative therapies and cosmetic procedures. Their ability to be safely, efficiently and cost-effectively isolated from extracted subcutaneous fat tissue makes them a favorable option for plastic surgeons, who often routinely perform liposuction procedures that provide adequate samples for stromal vascular fraction isolation. The differentiation potential of adipose-derived stem cells is vast and limited only in a developmental potential when compared to embryonic stem cells. Their utilization within clinical trials can be seen in procedures ranging from soft tissue and bony reconstruction, wound and burn healing, peripheral nerve regeneration and cosmetic procedures like skin rejuvenation and breast augmentations. The results from these trials provide evidence that supports future use of these stem cells within these fields of medicine.
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There has been increased concern on many levels focused on the environmental and occupational exposure of heavy metals and their impact on disease, specifically the carcinogenic potential inducing cancer in humans. Because the impact of... more
There has been increased concern on many levels focused on the environmental and occupational exposure of heavy metals and their impact on disease, specifically the carcinogenic potential inducing cancer in humans. Because the impact of heavy metals on human health continues to be a major health concern, research continues to improve our understanding of the carcinogenic potential of these substances. Of particular concern have been human exposure to aluminum, arsenic, beryllium, cadmium, lead, mercury, nickel, and radium and their carcinogenic potential whether contact is via environmental or occupational exposure. This updated review focuses on the carcinogenic mechanisms heavy metals use to induce malignant transformation of cells as well as addressing the overall environmental and occupational hazards of heavy metal exposure.
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Murine acquired immunodeficiency syndrome (MAIDS) induced by a defective LP-BM5 murine leukemia virus (MuLV) produces hematopoietic cytopenias similar to HIV in patients with AIDS. The pathogenesis of MAIDS induced cytopenias remains... more
Murine acquired immunodeficiency syndrome (MAIDS) induced by a defective LP-BM5 murine leukemia virus (MuLV) produces hematopoietic cytopenias similar to HIV in patients with AIDS. The pathogenesis of MAIDS induced cytopenias remains obscure; however, direct ...
Research Interests: Biology, Medicine, Gene expression, Hematopoiesis, Biological Sciences, and 15 moreAntibodies, Hematopoietic Stem Cells, Mice, Animals, Megakaryocytes, Bone marrow, IL, Myeloid Cells, Bone Marrow Cells, Neutralizing antibodies, Interleukin, Neutralization tests, reverse transcriptase polymerase chain reaction, Murine Leukemia Virus, and Reverse transcription polymerase chain reaction
Murine acquired immunodeficiency disease (MAIDS) induced by LPBM5 MuLV is characterized by a late-stage lymphoma and hematopoietic cytopenias similar to those observed in human AIDS. The pathogenesis of MAIDS-related lymphoma/cytopenia is... more
Murine acquired immunodeficiency disease (MAIDS) induced by LPBM5 MuLV is characterized by a late-stage lymphoma and hematopoietic cytopenias similar to those observed in human AIDS. The pathogenesis of MAIDS-related lymphoma/cytopenia is unknown but it has ...
Research Interests: Fluorescence Microscopy, Gene expression, Western blotting, Biological Sciences, Hematopoietic Stem Cells, and 15 moreCell line, Virus, Mice, Animals, Bone marrow, Fibroblast Growth Factor, Viral Infection, Western blot, Stromal Cells, Primary Culture, Virus infection, Bone Marrow Cells, reverse transcriptase polymerase chain reaction, Reverse transcription polymerase chain reaction, and Basic Fibroblast Growth Factor
Since the identification of mesenchymal stem cells, stem cell biology is a greatly researched field of regenerative medicine and tissue engineering therapies and has become an essential part of dentistry. Mesenchymal stem cells are... more
Since the identification of mesenchymal stem cells, stem cell biology is a greatly researched field of regenerative medicine and tissue engineering therapies and has become an essential part of dentistry. Mesenchymal stem cells are multipotent stem cells that can differentiate into many cell types. Dental mesenchymal stem cell populations have been identified in dental pulp, human exfoliated deciduous teeth, periodontal ligament, dental follicle of third molars, tooth germ of third molars, gingiva of periodontium, alveolar bone, and apical papilla. Dental stem cells are the most natural, noninvasive source of stem cells that have been identified, and they have gained recent attention due to their accessibility and the associated relatively low cost of integration into regenerative therapy. Long-term preservation of dental stem cells is becoming a popular consideration and mirrors the ideology of banking umbilical cord blood. This review outlines the recent progress in the mesenchyma...
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We have previously demonstrated that continuous administration of dose-escalation zidovudine (AZT) in either normal or LP-BM5 MuLV immunodeficient virus-infected mice (MAIDS) was associated with the development of anemia, neutropenia, and... more
We have previously demonstrated that continuous administration of dose-escalation zidovudine (AZT) in either normal or LP-BM5 MuLV immunodeficient virus-infected mice (MAIDS) was associated with the development of anemia, neutropenia, and thrombocytopenia. Hematopoietic ...
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Research Interests: Clinical Trial, Medical Microbiology, Spleen, Hematopoietic Stem Cells, Mice, and 12 moreAnimals, Splenomegaly, Combination drug therapy, Hydroxyurea, Antiviral, Ribonucleotide Reductase, Hydroxamic Acids, Antiviral Agents, Bone Marrow Cells, Pharmacology and pharmaceutical sciences, reverse transcriptase inhibitors, and Viral Disease
Murine AIDS (MAIDS) is a disease that shows many similarities to human HIV infection. The etiological agent of MAIDS is a defective murine leukemia virus that seems to be able to induce disease in the absence of viral replication. This... more
Murine AIDS (MAIDS) is a disease that shows many similarities to human HIV infection. The etiological agent of MAIDS is a defective murine leukemia virus that seems to be able to induce disease in the absence of viral replication. This animal model has been useful in stimulating the search of answers to questions and the formation of new hypotheses related
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Recently, the use of the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU) in combination with nucleoside analogs has gained attention as a potential strategy for anti-HIV-1 therapy. However, appeal for the long-term use of HU in... more
Recently, the use of the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU) in combination with nucleoside analogs has gained attention as a potential strategy for anti-HIV-1 therapy. However, appeal for the long-term use of HU in HIV-1 infection may be limited by its propensity to induce hematopoietic toxicity. We report a comparison of the efficacy and bone marrow toxicity of HU (400 and 200 mg/kg/day) with the novel RR inhibitors and free radical-scavenging compounds didox (DX; 3,4-dihydroxybenzohydroxamic acid; 350 mg/kg/day) and trimidox (TX; 3,4,5-trihydroxybenzamidoxime; 175 mg/kg/day) in the murine AIDS (LPBM5 MuLV) model of retrovirus infection. Infected mice received daily drug treatment for 8 weeks. Efficacy was determined by measuring drug effects on retroviral-induced disease progression (i.e. development of splenomegaly and hypergammaglobulinemia) and by evaluating splenic levels of proviral DNA. Bone marrow toxicity was evaluated by measuring peripheral blood indices (WBC, hematocrit and reticulocyte counts), femoral cellularity and by determining the numbers of hematopoietic progenitor cells (CFU-GM, BFU-E) per femur and spleen. Compared to infected controls receiving no drug treatment, disease progression was significantly suppressed by TX, DX and HU. However, HU was associated with mortality and induced significant hematopoietic toxicity in a time- and dose-dependent manner. Conversely, TX and DX effectively inhibited retrovirus-induced disease but did not induce hematopoietic toxicity. These results suggest that due to their reduced hematopoietic toxicity and ability to inhibit disease progression in murine AIDS, TX and DX may offer effective alternatives to HU therapy in HIV-1 infection.
Research Interests: Medical Microbiology, Biology, Medicine, Hematopoietic Stem Cells, Infection Control, and 15 moreMice, Femur, Female, Animals, Bone marrow, Disease Progression, Hydroxyurea, Antiviral, Drug Effects, Ribonucleotide Reductase, Hydroxamic Acids, Drug treatment, Bone Marrow Cells, Pharmacology and pharmaceutical sciences, and Peripheral blood
1. Cancer Biol Ther. 2002 Sep-Oct;1(5):539-45. Didox (a novel ribonucleotide reductase inhibitor) overcomes Bcl-2 mediated radiation resistance in prostate cancer cell line PC-3. Inayat MS, Chendil D, Mohiuddin M, Elford HL, Gallicchio... more
1. Cancer Biol Ther. 2002 Sep-Oct;1(5):539-45. Didox (a novel ribonucleotide reductase inhibitor) overcomes Bcl-2 mediated radiation resistance in prostate cancer cell line PC-3. Inayat MS, Chendil D, Mohiuddin M, Elford HL, Gallicchio VS, Ahmed MM. ...
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1. Oncogene. 2002 Nov 7;21(51):7883-90. Farnesyltransferase inhibitor (L-744,832) restores TGF-beta type II receptor expression and enhances radiation sensitivity in K-ras mutant pancreatic cancer cell line MIA PaCa-2. Alcock ...
Research Interests: Biology, Regulation, Enzyme Inhibitors, Apoptosis, Medicine, and 15 morePancreatic Cancer, Gene expression, Molecular Mechanics, Cell line, Humans, Oncogene, DNA methylation, Clinical Sciences, Sensitivity, Methionine, Irradiation, Radiation Tolerance, Adenocarcinoma, Enzyme Induction, and Pancreatic neoplasms
The world continues to change rapidly and globalization is fostering common social, economic, and political agreements among countries. Agreements by governments have created opportunities to enhance educational and research endeavors... more
The world continues to change rapidly and globalization is fostering common social, economic, and political agreements among countries. Agreements by governments have created opportunities to enhance educational and research endeavors that, by design, will remove barriers that previously have limited the flow of students, educators, researchers, and professionals across borders. Global access has opened the door to mobility in higher education, encouraging the development of educational standards and mutual mechanisms of recognition. Three years ago an eight-institution consortium comprised of four American and four European institutions of higher learning came together in a partnership to provide opportunities for students and faculty to share the educational and research experience internationally. A partnership of this magnitude was constructed despite barriers that were both administrative and cultural in origin. Through a positive approach, a framework for a transatlantic progr...
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The importance of undergraduate coursework in determining medical school student readiness reaches far beyond preparation to take the standardized Medical College Admissions Test (MCAT®). Since medical schools employ a rigorous and... more
The importance of undergraduate coursework in determining medical school student readiness reaches far beyond preparation to take the standardized Medical College Admissions Test (MCAT®). Since medical schools employ a rigorous and fast-paced learning system to instruct prospective medical students on (A) didactic information in the basic sciences and (B) the critical methodology of clinical practice, it is essential for applicants to be well-equipped for the challenge that this type of scholarship requires. A research study investigated current medical students enrolled at the four medical schools in the State of South Carolina: The Medical University of South Carolina (MUSC), University of South Carolina College of Medicine Columbia (USCSOM-Columbia), University of South Carolina College of Medicine Greenville (USCSOM-Greenville) and Edward Via College of Medicine Spartanburg (VCOM-Spartanburg). Questionnaires were distributed in the form of Google surveys to all medical instituti...
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We evaluated the ability of a short course of treatment with the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU) and two novel RR inhibitors Trimidox (TX) and Didox (DX) to influence late-stage murine retrovirus-induced... more
We evaluated the ability of a short course of treatment with the ribonucleotide reductase (RR) inhibitor hydroxyurea (HU) and two novel RR inhibitors Trimidox (TX) and Didox (DX) to influence late-stage murine retrovirus-induced lymphoproliferative disease. LPBM5 murine leukaemia virus retrovirus-infected mice were treated daily with HU, TX or DX for 4 weeks, beginning 9 weeks post-infection, after development of immunodeficiency and lymphoproliferative disease. Drug effects on disease progression were determined by evaluating spleen weight and histology. Effects on haematopoiesis were determined by measuring peripheral blood indices (white blood cells and haematocrit) and assay of femur cellularity and femoral and splenic content of colony-forming units granulocyte-macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E). HU, TX and DX partially reversed late-stage retrovirus-induced disease, resulting in spleen weights significantly below pre-treatment values. Spleen histolog...
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Inhibitors of the cellular enzyme ribonucleotide reductase (hydroxyurea, [HU]) have been proposed as a new therapeutic strategy for the treatment of HIV type-1 (HIV-1) infection. However, HU use may be limited by the frequent development... more
Inhibitors of the cellular enzyme ribonucleotide reductase (hydroxyurea, [HU]) have been proposed as a new therapeutic strategy for the treatment of HIV type-1 (HIV-1) infection. However, HU use may be limited by the frequent development of hematopoietic toxicity. We report here short-term hematopoietic toxicity in mice receiving HU when compared to either of two more potent enzyme inhibitors, didox (DX) and trimidox (TX). High dose HU, DX, and TX monotherapy (500, 460, and 220 mg/kg/day respectively) was administered by daily i.p. injection (Monday-Friday) to C57BL/6 mice for 10 weeks. Effects on hematopoiesis were established by quantitating peripheral blood indices (hematocrit, hemoglobin, mean corpuscular volume, mean cell hemoglobin, mean corpuscular hemoglobin concentration, RBC, and WBC) and numbers of colony-forming units-granulocyte-macrophage (CFU-GM) and BFU-E from bone marrow and spleen. HU produced rapid induction of a macrocytic hypochromic anemia and altered white blood cell kinetics associated with myelosuppression defined as reduced marrow organ cellularity and induction of splenic extramedullary hematopoiesis. Compared to HU, TX and DX induced fewer changes in peripheral blood indices and CFU-GM and BFU-E per hematopoietic organ. In vitro human and murine marrow CFU-GM and BFU-E colony formations were assayed in the presence of dose escalation HU, DX, or TX (0, 1, 10, 50, 100, and 200 microM). HU inhibited colony formation more than either DX or TX. These in vivo and in vitro studies suggest that novel ribonucleotide reductase inhibitors TX and DX may provide an effective alternative to HU in HIV-1 therapy because they demonstrate reduced hematopoietic toxicity.