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Biomedical subjects

D Ma

Publications and source records attributed to D Ma.

At least 235 records · Page 13Linked to original sources
PubMed1994

Response of calcitonin-gene-related peptide-like immunoreactive nerve fibers of the anterior pituitary to adrenalectomy in the rat.

The mammalian anterior pituitary is known to be regulated by humoral factors only, no direct neural influence having ever been discovered. Our recent studies have shown in several species that there are substantial amounts of substance P and calcitonin-gene-related peptide-like immunoreactive (CGRP-LI) nerve fibers in the anterior pituitary and that they can make synaptic contacts with secretory cells, among which corticotropes. In the present study, we investigated changes in CGRP-LI nerve fibers of the anterior pituitary after bilateral adrenalectomy in the rat. The results show that the number of CGRP-LI nerve fibers increases significantly. In parallel, they cover a wider area of the gland after the operation, suggesting a direct neural influence.

Adrenalectomy↗
PubMed1994

Histocytochemistry of glycoconjugates in nasal inverted papilloma.

In order to investigate the changes in cellular distribution of the glycocalyces in nasal inverted papilloma, formalin-fixed, paraffin-embedded biopsy specimens of inverted papilloma were analyzed by the avidin-biotin-peroxidase complex technique for the demonstration of peanut agglutinin (PNA) receptors, concanavalin A (Canavalia ensiformis agglutinin; ConA) receptors, carcinoembryonic antigen (CEA), and keratin, and compared with normal nasal mucosa, nasal polyps, and papillary adenocarcinoma. The inverted papillomas were positive for PNA and CEA, to the same degree as papillary adenocarcinoma. Their PNA binding was related to the degree of dysplasia. The ConA reaction was intermediate between that of normal mucosa and adenocarcinoma. The results suggest that the alteration of cellular glycoprotein structure in inverted papilloma is associated with its biologic characterization.

Adult↗
PubMed1994

Rejection of intraocular tumors from transgenic mice by tumor-infiltrating lymphocytes.

The present study examined the role of tumor infiltrating lymphocytes (TIL) in the rejection of intraocular tumors from SV40 transgenic mice. Tumor cells from an intraocular tumor arising in an SV40 transgenic FVB/N mouse were transplanted into the eyes of syngeneic FVB/N mice and the TIL isolated. TIL were assessed for direct cytolytic activity in vitro. TIL were also transferred passively to immunosuppressed FVB/N mice to determine if they could mediate intraocular tumor rejection. The role of CD4+ and CD8+ T cells in intraocular tumor rejection was evaluated by depleting the respective cell populations in FVB/N hosts prior to intraocular tumor challenge. The results showed that intraocular tumors undergoing rejection in immunocompetent syngeneic hosts became infiltrated with T cells, with the CD8+ subset predominating at the time of rejection. By contrast, athymic nude mice did not reject the intraocular tumors nor did the tumors become infiltrated with TIL. TIL displayed direct, tumor-specific cytolytic activity immediately after isolation from the tumor-containing eyes. FVB/N hosts depleted of CD4+ T cells were unable to reject their intraocular tumors. In vivo depletion of CD8+ T cells delayed, but did not prevent tumor rejection. Adoptively transferred TIL mediated swift rejection of intraocular tumors in immunoincompetent recipients. Recipients of TIL, but not recipients of normal spleen cells, acquired significant tumor-specific CTL activity that was demonstrable in vitro. The results strongly suggest, but do not prove, that TIL mediate rejection of intraocular tumors from transgenic mice by direct cytolysis. Although CD4+ T cells are necessary for tumor rejection and are capable of direct cytolysis, the predominant effector cells are CD8+ CTL.

Animals↗
PubMed1994

The influence of induction chemotherapy dose and dose intensity on the duration of remission in acute myeloid leukemia. Australian Leukemia Study Group.

The aim of this study was to assess the influence of dose and dose intensity (DI) of induction and consolidation chemotherapy on relapse rates in 264 de novo patients with acute nonlymphocytic leukemia (ANLL). Patients were randomised to receive cytosine arabinoside (ARAC) 100 mg/m2 continuous infusion for 7 days and daunorubicin (DNR) 50 mg/m2 IV day 1-3 (7-3) or the same drugs with the addition of etoposide 75 mg/m2 IV days 1-7 (7-3-7). Cox proportional hazards regression models were used throughout to identify prognostic factors, including dose delivery parameters, influencing the rate of relapse. Of 152 patients who achieved a complete remission (CR), 104 have relapsed with a median duration of CR of 15.8 months. Actual dose delivered was prospectively documented. Cox regression analysis identified the most significant prognostic factors jointly influencing duration of CR as performance status groups (p < 0.0001), percentage peripheral blasts (p = 0.0015), 7-3-7 arm (p = 0.0075), age < 40 years (p = 0.022) and induction dose ARA-C plus DNR (p = 0.029). In this analysis patients randomized to the 7-3-7 arm had an estimated 43% reduction in the relapse rate and each 10% reduction of doses ARA-C and DNR was associated with an estimated 45% increase in the relapse rate. The number of induction courses, delays in treatment and induction dose intensity did not significantly influence the duration of CR nor did any of the consolidation treatment parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Distribution, content and action site of leucine-enkephalin in pulmonary artery wall of rat and rabbit].

Using immunohistochemical method to investigate the distribution of peptidergic fibers in the pulmonary artery wall of SD rat, L-enkephalin immunoreactive (L-ENK ir) fibers were easily demonstrated. The contents of L-ENK in pulmonary artery of rat and rabbit measured by radioimmunoassay were respectively 439.18 +/- 30.52 and 29.9 +/- 1.4 (pg/mg of wct tissue). Contraction of superfused strips of pulmonary artery of rabbit could be evoked by parameter I electric field stimulation. The response was blocked by alpha-receptor antagonist phentolamine. Alpha 2-receptor antagonist Yohimbine enhanced the response in small doses (0.06-0.12 mumol/L), while inhibited in large (3.2 mumol/L). The contraction could also be enhanced when the artery strips were preincubated with naloxone. After the alpha-receptors were blocked with phentolamine, stronger contraction could still be evoked by parameter II electric field stimulation and the response was not affected by naloxone. L-ENK had no effect on the contraction evoked by exogenous NE. The present experiments demonstrate that enkephalin presented in the pulmonary artery wall are released by electric field stimulation. Enkephalin may reduce the release of NE from sympathetic nerve endings via opioid receptors and inhibit the contraction response.

Animals↗
PubMed1994

Characterization of intraocular tumors arising in transgenic mice.

PURPOSE: To characterize intraocular tumors that arise by in situ transformation in the choroid-retinal pigment epithelium (RPE) in transgenic mice bearing the SV40 oncogene under the control of the mouse tyrosinase promoter. METHODS: Tumors from TySV40 transgenic mice were characterized in vivo and in vitro by immunohistology, compound microscopy, and electron microscopy. Tumor cell lines were established and characterized for growth and metastatic potential in the eyes of nude mice. RESULTS: On light microscopy, ocular tumors were predominantly epithelioid, although occasional clusters of spindle cells were also present. Transmission electron microscopy revealed the presence of numerous basal infoldings and abundant multilaminated basement membranes on the ocular tumors. Tumors stained with antibodies to melanoma-associated antigens, gangliosides GD2 and GD3, and the SV40 T antigen. Radiolabeled transgenic tumor cells preferentially localized in the liver after intravenous injection in normal mice. Intracamerally transplanted transgenic tumors metastasized from the eyes to the livers of nude mice. CONCLUSIONS: In TySV40 transgenic mice, intraocular tumors develop that arise at the choroid-RPE interface, and they display morphologic and ultrastructural features consistent with RPE carcinomas. However, the transgenic tumors express melanoma-associated antigens and a propensity to metastasize to the liver, two features characteristic of uveal melanomas. The TySV40 transgenic murine tumors represent potentially useful tools for investigations into the biology and metastasis of intraocular neoplasms.

Animals↗
PubMed1993

Chemistry, binding affinities, and behavioral properties of a new class of "antineophobic" mitochondrial DBI receptor complex (mDRC) ligands.

The mitochondrial DBI receptor complex (mDRC; previously called the peripheral benzodiazepine receptors) is linked to the production of neurosteroids such as pregnenolone sulfate, dehydroepiandrosterone sulfate, and others. In order to gain further information as to the function of the mDRC in the brain, we have constructed and tested both in vitro and in vivo a novel series of ligands, 2-arylindole-3-acetamides. The SAR studies detailed herein delineate some of the structural features required for high affinity binding to the mDRCs. In most cases the new ligands were prepared by use of the Fischer indole synthesis. Variations in the length and number of the alkyl groups on the amide nitrogen were probed together with the effects of halogen substituents on one or both of the aryl rings. Some ligands were also synthesized for study which represent conformationally constrained versions of the parent structure. Broad screening studies revealed these indoleacetamides to be highly selective for the mDRC, since they failed to bind with any significant affinity to other receptor systems. Some of the ligands were found to exhibit Ki values in the low nanomolar range for the mDRC as measured by the displacement of [3H]4'-chlorodiazepam. A subset of these ligands was also shown to stimulate pregnenolone formation from the mitochondria of C6-2B glioma cells with an EC50 of about 3 nM. In animal experiments ligands selected for further study were found to exhibit antineophobic effects, in spite of the fact that they exhibit no direct action on GABAA receptors. Consequently, it is postulated that these ligands owe their action to an indirect modulation of GABAA receptor function, presumably by stimulation of neurosteroid production and release from glial cells, followed by neurosteroid modulation of GABA's action on the chloride ion channel conductance of GABAA receptors.

Acetamides↗
PubMed1993

Calcitonin gene-related peptide- and substance P-like-immunoreactive innervation of the anterior pituitary in the rat.

In our previous studies substantial amounts of substance P- and calcitonin gene-related peptide-like-immunoreactive nerve fibers have been identified in the anterior pituitary of the monkey and the dog. They were found to be in close proximity to the gland cells, even making synaptic contacts with some types of the gland cells. The present study investigated in detail the calcitonin gene-related peptide- and substance P-like immunoreactivities of the anterior pituitary in the rat. Though the immunoreactive fibers were not as abundant as in the anterior pituitary of the monkey and the dog, they still appeared in notable amounts. The calcitonin gene-related peptide- and substance P-like-immunoreactive nerve fibers occurred mostly as thin, tortuous, and densely varicose fibers, weaving among the gland cells. They are widely distributed, more in the central part of the gland. Double-immunostaining proved nearly complete co-localization of these two peptides in the nerve fibers. It is hypothesized that the anterior pituitary can be regulated by direct neural factors as well as humoral factors.

Animals↗
PubMed1993

Analysis of lectin receptors in normal nasal mucosa, nasal polyp, inverted papilloma and papillary adenocarcinoma.

In order to investigate the changes in glycoprotein structure in the process of cellular differentiation of the nasal mucosa, formalin-fixed, paraffin-embedded biopsy specimens of normal nasal mucosae, nasal polyps, inverted papillomas and papillary adenocarcinomas were analysed by the Avidin Biotin-Peroxidase Complex technique for the demonstration of peanut agglutinin (PNA) receptors, concanavalin ensifomis agglutinin (ConA) receptors, ulex europeaus agglutinin (UEA-I) receptors, wheat germ agglutinin (WGA) receptors, carcino-embryonic antigen (CEA) and keratin. The quantity and distribution of PNA receptors, ConA receptors, UEA-I receptors and CEA were different, in relation to the varying pathological changes. The results suggest that the glycoprotein structure in the cells of the nasal mucosa will change following their differentiation and malignant transformation, which may be helpful in establishing the diagnosis.

Adenocarcinoma, Papillary↗
PubMed1993

Regulation of carotenoid and bacteriochlorophyll biosynthesis genes and identification of an evolutionarily conserved gene required for bacteriochlorophyll accumulation.

The temporal expression of ten clustered genes required for carotenoid (crt) and bacteriochlorophyll (bch) biosynthesis was examined during the transition from aerobic respiration to anaerobiosis requisite for the development of the photosynthetic membrane in the bacterium Rhodobacter capsulatus. Accumulation of crtA, crtC, crtD, crtE, crtF, crtK, bchC and bchD mRNAs increased transiently and coordinately, up to 12-fold following removal of oxygen from the growth medium, paralleling increases in mRNAs encoding pigment-binding polypeptides of the photosynthetic apparatus. The crtB and crtI genes, in contrast, were expressed similarly in the presence or absence of oxygen. The regulation patterns of promoters for the crtA and crtI genes and the bchCXYZ operon were characterized using lacZ transcriptional fusion and qualitatively reflected the corresponding mRNA accumulation patterns. We also report that the bchI gene product, encoded by a DNA sequence previously considered to be a portion of crtA, shares 49% sequence identity with the nuclear-encoded Arabidopsis thaliana Cs chloroplast protein required for normal pigmentation in plants.

Aerobiosis↗
PubMed1993

Isolation of a cDNA encoding the largest subunit of TFIIA reveals functions important for activated transcription.

Transcription factor IIA has been shown to interact with the TATA-binding protein and to act early during preinitiation complex formation. The human factor is composed of three subunits (alpha, beta, gamma). A human cDNA clone encoding the largest subunit of TFIIA (alpha) was isolated. The recombinant alpha polypeptide, together with the beta and gamma subunits, was capable of reconstituting TFIIA activity. Studies using antibodies raised against recombinant alpha polypeptide demonstrate that TFIIA can be an integral component of the preinitiation complex. We demonstrate that TFIIA not only interacts with TBP but also can associate with the TFIID complex. Functional assays establish that TFIIA has no apparent role in basal transcription but plays an important role in activation of transcription. Interestingly, amino acid sequence analyses of the beta-subunit demonstrate these residues to be entirely contained within the carboxyl terminus of the cDNA clone encoding the alpha-subunit.

Amino Acid Sequence↗
PubMed1993

Molecular cloning and characterization of acrA and acrE genes of Escherichia coli.

The DNA fragment containing the acrA locus of the Escherichia coli chromosome has been cloned by using a complementation test. The nucleotide sequence indicates the presence of two open reading frames (ORFs). Sequence analysis suggests that the first ORF encodes a 397-residue lipoprotein with a 24-amino-acid signal peptide at its N terminus. One inactive allele of acrA from strain N43 was shown to contain an IS2 element inserted into this ORF. Therefore, this ORF was designated acrA. The second downstream ORF is predicted to encode a transmembrane protein of 1,049 amino acids and is named acrE. Genes acrA and acrE are probably located on the same operon, and both of their products are likely to affect drug susceptibilities observed in wild-type cells. The cellular localizations of these polypeptides have been analyzed by making acrA::TnphoA and acrE::TnphoA fusion proteins. Interestingly, AcrA and AcrE share 65 and 77% amino acid identity with two other E. coli polypeptides, EnvC and EnvD, respectively. Drug susceptibilities in one acrA mutant (N43) and one envCD mutant (PM61) have been determined and compared. Finally, the possible functions of these proteins are discussed.

Acriflavine↗
PubMed1993

Analysis of the promoter and regulatory sequences of an oxygen-regulated bch operon in Rhodobacter capsulatus by site-directed mutagenesis.

The biosynthesis of pigments (carotenoids and bacteriochlorophylls) in the photosynthetic bacterium Rhodobacter capsulatus is regulated by the oxygen concentration in the environment. However, the mechanism of this regulation has remained obscure. In this study, transcriptional fusions of the bchCXYZ promoter region to lacZ were used to identify the promoter and regulatory sequences governing transcription of these bacteriochlorophyll biosynthesis genes. The promoter region was identified in vivo by making deletions and site-directed mutations. The 50 bp upstream of the promoter region was shown to be required for the oxygen-dependent transcriptional regulation of bchCXYZ. A previously described palindrome sequence is also likely involved in the regulation. A gel mobility shift assay further defined the interaction of transcription regulators with these DNA sequence elements in vitro and demonstrated that a DNA-protein complex is formed at this promoter region. Since the suggested promoter sequence and the palindrome sequence are found upstream of several other bch and crt operons, these sequences may be responsible for regulating oxygen-dependent pigment biosynthesis at the level of transcription in R. capsulatus. In addition, these cis-acting DNA elements are not found upstream of puh and puf operons, which encode the structural polypeptides of the reaction center and light-harvesting I complexes. This observation supports the model of different regulatory mechanism for the pigment biosynthesis enzymes and structural polypeptides required for the production of the photosynthetic apparatus.

Bacteriochlorophylls↗
PubMed1993

Participation of mitochondrial diazepam binding inhibitor receptors in the anticonflict, antineophobic and anticonvulsant action of 2-aryl-3-indoleacetamide and imidazopyridine derivatives.

The 2-hexyl-indoleacetamide derivative, FGIN-1-27 [N,N-di-n-hexyl-2- (4-fluorophenyl)indole-3-acetamide], and the imidazopyridine derivative, alpidem, both bind with high affinity to glial mitochondrial diazepam binding inhibitor receptors (MDR) and increase mitochondrial steroidogenesis. Although FGIN-1-27 is selective for the MDR, alpidem also binds to the allosteric modulatory site of the gamma-aminobutyric acidA receptor where the benzodiazepines bind. FGIN-1-27 and alpidem, like the neurosteroid 3 alpha,21-dehydroxy-5 alpha-pregnane-20-one (THDOC), clonazepam and zolpidem (the direct allosteric modulators of gamma-aminobutyric acidA receptors) delay the onset of isoniazid and metrazol-induced convulsions. The anti-isoniazid convulsant action of FGIN-1-27 and alpidem, but not that of THDOC, is blocked by PK 11195. In contrast, flumazenil blocked completely the anticonvulsant action of clonazepam and zolpidem and partially blocked that of alpidem, but it did not affect the anticonvulsant action of THDOC and FGIN-1-27. Alpidem, like clonazepam, zolpidem and diazepam, but not THDOC or FGIN-1-27, delay the onset of bicuculline-induced convulsions. In two animal models of anxiety, the neophobic behavior in the elevated plus maze test and the conflict-punishment behavior in the Vogel conflict test, THDOC and FGIN-1-27 elicited anxiolytic-like effects in a manner that is flumazenil insensitive, whereas alpidem elicited a similar anxiolytic effect, but is partially blocked by flumazenil. Whereas PK 11195 blocked the effect of FGIN-1-27 and partially blocked alpidem, it did not affect THDOC in both animal models of anxiety.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggression↗
PubMed1993

[The study on prethrombotic state in patients with chronic obstructive pulmonary disease and cor pulmonale].

We measured PT, TT, KPTT, Fg, vWF, AT-IIIAg, AT-IIIA, alpha 2M, TXB2, 6-keto-PGF1 alpha, PLg, tPAAg, tPAA and PAI of patients with acute onset of chronic bronchitis, pulmonary emphysema, and cor pulmonale. The results were that many above parameter had a worsening tendency along with deterioration of COPD, and Fg, vWF, TXB2, 6-keto-PGF1 alpha, tPAA and PAI were more sensitive than others. The analysis of multiple liner regression of 22 blood items in patients with cor pulmonale showed that pH, PaO2, PaCO2 had correlation with many items of prethrombotic state. We consider that in the progress of COPD, prethrombotic state gradually appeared and aggravated. The causes may be related with repeatedly infections, low O2, high CO2 and imbalance of acid-base equilibrium.

Aged↗
PubMed1993

Stimulation of brain steroidogenesis by 2-aryl-indole-3-acetamide derivatives acting at the mitochondrial diazepam-binding inhibitor receptor complex.

The 2-aryl-indole-3-acetamide derivatives, 2-hexyl-indole-3-acetamide (FGIN-1-27) and 2-hexyl-indole-3-acetamide-N-benzene-tricarboxylic acid (FGIN-1-44) displaced [3H]1-(2-chlorophenyl)-N-methyl-N-(1- methylpropyl)-3-isoquinoline-carboxamide([3H]PK 11195) and [3H]4-chlorodiazepam ([3H]4'CD) from binding sites located on the rat brain mitochondrial DBI receptor complex (MDRC) with Ki values in the nanomolar range. Both 2-aryl-indole-3-acetamide derivatives acted as agonists at the MDRC and thereby stimulated the rate of pregnenolone synthesis in isolated rat brain mitochondria; this effect was inhibited by PK 11195, an MDRC ligand that does not possess steroidogenic activity. FGIN-1-27 and FGIN-1-44 failed to bind to other transmitter receptors, including gamma-aminobutyric-A receptors. When administered orally to rats, both FGIN-1-27 and FGIN-1-44 reduced fear of novelty in the elevated plus maze test. This action was prevented by PK 11195, but not by flumazenil. FGIN-1-44, which was rapidly converted to FGIN-1-27 in the rat brain, was 3 to 4 times more potent than FGIN-1-27 in reducing fear of novelty because of its greater bioavailability. FGIN-1-27 increased the brain pregnenolone content in adrenalectomized-castrated rats pretreated with trilostane (in order to prevent metabolism of pregnenolone to progesterone). This increase was blocked by pretreatment with PK 11195. Although FGIN-1-27 and FGIN-1-44 increased the corticosterone concentration in adrenal glands and plasma of hypophysectomized rats in a PK 11195-sensitive manner, both drugs failed to increase adrenal steroidogenesis in sham-operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed1992

Dynamics of DNA supercoiling by transcription in Escherichia coli.

The relative rotation between RNA polymerase and DNA during transcription elongation can lead to supercoiling of the DNA template. However, the variables that influence the efficiency of supercoiling by RNA polymerase in vivo are poorly understood, despite the importance of supercoiling for DNA metabolism. We describe a model system to measure the rate of supercoiling by transcription and to estimate the rates of topoisomerase turnover in Escherichia coli. Transcription in a strain lacking topoisomerase I can lead to optimal supercoiling, wherein nearly one positive and one negative superturn are produced for each 10.4 base pairs transcribed. This rapid efficient supercoiling is observed during transcription of membrane-associated gene products, encoded by tet (the gene for tetracycline resistance) and phoA (the gene for E. coli alkaline phosphatase), when the genes are oppositely oriented. Replacement of tet by cat, the gene from Tn9 encoding resistance to chloramphenicol, whose gene product is soluble in the cytosol, reduces the efficiency of supercoiling by RNA polymerase. In a wild-type topoisomerase background, both gyrase and topoisomerase I are kinetically competent to relieve superturns produced by transcription. These results suggest that the level of DNA supercoiling in vivo is probably determined by topoisomerase activity, not by transcription.

Alkaline Phosphatase↗