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Biomedical subjects

M Mandel

Publications and source records attributed to M Mandel.

At least 37 records · Page 2Linked to original sources
PubMed2000

Effects of photodynamic therapy with hypericin in mice bearing highly invasive solid tumors.

The tumoricidal properties of photodynamic therapy (PDT) with hypericin (HY) were evaluated in a highly metastatic adenocarcinoma (DA3Hi) and anaplastic squamous cell carcinoma (SQ2) tumors in vivo. Photosensitization of the tumor site with hypericin (HY-PDT) reduced primary tumor development and significantly prolonged the survival of tumor-bearing (TB) mice. Of these two tumors the squamous cell carcinoma emerged as more sensitive to HY-PDT compared with DA3Hi adenocarcinoma both in vitro and in vivo. HY-PDT caused extensive tumor necrosis that was followed by local, intratumoral, and systemic inflammatory reactions. Analyses of cytokine mRNA profiles reveal increases in mRNA levels of expression confined to inflammation-related cytokines both within the tumor and also systemically (measured in spleens). However, there was no evidence for any HY-PDT-induced antitumoral immune reactions. Our results suggest that PDT with hypericin can be considered as a supplementary treatment in the management of some invasive and metastatic cancers such as squamous carcinoma and similar tumors.

Adenocarcinoma↗
PubMed1999

Design, synthesis, and biological evaluation of matrix metalloproteinase inhibitors derived from a modified proline scaffold.

The synthesis and structure-activity relationship (SAR) studies of a series of proline-based matrix metalloproteinase inhibitors are described. The data reveal a remarkable potency enhancement in those compounds that contain an sp(2) center at the C-4 carbon of the ring relative to similar, saturated compounds. This effect was noted in compounds that contained a functionalized oxime moiety or an exomethylene at C-4, and the potencies were typically <10 nM for MMP-3 and <100 nM for MMP-1. Comparisons were then made against compounds with similar functionality where the C-4 carbon was reduced to sp(3) hybridization and the effect was typically an order of magnitude loss in potency. A comparison of compounds 14 and 34 exemplifies this observation. An X-ray structure was obtained for a stromelysin-inhibitor complex which provided insights into the SAR and selectivity trends observed within the series. In vitro intestinal permeability data for many compounds was also accumulated.

Animals↗
PubMed1999

Coexistence of several unbalanced translocations in a case of neuroblastoma: the contribution of multicolor spectral karyotyping.

Spectral karyotyping (SKY) is based on the simultaneous hybridization of a set of 24 chromosome-specific DNA painting probes, each labeled with a different fluor combination. Automatic classification, based on the measurement of the spectrum for each chromosome, was applied to metaphases obtained from the affected bone marrow of a neuroblastoma case. Spectral karyotyping allowed the identification of chromosomal aberrations that could not be identified by the use of the G-banding technique, and revealed a number of gains and unbalanced translocations.

Child, Preschool↗
PubMed1999

A photodynamic pathway to apoptosis and necrosis induced by dimethyl tetrahydroxyhelianthrone and hypericin in leukaemic cells: possible relevance to photodynamic therapy.

The mechanism of cell death induction by dimethyl tetrahydroxyhelianthrone (DTHe), a new second-generation photodynamic sensitizer, is analysed in human leukaemic cell lines in comparison with the structurally related hypericin. DTHe has a broad range of light spectrum absorption that enables effective utilization of polychromatic light. Photosensitization of HL-60 cells with low doses of DTHe (0.65 microM DTHe and 7.2 J cm(-2) light energy) induced rapid apoptosis of > or =90% of the cells. At doses > or =2 microM, dying cells assumed morphological necrosis with perinucleolar condensation of chromatin in HL-60 and K-562 cell lines. Although nuclear fragmentation that is characteristic to apoptosis was prevented, DNA digestion to oligonucleosomes proceeded unhindered. Such incomplete apoptosis was more prevalent with the related analogue hypericin throughout most doses of photosensitization. Despite hypericin being a stronger photosensitizer, DTHe exhibited advantageous phototoxic properties to tumour cells, initiating apoptosis at concentrations about threefold lower than hypericin. Photosensitization of the cells induced dissociation of the nuclear envelope, releasing lamins into the cytosol. DTHe also differed from hypericin in effects exerted on the nuclear lamina, causing release of an 86-kDa lamin protein into the cytosol that was unique to DTHe. Within the nucleus, nuclear envelope lamin B underwent covalent polymerization, which did not affect apoptotic nuclear fragmentation at low doses of DTHe. At higher doses, polymerization may have been extensive enough to prevent nuclear collapse. Hut-78, CD4+ cells were resistant to the photodynamically activated apoptotic pathway. Beyond the tolerated levels of photodynamic damage, these cells died exclusively via necrosis. Hut-78 cells overexpress Bcl-X(L) as well as a truncated Bcl-X(L)tr isoform that could contribute to the observed resistance to apoptosis.

Anthracenes↗
PubMed1999

Successful human umbilical cord blood stem cell transplantation without conditioning in severe combined immune deficiency.

A 2-month-old girl with severe combined immunodeficiency (SCID), presented with mild staphylococcal skin infection, lymphopenia, low T cell number, absence of B cells, high number of NK cells, and a negligible response to mitogens. Since her older brother died as a result of SCID 2 years earlier, cord blood was harvested from a sister born 2 1/2 years earlier, who was normal and fully matched both by serology and molecular typing. In view of her clinical condition and in spite of a high number of NK cells with normal activity, HUCBT without preparative conditioning was performed. No G-CSF was administered. Engraftment with mixed chimerism was evident 3 weeks post transplantation. There were no peritransplantation complications. Eighteen months post transplantation, the girl is in excellent condition, blood counts are normal, T cell engraftment is complete, B cell engraftment is proceeding gradually, and the mitogen stimulation tests are normal. Due to the unique nature of HUCB hematopoietic cells, engraftment without conditioning may be possible in patients with SCID with fully matched donors. This is the first HUCBT performed without conditioning.

Female↗
PubMed1998

Autoantibodies in Estonia and Sweden, populations with different responses to allergens.

BACKGROUND: There are substantial differences in immune-mediated disease prevalence between different countries and populations which cannot be explained by genetic variability. AIMS: To compare the prevalence of antinuclear (ANA), antimitochondrial, antireticulin, liver-kidney microsomal, parietal cell, thyroid microsomal and double-stranded DNA (dsDNA) antibodies among adults aged 20-44 years in two towns, i.e. in Tartu, Estonia (n = 448) and in Uppsala, Sweden (n = 532) with a low and a high prevalence of allergy. METHODS: For autoantibody detection, standard indirect immunofluorescence tests on tissue and Chritidia lucilia antigenic preparations were used (sera were diluted starting from 1:10). RESULTS: The prevalence of ANA was lower in Tartu than in Uppsala (3 vs. 10% among males and 11 vs. 16% among females; p<0.01 and p<0.1, respectively). Furthermore, dsDNA antibody-positive cases were only identified in Uppsala. The largest difference between the two populations was revealed for IgM type ANA, both among males (1 vs. 6%; p<0.02) and females (5 vs. 11%; p<0.01). In addition, the antibody titers were lower in Tartu than in Uppsala (p<0.05). The prevalence of other autoantibodies was similar in the two towns. CONCLUSIONS: The findings could support that Th2-like immune responses are commoner in Sweden than in Estonia, as previously suggested by the higher prevalence of allergy.

Adult↗
PubMed1997

Central nervous system involvement at diagnosis in a case of pediatric CD30+ anaplastic large cell lymphoma.

Central nervous system (CNS) involvement in Ki-1/CD30 lymphoma is extremely rare, in contrast to the frequent involvement in other types of pediatric non-Hodgkin's lymphoma. No mechanism has yet been proposed to explain the sparing of the blood brain barrier in Ki-1/lymphoma. We present a 2-year-old boy who was admitted to the Department of Pediatric Hemato-Oncology due to lethargy, progressive breathing difficulties, massive diffuse lymphadenopathy, hepatosplenomegaly, and ichthyosis-like skin involvement with epidermolysis. A lymph node biopsy was compatible with Ki-1/CD30 anaplastic large cell lymphoma (ALCL). Bone marrow aspirate and biopsy demonstrated reactive hyperplasia. Cytogenetic analysis displayed hyperdiploid cells with 1p(-) in most cells. Cerebrospinal fluid examination showed pleocytosis with CD30+ cells. Possible mechanisms which could enable CNS involvement in this unusual case are discussed.

Central Nervous System Neoplasms↗
PubMed1996

Vincristine treatment triggering the expression of asymptomatic Charcot-Marie-Tooth disease.

A 16-year-old male suffering from Ewing's sarcoma of the pelvis was treated with vincristine as part of his chemotherapeutic protocol. The boy was never known to suffer from any neurological problems. His father had a mild limp, attributed to prolonged "taxi driving," that was never investigated medically. The first course of treatment, which included 2 mg of vincristine, resulted in clinical improvement. However, at the same time the patient developed severe weakness of both upper and lower limbs, areflexia, and gradually a pes cavus deformity. Nerve conduction studies were suggestive of severe peripheral sensorimotor neuropathy, axonal and demyelinative. A definite diagnosis of Charcot-Marie-Tooth was confirmed by molecular analysis showing the typical duplication of 1.5 megabases at 17 p11.2. This unique manifestation of vincristine neurotoxicity is reported and discussed.

Adolescent↗
PubMed1996

In vitro proliferative advantage of bone marrow cells with tetrasomy 8 in Ewing sarcoma.

We describe a case of a 14.5-year-old boy with a clinically aggressive pelvic Ewing sarcoma. The tumor cells showed the presence of a typical t(11;22)(q24;q12) aberration and gains of chromosomes 8, 10, 14, and 21. To determine the size of the trisomy and tetrasomy 8 clones an interphase analysis by fluorescence in situ hybridization with a centromere-specific chromosome 8 probe was performed. Significant quantitative differences between metaphase and interphase data were obtained. It was shown that culturing of bone marrow cells leads to enrichment of tetrasomy 8 population that may be explained by the proliferative advantage of the tetrasomy 8 cells.

Adolescent↗
PubMed1995

Two embryonal cancers after in vitro fertilization.

BACKGROUND: In vitro fertilization is not considered to be associated with an increased rate of pediatric malignancies, and only three have been reported in the literature. Two additional rare pediatric tumors in children conceived through this technique are reported. METHODS: Two children 12 and 18 months of age, developed hepatoblastoma and clear cell sarcoma of the kidney, respectively. They were both products of uneventful pregnancies induced by in vitro fertilization. No other environmental, prenatal, or family factor was found. RESULTS: The first child died after a failed remission induction with cisplatin, doxorubicin, and vincristine, whereas the second child is alive with no evidence of disease 18 months after diagnosis and treatment according to NWTS protocol. CONCLUSIONS: A possible association between in vitro fertilization and pediatric malignancies is suggested.

Antibiotics, Antineoplastic↗
PubMed1995

Expression of a human serum albumin variant with high affinity for thyroxine.

In this study a protein expression system was used to synthesize recombinant human serum albumin containing a mutation that has been shown to result in familial dysalbuminemic hyperthyroxinemia. Equilibrium dialysis was used to measure the binding of this recombinant human serum albumin with thyroxine. The association constant determined for the binding of this human serum albumin variant with thyroxine was shown to be 65-fold greater than that of recombinant normal human serum albumin.

Amino Acid Sequence↗
PubMed1995

Translocation (2;14)(p13;q32) in CD10+ ;CD13+ acute lymphatic leukemia.

The rare t(2;14)(p13;q32) was previously described in the three pediatric patients with acute lymphatic leukemia. In these cases this abnormality was found at diagnosis, manifested the sole chromosomal abnormality, and was associated with a favorable prognosis. We here describe three cases of leukemia where such translocations were found at relapse, were associated in two of the cases with additional known characteristic chromosomal aberration, and were associated with a grave prognosis. Interestingly enough, the malignant cells of all three patients shared the same surface antigens: CD34, HLA DR, CD10, CD20, and the myeloid marker CD13. The leukemic clone exhibiting t(2;14) probably evolved from a t(1;19)6q- pre-B acute lymphatic leukemia in one of the cases, and from a chronic phase Ph1 chromosome in another. The significance of the translocation and the coexistence of CD10 and CD13 on the same cell are discussed.

Adolescent↗
PubMed1995

Detection of mutagen specific adduct formation in DNA using sequencing methodology.

It has been reported that single stranded viral DNA reacts with the carcinogen, chloroacetaldehyde at specific hot spots (Premaratne et al., 1993 Int. J. Biochem. 25, 1669-1672). We tested this occurrence with several other mutagens and potential carcinogens. A series of chemicals (chloroacetaldehyde, methyl, ethyl, and propyl nitro nitrosoguanidine, hydrazine, 2,4 dinitrophenyl hydrazine, hydroxylamine and methyl methanesulfonate) were each separately reacted with viral M13mp18 DNA for 2 hr at 37 degrees C and pH 4.9. The locations of adduction were identified as points of chain termination (or polymerase fall off) when the reacted DNA was subjected to a modified sequencing procedure that had ample regular labeled and unlabeled nucleotides but lacked dideoxy chain termination mixtures. Chain termination was observed to occur at specific, non-random, sites rather than with equal probability at all bases of the DNA. Chemicals with similar structures had identical points of "fall off". The pattern of chain termination appears to be unique to each class of compounds and is independent of temperature, pH, and salt concentration. Termination is believed to occur when the DNA polymerase encounters an adduct. Mutagens of different unrelated structures when reacted with this DNA produced different sites of adduct formation, while the alkyl nitro nitrosoguanidines, compounds with homologous structure showed identical points of chain termination.

Animals↗