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A Segal

Publications and source records attributed to A Segal.

At least 19 recordsLinked to original sources
PubMed1979

In vitro Dimroth rearrangement of 1-(2-carboxyethyl) adenine to N6-(2-carboxyethyl)adenine in single-stranded calf thymus DNA.

The new adduct N6-(2-carboxyethyl)adenine (N6-CEA) was prepared from 1-(2-carboxyethyl)adenine (1-CEA) by base catalyzed (Dimroth) rearrangement of 1-CEA. The structure of N6-CEA was assigned on the basis of UV spectra and electron impact and isobutane chemical ionization mass spectra. When the carcinogen beta-propiolactone was reacted in vitro with calf thymus DNA, 1-CEA but not N6-CEA was detected on paper chromatograms following acid hydrolysis of the DNA. When BPL-reacted single-stranded DNA was incubated at pH 11.7 (37 degrees C, 18 h) prior to acid hydrolysis, it was found that 1-CEA was completely converted to N6-CEA in DNA by Dimroth rearrangement, whereas no conversion occurred at pH 7.5. The extent of Dimroth rearrangement at various pHs and temperatures was determined for 1-CEA, 1-methyladenine (1-MeA), 1-(2-carboxyethyl)-deoxyadenosine-5'-monophosphoric acid (1-CEdAdo5'P) and the phosphodiester 5'-O-(2-carboxyethyl)phosphono-1-(2-carboxyethyl)deoxyadenosine (1-CE-Ado-5'-P-CE).

Adenine↗
PubMed1979

Effects of structural changes on the tumor-promoting activity of phorbol myristate acetate on mouse skin.

4a alpha-Phorbol-9,9a-didecanoate, 4a alpha-phorbol-9-myristate-9a-acetate, and phorbol-9-myristate-9a-acetate-3-aldehyde were tested for skin tumor-promoting activity by using 7,12-dimethylbenz(a)anthracene as the initiating agent. There were 30 female ICR/Ha mice/group, and tests were continued for 434 to 461 days. 4a alpha-Phorbol-9,9a-didecanoate and 4a alpha-phorbol-9-myristate-9a-acetate were devoid of tumor-promoting activity. Phorbol-9-myristate-9a-acetate-3-aldehyde resulted in 10 mice with papillomas, 2 of which also bore squamous carcinomas of the skin. The positive control group, in which phorbol myristate acetate was used as promoting agent, resulted in 30 mice bearing multiple papillomas and 15 bearing squamous carcinomas of the skin. The effects of structural and stereochemical changes on tumor-promoting activity suggest that a primary interaction of the phorbol ester series is binding at specific sites on the plasma membrane.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1978

Antigenic differences between AKR lymphoma and thymus cells leading to detection of a tumor antigen associated with immunological enhancement.

In an experimental model conditioning for enhancement, an AKR lymphoma was made to grow in BALB/c mice, permitting the simultaneous comparison of tumor-bearing (progressor) and tumor-rejecting (regressor) animals. By immunofluorescence using as target AKR lymphoma and normal thymus cells, both acetone-fixed and unfixed, it was observed that the allogeneic progressor serum contained three antibodies, two of which could be asborbed by thymocytes while the other combined selectively with the acetone-fixed lymphoma target. This tumor-specific antibody could not be detected in regressor serum which, on the other hand, could be completely absorbed by thymocytes. The identification of this acetone-resistant tumor antigen led to the preparation of aceton-treated acellular lymphoma extracts: a precipitate was obtained which upon inoculation in BALB/c mice produced an antiserum that combined selectively with lymphoma targets. In vivo experiments showed that pretreatment with this antigen led to a significant increase in allogeneic tumor incidence, 76% as compared to 37% in the controls. It is concluded that in this allogeneic model, an acetone-resistant tumor-specific antigen and the corresponding antibody are involved in tumor enhancement.

Animals↗
PubMed1978

Structure and tumor-promoting activity of analogues of anthralin (1,8-dihydroxy-9-anthrone).

Seventeen analogues of the tumor-promoting agent anthralin were tested for the same biological property by repeated skin application on mouse skin using female ICR/Ha Swiss mice, after a single application of a subcarcinogenic dose of 7,12-dimethylbenz[a]anthracene. Seven of the compounds tested are new compounds. They are 1,8-diacetoxy-9-anthrone, 1,8-dimyristoyloxy-9-anthrone, 1,8-dihydroxy-10-acetyl-9-anthrone, 1,8-dihydroxy-10-myristoyl-9-anthrone, 1,8,10-trihydroxy-9-anthrone, 1,8-dihydroxy-9,10-dihydroanthracene, and myristoyljuglone. All compounds were used in pure form for the bioassays. Of the 17 test compounds four showed notable tumor-promoting activity. They are 1,8-dihydroxy-10-acetyl-9-anthrone, 1,8-dihydroxy-10-myristoyl-9-anthrone, 1-hydroxy-9-anthrone, and juglone. In order to determine whether there is any relationship between tumor-promoting activity and metal chelation in this series, the chelating abilities of anthralin and of its inactive analogue 1,8-dihydroxyanthraquinone were examined using the bivalent metal ions Cu(II), Zn(II), Mn(II), Mg(II), and Ca(II). No relationship between chelation and tumor-promoting ability was found.

Animals↗
PubMed1978

Tumor-promoting activity of 2,3-dihydrophorbol myristate acetate and phorbolol myristate acetate in mouse skin.

Phorbolol myristate acetate (PHMA) had been previously prepared from the potent mouse skin tumor promoter phorbol myristate acetate (PMA) by sodium borohydride reduction of the C-5 carbonyl group in PMA to a secondary alcohol. PHMA was shown to have an inflammatory effect in mouse skin equal to that of PMA. 2,3-Dihydrophorbol myristate acetate (DPMA), a new compound, was prepared from the 3-aldehyde of PMA by catalytic hydrogenation. DPMA exhibited no detectable inflammatory effect in mouse skin. Both DPMA and PHMA were tested on the dorsal skins of female ICR/Ha Swiss mice (30/group) for 433 and 380 days, respectively, in separate experiments. The tumor-promoting activity of both compounds was reduced significantly, compared with that of equimolar doses of PMA. For each treatment the number of mice with tumors per total number of tumors was: DPMA, 9/17; PMA, 29/553 at 10 microgram/mouse; PMA, 30/317; PHMA, 24/69 at 2.5 microgram/mouse. The results suggest that specific binding requirements influence the tumor-promoting and hyperplastic activity of PMA and its closely related derivatives in mouse skin.

Animals↗
PubMed1977

In vitro binding of beta-propiolactone to calf thymus DNA and mouse liver DNA to form 1-(2-carboxyethyl) adenine.

In vitro reaction of beta-propiolactone (BPL) with calf thymus DNA and mouse liver DNA followed by acid (HCL) hydrolyses of the BPL-reacted DNA's resulted in the isolation of a new compound, 1-(2-carboxyethyl)-adenine (1-CEA). The structure was assigned on the basis of ultraviolet spectra at acidic, alkaline and neutral pH and electron impact and chemical ionization mass spectra as well as chemical synthesis of 1-CEA from BPL and 2'-adenosine-5'-monophosphoric acid. The only other compound previously isolated from the in vitro and in vivo reactions of BPL and DNA was 7-(2-carboxyethyl)guanine (7-CEG) which we also identified as a product of our in vitro reaction. Under the conditions used the main product of alkylation was 1-CEA and the ratios of the concentrations of 1-CEA to 7-CEG was approx 3 : 1. The possible effect of the formation of 1-CEA on the structure of DNA and its role in chemical carcinogenesis is discussed.

Adenine↗
PubMed1977

Chagasic cardiopathy. Immunopathologic and morphologic studies in myocardial biopsies.

Immunopathologic and morphologic studies at the light and transmission electron microscope levels were carried out in myocardial biopsies of 4 chagasic individuals with circulating antibodies reacting with plasma membrane of striated muscle and endothelial cells (EVI antibody). Two cases did not present clinical evidences of heart involvement, and 2 cases showed chronic heart disease. In viv deposits of immunoglobulins were found at the plasma membrane of working myocardial cells and endothelial cells. The cytologic location of the in vivo bound gamma-globulin was coincident with the specificity of the EVI antibody. Ultrastructural studies showed intracellular alterations compatible with hypoxia of the fibers; these lesions, although they were more severe in the 2 cases with heart disease, were also present in the asymptomatic individuals. These results are congruent with a possible pathogenic effect of the EVI antibody. In 2 patients with Chagas' heart disease, foci of mononuclear infiltrates were examined by transmission electron microscopy. At that level, a close relationship between lymphoctes and muscle cells was observed, with imbrication of the plasma membranes and disappearance of the basal laminae. In the neighborhood of the lymphocytes, definite muscle cell abnormalities were found. These observations are also congruent with the recently suggested possibility that a lymphocyte-mediated immune response against heart tissue may participate in some of the pathogenetic mechanisms of chronic chagasic cardiopathy.

Adult↗
PubMed1976

In vitro acylation of the xi-amino group of L-lysine in calf thymus histones by the carcinogen, beta-propiolactone.

We had previously reported that the carcinogen, beta-propiolactone (BPL) reacted in vitro with histones in whole mouse skin chromatin and that among the histone classes BPL was preferentially bound to the lysine-rich histones H1 and H1 degrees. In order to determine if in vitro reaction of BPL with calf thymus histones resulted in binding of BPL to L-lysine, we synthesized the model compounds XI-N-(3-hydroxypropionyl)lysine (HPL) and xi-N-(I-carboxyethyl)lysine (CEL) from BPL and L-lysine. The alpha-amino group of L-lysine was protected from reaction with BPL by the formation of a copper chelate. Structures were assigned on the basis of infrared spectra, pKa values and chemical analyses. BPL was reacted in vitro with calf thymus histones and the BPL-reacted calf thymus histones and control calf thymus histones were digested with trypsin followed by pronase. The respective digests were each chromatograhed on a column of AA-15 cation-exchange resin. The elution profiles of the two digests were very similar except for the appearance of a new ninhydrin-positive peak (NNPP) in the eluate of the trypsin-pronase digest of BPL-reacted calf thymus histones. When compounds HPL and CEL were added to the trypsin-pronase digest of control calf thymus histones and the mixture chromatographed on AA-15, both compounds were resolved from the other peptide (or amino acid) peaks. HPL was eluted in the same fractions as NNPP, HPL and NNPP exhibited identical RF values on silica gel TLC with acidic, alkaline and neutral solvents. CEL was not identified as a product of the reaction between BPL and calf thymus histones.

Animals↗
PubMed1976

Lorazepam and diazepam in anxious outpatients. A controlled study.

The response of 134 anxious neurotic outpatients to lorazepam, diazepam, and placebo was assessed in a 4-week double-blind trial. Both active drugs produced significantly more symptom reduction than placebo. Lorazepam, however, proved effective primarily in those patients who did not complain of sedation, and produced greatest improvement in initially sicker patients. Sedation was significantly more disturbing to lorazepam-treated patients than to diazepam-treated patients. Present findings suggested that 3 mg/day of lorazepam may be too high a dosage for mildly anxious patients, while 15 mg/day of diazepam seems an appropriate dosage for mildly anxious patients but may be too low a dosage for highly anxious patients.

Adult↗
PubMed1976

Inhibition of two-stage carcinogenesis in mouse skin with bis(2-chloroethyl)sulfide.

ICR/Ha Swiss mice, 30 females/group, were given a single application of 20 mug 7,12-dimethylbenz(a)anthracene, followed 2 weeks later by three times weekly applications of phorbol myristate acetate (PMA), 2.5 mug/application. In the accompanying inhibition experiments, sulfur mustard [SM; bis(2-chloroethyl)sulfide] was applied at a dose of 20 mug/application during the promotion phase, either on the same day as PMA, i.e., three times weekly, or on alternate days, i.e., twice weekly. The experiments were continued for 385 days. The control group, i.e., without SM, resulted in 27 of 30 mice with a total of 281 papillomas. Sixteen of these mice also bore squamous cell carcinomas. In the two groups also receiving SM, two or three times weekly, 2 of 30 and 1 of 30 mice, respectively, bore papillomas. Carcinomas were not observed in these groups. The inflammatory response of mouse skin to the combined treatments of SM and PMA was no greater than with PMA alone.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Ultrastructural and immunohistochemical study of the human kidney in Argentine haemorrhagic fever.

In six lethal cases of Argentine Haemorrhagic Fever (AHF) a disease caused by Junin virus, kidney samples were studied by means of immunofluorescent and electron microscopic techniques.--The ultrastructural studies showed that the distal and collecting tubes presented a large number of virus like intracytoplasmic particles. Those particles were present in the lumen of the endoplasmic reticulum cisternae and showed two distinct morphological aspects. Some of them were of high electron density and contained a few granules. The others were larger in size, electron lucid, and contained a variable number of ribosome like granules. Both types of particles originated from the endoplasmic reticulum wall by a process of budding. The presence of these particles was coincident with a severe cell damage which lead to necrosis and desquamation; and with large quantities of Junin virus antigen as demonstrated by immunofluorescence.--On the basis of these observations it is assumed that in AHF the cell damage is due to direct viral replication within the affected cells.

Antigens, Viral↗
PubMed1975

Ultrastructural and immunohistochemical studies in five cases of Argentine hemorrhagic fever.

Ultrastructural and immunohistochemical studies on tissues from five patients with Argentine hemorrhagic fever revealed previously undetected lesions caused by the viral infection. Two types of particle were seen in the cells of all organs examined. The particles had some characteristics similar to those described for arenaviruses. However, the virus-like particles were intracellular, had a single membrane, and apparently originated by a process of budding into the endoplasmic reticulum cisternae. Intranuclear bodies and three types of cytopolasmic change were observed in conjunction with the virus-like particles; Antigenic determinants of Junin virus were demonstrated in cells of all organs examined. Immunohistochemical experiments also indicated alterations in the cellular mechanisms of protein synthesis. Until now the pathogenesis of human diseases produced by arenaviruses has not been established. The results of this study suggest that in Argentine hemorrhagic fever the virus is responsible for a direct pathogenic action.

Adult↗
PubMed1975

The identification of phorbolol myristate acetate as a new metabolite of phorbol myristate acetate in mouse skin.

Aspects of the metabolism of phorbol myristate acetate (PMA) in mouse skin were investigated. Phorbolol myristate acetate (PHMA), a potential metabolite of PMA in mouse skin, was prepared from PMA by NaBH4 reduction of the C-5 carbonyl group of PMA to a secondary alcohol. The structure of PHMA was assigned on the basis of spectral and chemical evidence. PHMA had an inflammatory effect in mouse skin equal to or slightly less than PMA, on the basis of the dermal infiltration of lymphocytes and neutrophils and interfollicular epidermal hyperplasia. Application of PHMA and PMA to mouse skin resulted in equal increases in numbers of interfollicular epidermal basal layer mitotic cells after 28 hr. PHMA was found to be nearly as effective as PMA in increasing the incorporation of [3H]thymidine into interfollicular epidermal basal layer cells after 28 hr. When tritiated PMA was applied to mouse skin, PHMA was identified as a metabolite. PHMA was present in about 1.7% of the amount of PMA. When tritiated PHMA was applied to mouse skin, PMA was not detected as a metabolite in the mouse skin extracts.

Animals↗