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Biomedical subjects

M Manna

Publications and source records attributed to M Manna.

At least 19 recordsLinked to original sources
PubMed2005

A cyber medical center.

This paper describes the design and implementation of a Cyber Medical Center (CMC) using web technology. The intention is to overcome the inefficiency of the traditional filing system for patients' medical records, which are considered to be time and space consuming. Another objective is to enhance the interaction between the user - the patient in this case - and the medical center personnel - the doctors and staff. This task is achieved by developing a cyber medical center interfaced with the Internet to provide direct public access. The traditional filing system is replaced by a database system for maintaining the electronic medical records of all patients in the medical center. The doctors or staff can either view the medical records or update them through the Intranet/Internet. This system has been successfully developed, implemented and tested on the Intranet platform. It will be available in a university medical center for practical use.

Computer Simulation↗
PubMed2002

Fate of chronic myeloid leukemia patients treated with allogeneic bone marrow transplantation or chemotherapy and/or interferon at a single center: long-term results.

From April 1981 to February 2000, 105 patients with chronic myeloid leukemia (CML) underwent BMT from HLA-identical related donors at a single center. Eighty-eight patients were in chronic phase (CP), 11 patients in accelerated phase and six patients in blast crisis. Ten of these patients received a second BMT (BMT2). Comparison of BMT in CP with chemotherapy and/or alpha-IFN (n=70) was also made. Patients were given cyclophosphamide (CY) and single-dose TBI (CYTBI, n=38) or busulfan (BU) and CY (BUCY, n=67). Overall 54 patients are alive and 52 of them are disease-free with a median follow-up of 11.3 (range 1.1-19.4) years. Ten-year disease-free survival (DFS) in CP patients was better after BUCY, 61% (95% CI, 47-68%) than after CYTBI, 41% (95% CI, 23-61%) (P=0.07). For 88 patients who received a transplant in CP, results were significantly improved when BMT was performed within 1 year after diagnosis (P=0.02) or at an age < or = 25 years old (P=0.01). Ten-year survival in patients who received BMT in CP was better than in patients treated with chemotherapy (56% vs 10%; P=0.0001) or alpha-IFN-based treatment (33%; P=0.09) with survival curves crossing at 4.2 years and at 4 years, respectively. The probability of DFS after BMT2 was 60% (95% CI, 26-87%). CP patients who received BMT after CYTBI had a higher probability of relapse and transplant-related mortality than patients receiving BUCY (53% and 58% vs 9% and 34%; P=0.002 and P=0.08, respectively). All but six patients are currently on no medication and have resumed all activities without any limitation. These long-term results confirm that allogeneic BMT is the only curative approach for CML patients and should be offered to all patients with a suitable donor as soon after diagnosis as possible.

Adolescent↗
PubMed2000

Inhibition of cellular action of thrombin by N3-cyclopropyl-7-[[4-(1-methylethyl)phenyl]methyl]-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine (SCH 79797), a nonpeptide thrombin receptor antagonist.

A growing body of evidence suggests an important contribution of the cellular actions of thrombin to thrombosis and restenosis following angioplasty. Recently we reported on SCH 79797 (N3-cyclopropyl-7-¿[4-(1-methylethyl)phenyl]methyl¿-7H-pyrrolo[3, 2-f]quinazoline-1,3-diamine) and its analogs as new potent, nonpeptide thrombin receptor antagonists. This study further characterizes the biochemical and pharmacological actions of pyrroloquinazoline inhibitors of protease activated receptor-1 (PAR-1) in human platelets and coronary artery smooth muscle cells (hCASMC). SCH 79797 and its N-methyl analog (SCH 203099) inhibited binding of a high-affinity thrombin receptor-activating peptide ([(3)H]haTRAP, Ala-Phe(p-F)-Arg-ChA-HArg-[(3)H]Tyr-NH(2)) to PAR-1 with IC(50) values of 70 and 45 nM, respectively. SCH 79797 inhibited [(3)H]haTRAP binding in a competitive manner. SCH 79797 and SCH 203099 inhibited alpha-thrombin- and haTRAP-induced aggregation of human platelets, but did not inhibit human platelet aggregation induced by the tethered ligand agonist for protease-activated receptor-4 (PAR-4), gamma-thrombin, ADP, or collagen. SCH 203099 inhibited surface expression of P-selectin induced by haTRAP and thrombin, and it did not increase P-selectin expression or prevent thrombin cleavage of the receptor. Thrombin and TFLLRNPNDK-NH(2) (TK), a PAR-1-selective agonist, produced transient increases in cytosolic free Ca(2+) concentration ([Ca(2+)](i)) in hCASMC. This increase in [Ca(2+)](i) was inhibited effectively by SCH 79797. However, the Ca(2+) transients induced by SLIGKV-NH(2,) a PAR-2-selective agonist, were not inhibited by SCH 79797. Thrombin- and TK-stimulated [(3)H]thymidine incorporation also was inhibited completely by SCH 79797. The results of this study demonstrate that SCH 79797 and SCH 203099 are potent, selective antagonists of PAR-1 in human platelets and hCASMC. These data also suggest that the thrombin stimulation of Ca(2+) transients and mitogenesis in hCASMC is mediated primarily through activation of PAR-1.

Apoptosis Regulatory Proteins↗
PubMed2000

Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation.

Twenty-six transplanted thalassemic patients out of 295 analyzed, showed the presence of persistent mixed chimerism, over a period of time varying between 2 and 11 years after BMT. Despite the presence of large numbers of residual host cells, these transplanted thalassemic patients no longer require red blood cell transfusions and have a functional graft, producing sufficient levels of hemoglobin A ranging from 8.3-14.7 g/dl. These ex-thalassemic patients with persistent mixed chimerism, although they did not achieve complete donor engraftment are no longer exposed to the risk of graft rejection. The mechanisms underlying this apparent state of tolerance or education in these patients are at the present time unknown. However, these observations may be useful for physicians involved in defining optimal strategies for clinical gene therapy, in utero hematopoietic stem cell transplantation and adoption of less toxic conditioning regimens in mini-transplantation.

Bone Marrow Transplantation↗
PubMed1999

Coexistence of two functioning T-cell repertoires in healthy ex-thalassemics bearing a persistent mixed chimerism years after bone marrow transplantation.

Bone marrow transplantation (BMT) from an HLA-identical donor is an established therapy to cure homozygous beta-thalassemia. Approximately 10% of thalassemic patients developed a persistent mixed chimerism (PMC) after BMT characterized by stable coexistence of host and donor cells in all hematopoietic compartments. Interestingly, in the erythrocytic lineage, close to normal levels of hemoglobin can be observed in the absence of complete donor engraftment. In the lymphocytic lineage, the striking feature is the coexistence of immune cells. This implies a state of tolerance or anergy, raising the issue of immunocompetence of the host. To understand the state of the T cells in PMC, repertoire analysis and functional studies were performed on cells from 3 ex-thalassemics. Repertoire analysis showed a profound skewing. This was due to an expansion of some T cells and not to a collapse of the repertoire, because phytohemagglutinin stimulation showed the presence of a complex repertoire. The immunocompetence of the chimeric immune systems was further established by showing responses to alloantigens and recall antigens in vitro. Both host and donor lymphocytes were observed in the cultures. These data suggest that the expanded T cells play a role in specific tolerance while allowing a normal immune status in these patients.

Adolescent↗
PubMed1999

Structure-activity relationships of pyrroloquinazolines as thrombin receptor antagonists.

A series of pyrroloquinazolines has been discovered that represent novel small molecule inhibitors of the intramolecular ligand of the thrombin receptor. Analogs were prepared to study the structure-activity relationships of substitution at the N 1, N3, and N7 positions of the heterocycle. Compounds 4e and 4f have been identified with IC50's of 56 and 52 nM, respectively.

Drug Evaluation, Preclinical↗
PubMed1997

Potent tetracyclic guanine inhibitors of PDE1 and PDE5 cyclic guanosine monophosphate phosphodiesterases with oral antihypertensive activity.

Tetracyclic guanines have been shown to be potent and selective inhibitors of the cGMP-hydrolyzing enzymes PDE1 and PDE5. In general, these compounds are inactive or only weakly active as inhibitors of PDE3, which is a major isozyme involved in cAMP hydrolysis. Structure-activity relationships are developed at N-1, C-2, N-3, and N-5 on the core nucleus. Compound 31, with an IC50 of 70 pM, is the most potent inhibitor of PDE1, while 50, with an IC50 of 4 nM, is the most potent inhibitor of PDE5. Compounds 20, 22, 30, and 50 are potent dual inhibitors with IC50 values below 30 nM for both PDE1 and PDE5. Compounds 12, 20, and 28 reduced blood pressure by more than 45 mmHg when administered orally at 10 mg/kg to the spontaneously hypertensive rat (SHR).

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1997

An unusual DRB1*1503 haplotype without a detectable DRB5 locus in a black African family.

A DRB1*1503 allele not associated with DRB5 locus has been detected in an African family during routine HLA typing for bone marrow transplantation. PCR/SSOP analysis showed the DR2-associated alleles in all the family members but the DRB5 locus appeared to be absent in the patient and his brother. The samples were then analyzed for the presence of DRB6 pseudogenes and we found that the unusual haplotype was associated with DRB6*0101 allele. This finding strengthen the hypothesis of a recombination hot spot between DRB1 and DRB6 genes.

Adult↗
PubMed1997

Prognostic role of cyclin D1 in non small cell lung cancer: an immunohistochemical analysis.

Lung cancer is a worldwide problem and in many countires it is the most lethal malignancy. Because relapse is frequent after resection of non small cell lung cancer, an urgent need exists to define prognostic factors which could help in choosing the best therapeutic approach. We performed immunohistochemistry on 60 formalin-fixed paraffin-embedded non small cell lung cancer specimens in order to evaluate the frequency of cyclin D1 overexpression, and to relate it to the degree of malignancy of these tumors and to the overall survival time of the patients. All specimens were positive for cyclin D1 immunostaining. We found cyclin D1 overexpression in 30 (50%) of our specimens, with no significant difference among the different histological types. Cyclin D1 overexpression correlates in a statistical manner with short-term patient survival. Mantel-Cox analysis of these data generated a significant P value = 0.003. The mean survival time and the five-year survival rate also differed statistically. We did not find any statistically significant correlation between cyclin D1 overexpression and histological grading, tumor stage or TNM status. We concluded that cyclin D1 overexpression in 30 patients is a frequent event in non small cell lung cancer pathogenesis and may have prognostic relevance.

Biomarkers, Tumor↗
PubMed1996

Dendrimer-supported combinatorial chemistry.

A new methodology for the construction of combinatorial libraries is described. The approach, termed dendrimer-supported combinatorial chemistry (DCC), centers on the use of dendrimers as soluble supports. Salient features of DCC include solution phase chemistry, homogeneous purification, routine characterization of intermediates, and high support loadings. To demonstrate the feasibility of DCC, single compounds and a small combinatorial library were prepared via the Fischer indole synthesis. Excellent product yields and purities were obtained, and dendrimer-protected intermediates could be routinely analyzed by 1H and 13C NMR and by mass spectrometry. The results indicate that DCC is a general and efficient strategy for the generation of combinatorial libraries.

Journal Article↗
PubMed1996

Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia.

Molecular genetic techniques permit sensitive assessment of host hematopoiesis after marrow transplantation for thalassemia. Information on this persistence and the cell lines in which it occurs may permit therapeutic intervention in patients at high risk for rejection and/or relapse. The objective of this study, therefore, was to determine the evolution and cell line distribution of persistent mixed chimerism detected in 55 patients treated for beta thalassemia. Our findings indicated that rejection occurred in 20 patients, the host component disappeared in 20, and mixed chimerism without transfusion need persisted for 1 to 7 years in 15. In three patients with stable mixed chimerism for 4, 5, and 7 years, host hematopoiesis fluctuated between 25% and 75%. Despite this, donor pattern beta-globin chain synthesis maintained hemoglobin levels between 10 and 13.5 g/dL without transfusion. In these three patients, the polymerase chain reaction of the VNTR and the fluorescent in situ hybridization analysis revealed the coexistence of donor and host cells in the different peripheral blood cell subpopulations and precursors studied (CD2+, CD4+, CD8+, and CD19+ granulocytes; glycophorin-A+, erythroid burst-forming units, CD33+, granulocyte-macrophage colony-forming units). We found that rejection and disease recurrence occur in approximately one third of patients with early mixed chimerism. High levels of host type hematopoiesis can be present in patients not requiring transfusion.

Adolescent↗
PubMed1996

Marrow transplantation for patients with thalassemia: results in class 3 patients.

Thalassemia patients can be categorized as class 1 (minimal liver damage and iron overload), class 3 (extensive liver damage from iron overload), and class 2 (intermediate). These categories are prognostic for treatment outcome after marrow transplantation. Class 3 patients have more transplant-related mortality than other patients. This study examines transplantation outcome for class 3 patients. Records were reviewed of 215 patients in class 3 who received transplants in Pesaro from HLA-identical related donors between May 1, 1984 and May 1, 1994. The influence of pretransplant, peritransplant, and posttransplant variables on survival, relapse, and transplant-related mortality was examined by product-limit and proportional-hazards multivariate analysis. Age and conditioning regimen were influential on survival, and regimens with less than 200 mg/kg cyclosporine (CY) were associated with 5-year survival probabilities of .74 and .63 patients younger than 17 years and older patients, respectively. Transfusion history and regimen were influential on rejection with 5 year probabilities of .53 and .24 in patients who received less than or greater than 100 red blood cell transfusions before transplantation and regimens containing less than 200 mg/kg CY. Results of transplantation for patients with advanced thalassemia treatment have improved with the introduction of conditioning regimens with less CY. This has been associated with an increase in rejection (particularly in patients who have received < 100 red blood cell transfusions before transplant). Efforts at reducing the rejection rate by modifying the conditioning regimen should be concentrated on younger patients who have received a small number of transfusions. Patients with thalassemia who have HLA-identical family members should be transplanted before they are in class 3.

Adolescent↗
PubMed1995

Recent kala-azar cases in India: isozyme profiles of Leishmania parasites.

In this study, three WHO recommended reference strains of Leishmania donovani (DD8), L. tropica (K27) and L. major (5 ASKH) were compared by isozyme analysis of 9 soluble enzymes using cellulose acetate electrophoresis (CAE). The isozyme profile of the three species showed distinct electrophoretic mobilities of the enzymes studied. This technique was applied to study the enzyme patterns of 8 clinical isolates of visceral leishmaniasis (VL) and two post kala-azar dermal leishmaniasis (PKDL) collected from the present epidemic (1990s to date). They were seen to be similar to the two isolates of the 1970s epidemic. Interspecies differences were observed in different reference Leishmania species whereas no intraspecies difference was observed amongst the clinical isolates (8VL + 2PKDL) and all of these were found to be similar to L. donovani isolates of 1970s epidemic.

Animals↗
PubMed1992

Mixed chimerism in thalassemic patients after bone marrow transplantation.

Seventy-four patients with homozygous beta-thalassemia who underwent allogeneic bone marrow transplantation (BMT) were analysed in order to evaluate the incidence and the significance of mixed chimerism (MC). Using a panel of four single locus specific minisatellite DNA probes, MC was found in 36.5%, 34.7% and 16.7% of the patients at 2, 6 and 12 months respectively after BMT. Moreover we found that different pretransplant conditioning regimens could be responsible for variations in the incidence of MC. The level of residual host cells found 2 months after BMT correlated with the occurrence of rejection.

Adolescent↗