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Biomedical subjects

A R Saha

Publications and source records attributed to A R Saha.

13 recordsLinked to original sources
PubMed2000

Chicken synucleins: cloning and expression in the developing embryo.

Synucleins comprise a family of small intracellular proteins that have recently attracted considerable attention because of their involvement in human diseases. Mutations of alpha-synuclein has been found in several families with hereditary early-onset Parkinson's disease and accumulation of this protein in characteristic cytoplasmic inclusions is a pathohistological hallmark of several neurodegenerative diseases that have been recently classified as 'alpha;-synucleinopathies' (reviewed in Brain Res. Bull. 50 (1999) 465; J. Neurosci. Res. 58 (1999) 120; Philos. Trans. R. Soc. Lond. Biol. Sci. 354 (1999) 1101; Brain Pathol. 9 (1999) 733). Aggregates of beta-synuclein and persyn (gamma-synuclein) also have been found in dystrophic neurites associated with Parkinson's and other neurodegenerative diseases (Proc. Natl. Acad. Sci. USA 96 (1999) 13450; and our unpublished observations). Moreover, persyn has been implicated in malignization of breast tumours (Cancer Res. 57 (1997) 759; Cancer Res. 59 (1999) 742; Hum. Mol. Genet. 7 (1998) 1417). All synucleins have distinct, although overlapping, patterns of expression in the embryonic, postnatal and adult mammalian nervous systems, suggesting important, although still not clear, biological functions in neuronal developing. Chicken embryo is a unique object for developmental studies that allows in vivo manipulations not always possible for mammalian embryos. Studies of synucleins expression in this model system could shed light on their functions in the developing nervous system. We cloned three chicken synucleins from the embryonic neural cDNA libraries and studied their expression in normal chicken embryonic tissues by Northern and in situ hybridization with specific probes. Our results demonstrate that primary structures and expression patterns of synucleins are similar in birds and mammals, suggesting that conserved function of synucleins is important for embryonic development of vertebrates.

Amino Acid Sequence↗
PubMed2000

Induction of neuronal death by alpha-synuclein.

The molecular and cellular mechanisms underlying neuronal loss in neurodegenerative diseases are unclear. It is generally thought that aggregation of mutated, abnormally modified or abnormally folded proteins leads to the accumulation of extracellular, intracellular or intranuclear deposits that severely compromise cell physiology, leading to the death of the affected neurons. However, there is growing evidence that neuronal apoptosis in the absence of obvious pathological deposits could have a serious impact on the pathogenesis of neurodegenerative diseases. alpha-Synuclein has been implicated in aetiology and pathogenesis of certain neurodegenerative diseases, although the precise role of this protein in neurodegeneration is uncertain. The normal functions of alpha-synuclein and other members of the synuclein family in the development and function of the nervous system also remain elusive. Here we show that overexpression of wild-type and mutant forms of alpha-synuclein in cultured neurons, but not the closely related persyn (gamma-synuclein), causes apoptosis. These findings suggest that abnormalities of alpha-synuclein metabolism could lead to the neuronal loss occurring in certain forms of neurodegeneration before the formation of characteristic pathological lesions.

Amino Acid Sequence↗
PubMed1995

Zinc induces thymulin secretion from human thymic epithelial cells in vitro and augments splenocyte and thymocyte responses in vivo.

Zinc is incorporated into zinc-thymulin by the thymus and in this form is a critical hormonal regulator of cellular immunity. In the absence of serum, zinc induces human thymic epithelial cells (TEC) to secrete a factor which promotes the expansion of interleukin-2 (IL-2) receptor positive human peripheral blood lymphocytes in response to a low dose of phytohemagglutinin (PHA). This factor is removed by antithymulin antisera plus filtration and is thus presumed to be zinc-thymulin. Intraperitoneal treatment of hydrocortisone treated aged mice with zinc-thymulin (100 ng/day x 5) resulted in mild augmentation of splenocyte but not thymocyte responses in vitro to IL-1, IL-2, and natural cytokine mixture (NCM) and to PHA and concanavalin A (Con A) (average increase 40%). Like zinc-thymulin treatment, oral ingestion of zinc (72 micrograms/day x 5) resulted in augmentation of splenocyte IL responses; in contrast, it augmented thymocyte responses to all stimuli (average increase 100%). These preliminary experiments indicate that treatment with zinc may have immunotherapeutic relevance, particularly in the aged and stressed organism.

Administration, Oral↗
PubMed1992

Potentiation of immune responses in mice by a new inosine derivative--methyl inosine monophosphate (MIMP).

Inosine 5'-methyl monophosphate (MIMP) is a new immunomodulator designed to improve upon the activity of other thymomimetic purines. In Balb/c mice, MIMP was assessed for toxicity and activity on immune responses. The lethal dose for half the mice (LD50) exceeded 500 mg/kg of body weight by both the parenteral and oral routes. At doses of 1-100 mg/kg, the mice showed no visible untoward effects. The antibody response of splenocytes to sheep erythrocytes (SRBC) was measured by IgM plaque-forming cells (PFC) in soft agar under optimal conditions of immunization and challenge. MIMP (1-100 mg/kg) was given by both the intraperitoneal and oral routes (gavage) at the time of SRBC injection and 4 days thereafter. The PFC response was found to be significantly augmented. The maximum effect (approximately 2x) was observed at 50 and 100 mg/kg, via intraperitoneal (i.p.) and oral routes, respectively. Increases (maximally 1.5x) in the responses of splenic lymphocytes to mitogen stimulation with phytohemagglutinin (PHA) and concanavalin A (Con A) were observed under similar conditions of MIMP treatment. SRBC-induced delayed-hypersensitivity (DTH) was also measured under optimal conditions. By both i.p. and oral routes, enhancement of DTH response was produced by the lower doses of MIMP (0.01-1 mg/kg). Again, a second peak of optimum stimulation of DTH response was produced by 50 mg/kg of MIMP when administered by both routes. The effect was observed mainly on the sensitization rather than on the expression phase. MIMP qualifies as an effective immunopotentiator in normal mice.

Adjuvants, Immunologic↗
PubMed1991

Effects of heptaminol AMP amidate on T cell populations of peripheral blood lymphocytes and splenocytes in mice.

Heptaminol AMP amidate (HAA), a nucleotide derivative increased the percentage of T cell surface phenotypes on peripheral blood lymphocytes (PBL) of mice primed with sheep red blood cells. The T cell surface phenotypes Thy1.2, Lyt1, L3T4 and Lyt2 increased on the PBL of HAA administered mice to 136, 145, 144 and 153%, respectively over those on the PBL of control mice.

Adenosine Monophosphate↗
PubMed1990

Effects of heptaminol AMP amidate (HAA) on cyclic AMP level and mitogen-induced proliferation of murine spleen cells.

Heptaminol AMP amidate (HAA), a nucleotide derivative, was found to elevate the intracellular cyclic AMP (cAMP) level of cultured mice spleen cells in a time- and dose-dependent manner. Theophylline and imidazole, when added to the spleen cell culture simultaneously with HAA, respectively caused a further rise and a fall of the cAMP level increased by HAA alone. When comparatively higher doses of the T cell mitogen concanavalin A (Con A) were used in the culture, Con A-induced cell proliferation was mildly inhibited in the culture of spleen cells pooled from HAA administered mice in comparison to the culture of spleen cells pooled from saline treated mice. On the other hand, when another T cell mitogen phytohemagglutinin P (PHA) was used in different concentrations in the culture, there was a trend of enhanced cell proliferation in the culture of spleen cells pooled from HAA administered mice in comparison to the responses in the culture of spleen cells pooled from saline treated mice. The present results supported the previous findings that HAA-mediated immunopotentiation was closely related with a cAMP level elevating property of HAA, and the compound also enhanced the function of helper T cells.

Adenosine Monophosphate↗
PubMed1990

Comparisons of heptaminol AMP amidate and dibutyryl cyclic AMP on murine splenocytes proliferation.

Hepataminol AMP amidate (HAA), a nucleotide derivative possessing immunopotentiating activities, inhibited the mitogen-induced proliferation of murine splenocytes in vitro at the higher concentrations. Concanavalin A-induced mitogenic response was inhibited to 65 and 15% of the control value by HAA at the concentrations of 10(-4) and 10(-3) M, respectively. HAA also inhibited phytohemagglutinin P and lipopolysaccharide-induced responses at the same concentrations. The pattern of inhibition of mitogen-induced responses by HAA at higher concentrations was found to be almost similar to that of dibutyryl cyclic AMP (DbcAMP). Both HAA and DbcAMP also inhibited the blastogenesis of spleen cells in one way mixed lymphocyte reaction.

Adenosine Monophosphate↗
PubMed1988

Effect of heptaminol AMP amidate, a new nucleotide derivative, on in vitro humoral immunity.

Heptaminol AMP amidate (HAA), a newly developed derivative of 5'-AMP, was found to potentiate the in vitro primary humoral immune response against T cell-dependent antigen, sheep red blood cells, when HAA was present in the early phase of spleen cell culture. Such a potentiating effect was not found against T cell-independent antigens such as lipopolysaccharide (LPS), trinitrophenylated (TNP)-LPS and TNP-Ficoll. The pattern of HAA-mediated immunopotentiation was similar to that of dibutyryl cyclic AMP. When HAA was added to the culture simultaneously with theophylline and imidazole, the immunopotentiating effect of HAA was further augmented and suppressed, respectively. The present results suggested that HAA-mediated immunopotentiation might be in some way related to the intracellular level of cyclic nucleotides in the early phase of culture.

Adenosine↗
PubMed1988

Effects of heptaminol AMP amidate on suppressor and helper function of murine T cells.

Heptaminol AMP amidate (HAA), a newly developed nucleotide derivative, was found to restore the immunosuppression in mice due to the induction of suppressor T (Ts) cells by concanavalin A (Con A) (50 micrograms/body). HAA also inhibited Con A-mediated in vitro induction of Ts cells. On the contrary, the administration of HAA in mice primed with keyhole lympet hemocyanin (KLH) (30 micrograms/body) caused an enhanced induction of antigen specific helper T (Th) cells. Effects of HAA on Ts and Th cells were found to be dependent on their level of induction. The administration of HAA also increased the spleen cell number and augmented the plaque forming cell response to some extent in cyclophosphamide treated mice. The present results suggested that HAA-mediated immunopotentiation was possible by a combined suppressive effect on Ts cells and enhancing effect on Th cells.

Adenosine Monophosphate↗
PubMed1987

Immunopotentiating activity of a nucleotide derivative, heptaminol AMP amidate (HAA) in mice and spontaneously hypertensive rats (SHR).

The immunopotentiating activity of heptaminol AMP amidate (HAA), a new derivative of 5'-AMP, was examined in experimental animals. Anti-SRBC PFC activity and antibody titer values augmented for both of single and 4 days consecutive administrations in ICR male mice. The dose of 10 mg/kg was found to cause the maximum enhancement. In spontaneously hypertensive rats, with a state of immunosuppression, 10 days consecutive administrations of HAA at the dose of 10 mg/kg was found to increase significantly the anti-SRBC PFC and antibody titer values. From these results, it is tempting to suggest that HAA may possess an immunopotentiating activity.

Adenosine Monophosphate↗
PubMed1984

Ester synthesis catalyzed by polyethylene glycol-modified lipase in benzene.

Lipoprotein lipase, which catalyzes hydrolysis of emulsified triglycerides or water-insoluble esters, was modified with 2,4-bis(o-methoxy-polyethylene glycol)-6-chloro-s-triazine(activated PEG2). The modified lipase, in which 55% of the total amino groups in the lipase molecule, was soluble in organic solvents such as benzene, toluene, chloroform and dioxane. The modified lipase could catalyze ester synthesis reaction in benzene. When very hydrophobic substrates of lauryl alcohol and stearic acid were used, the ester synthesis reaction proceeded efficiently in the transparent benzene solution with the maximum activity of approximate 5.0 mumoles/min/mg of protein. Ester exchange and aminolysis reactions were also conducted with the modified lipase in benzene.

Benzene↗