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Biomedical subjects

A Pollack

Publications and source records attributed to A Pollack.

At least 217 records · Page 12Linked to original sources

Effects of the gonadotropin-releasing hormone agonist [D-leu6, desgly-NH2(10), proethylamide9]-GnRH (leuprolide) on R3327-G rat prostatic tumor growth.

The synthetic gonadotropin releasing hormone agonist [D-leu6, desgly-NH2(10), proethylamide9]-GnRH (leuprolide) was tested for its ability to inhibit androgen-sensitive R3327-G rat prostatic tumor growth in Copenhagen X Fischer F1 male rats. The chronic administration of leuprolide at 50 micrograms per kg. body weight or 1000 micrograms per kg. body weight significantly reduced serum testosterone levels and testis weights. Only chronic leuprolide administration at high concentration (1000 micrograms per kg.) compared with orchiectomy in reducing the rate of tumor growth, prolonging survival, and affecting changes in DNA content per cell as quantitated by flow cytometry. The DNA content changes and cell kinetic responses of R3327-G tumors to these treatments were related to the extent to which serum testosterone levels were reduced. The data suggest that for some prostatic cancers gonadotropin releasing hormone agonist administration must reduce serum testosterone levels to those achieved by orchiectomy for maximal growth rate inhibition.

Animals↗

Congenital glaucoma and incomplete congenital glaucoma in two siblings.

The case histories and eye findings of 2 siblings of a non-sanguinous marriage are reported. The first child, a girl, had the typical findings of a unilateral congenital glaucoma. Her brother had an enlarged unilateral cornea (13 mm) without Descemet breaks, and normal intraocular pressure on repeated follow-up examination over 4 years. Gonioscopy showed numerous iris processes covering the iridocorneal angle. Fundus examination revealed a cup-disc ratio of 0.4 in the affected eye and 0.1 in the normal eye. Patients whose clinical picture resembles that of our second patient should be classified as having incomplete or abortive congenital glaucoma; such patients may develop raised intraocular pressure at a later stage. The term megalocornea should be reserved for eyes with enlarged cornea, normal intraocular pressure, normal iridocorneal angles, no cup-disc asymmetry and no family history of congenital glaucoma.

Cornea↗

Ocular findings in the acquired immunodeficiency syndrome.

A patient with acquired immunodeficiency syndrome is described. Both retinae were severely affected. Vision was reduced to light perception with projection incerta in the right eye and finger counting at 1.5 m in the left eye. Eye involvement is common in this syndrome, appearing at an early stage of the disease. The fundal appearance could thus be of help in diagnosis.

Acquired Immunodeficiency Syndrome↗

Prophylactic laser photocoagulation in hereditary snowflake vitreoretinal degeneration. A family report.

Examination of 37 members of a family revealed that 17 had snowflake vitreoretinal degeneration. All those affected showed some evidence of vitreous degeneration and 13 had retinal changes with differing degrees of severity. Vitreal changes may thus present as an early stage when hardly any retinal pathology is apparent. Peripheral retinal neovascularization was seen in four patients. Rhegmatogenous retinal detachment developed in two eyes and retinal breaks in six additional eyes. Because of the poor surgical prognosis in such cases, prophylactic treatment with argon laser photocoagulation is recommended for any type of retinal break.

Adolescent↗

In vivo selection of androgen-insensitive cells in R3327-G rat prostate tumors: diethylstilbestrol diphosphate treatment versus orchiectomy.

Tumors grown in diethylstilbestrol diphosphate (DES)-treated rats grew significantly more slowly than tumors grown in orchiectomized animals, and tumors grown in orchiectomized animals grew significantly more slowly than tumors grown in controls (intact male rats). When these tumors (phase I) were dispersed and reimplanted into DES-treated, orchiectomized, or control rats in all possible combinations (phase II), a partial selection of androgen-insensitive cells was observed in tumors grown in DES-treated animals. Tumors grown in DES-treated phase I animals responded significantly less to DES treatment or orchiectomy in phase II. In contrast, tumors from phase I orchiectomized animals showed the same responses to orchiectomy in phase II. Since the administration of exogenous testosterone propionate prevented the growth rate inhibitory effects of both DES treatment and orchiectomy, the added effect of DES seemed to be antiandrogenic.

Adenocarcinoma↗

Flow cytometric analysis of RNA content in different cell populations using pyronin Y and methyl green.

Pyronin Y (PY) was used, in flow cytometric (FCM) systems, to estimate the RNA content per cell in formalin fixed EL4 leukosis tumor cells, enzyme dispersed R3327-G rat prostatic adenocarcinoma cells, mouse spleen cells stimulated with concanavalin A, and human peripheral blood lymphocytes stimulated with phytohemagglutinin. Preincubation of the cells with methyl green (MG) blocked PY binding to DNA such that the intracellular fluorescence from MG-PY was due primarily to its binding to RNA. Treatment of the cells with ribonuclease resulted in a 3- to 5-fold reduction in the fluorescence intensity of intracellular MG-PY. Mitogen stimulation of either mouse or human lymphocytes resulted in an increase in DNA (propidium iodide fluorescence) and RNA (MG-PY fluorescence) content per cell over resting levels. Further, the changes in stimulated human lymphocyte DNA and RNA contents following 24, 48, and 72 hr of cell culture were monitored. The results showed that RNA levels were significantly increased prior to that of DNA. Also, the effects of different cell cycle phase specific blocking agents on lymphocyte cell cycle traverse were investigated. We found that: a) actinomycin D inhibited the increases in cellular RNA and DNA; b) hydroxyurea inhibited the increases in cellular RNA were only slightly reduced; c) tritiated thymidine caused an accumulation of cells having high DNA and RNA contents; and d) Colcemid promoted an accumulation of cells having high DNA contents while causing a reduction of cells having high RNA contents. These results were nearly identical to reports by other investigators using the metachromatic dye acridine orange to quantitate RNA per cell. Thus, the MG-PY technique described is indicated to provide a stable and accurate measure of RNA content per cell.

Animals↗

Infection with Mycobacterium avium-intracellulare and the protective effects of Bacille Calmette-Guérin.

The protective efficacies of bacille Calmette-Guérin (BCG) and Mycobacterium avium-intracellulare (MAI) were examined in guinea pigs that were infected by the respiratory route with one of three strains of Mycobacterium tuberculosis: two strains obtained as recent sputum isolates from an ongoing BCG trial in south India and laboratory strain H37Rv. Groups of animals were given all combinations of two treatments with BCG, MAI, or placebo and than challenged. The numbers of tubercle bacilli recovered from the primary lung lesions, primary lesion-free lung lobes, and spleens were used to estimate the relative protective effects of the various treatments. In general, BCG and MAI protected equally well against the low-virulence strain of M. tuberculosis. For the two more virulent strains the results were less clear; however, a substantial protective effect of MAI compared with BCG was noted. Infection with MAI did not significantly alter the capacity of BCG to protect against tuberculous infection.

Animals↗

Flow cytometric analysis of R3327 rat prostate adenocarcinoma grown in vivo and in vitro.

The Dunning R3327 transplantable prostate adenocarcinoma in the Copenhagen rat is an acceptable model for the human disease. The G-subline (a rapidly growing carcinoma) and the H-subline (a slow-growing, well-differentiated adenocarcinoma) represent the extremes of differentiation and growth rate of this tumor. Both sublines were found to have one population that was diploid and a second aneuploid population that was hyperdiploid in DNA content. The percentage of hyperdiploid cells was significantly higher in R3327-G tumors than in R3327-H tumors. The tumor cell population ratios were stable in vivo, but the in vitro culture conditions supported only cells with diploid DNA content following four to five subcultures. These predominantly diploid cultured cells, when injected into intact male rats, resulted in tumors that had both diploid and aneuploid cells.

Adenocarcinoma↗

Hormone sensitivity of the R3327-G rat prostate adenocarcinoma: growth rate, DNA content, and hormone receptors.

The growth of the R3327-G rat prostatic adenocarcinoma was significantly reduced when implanted in orchiectomized male rats (ORCH tumors). Tumors grown in intact animals (control tumors) had a doubling time of 7.4 days as compared to 9.2 days in ORCH tumors. A computer-based analysis of flow cytometric DNA histograms also detected significant differences between control and ORCH tumors. ORCH tumors were found to have 25% fewer cells with hyperdiploid DNA than control tumors (p less than 0.01). This androgen sensitivity in growth rate and the proportion of hyperdiploid cells were further reflected in the binding of [3H]methyltrienolone ([3H]-R1881) to cytoplasmic (cytosol) and nuclear tumor extracts. ORCH tumor cytosols had a [3H]R1881 binding capacity which was 70% lower than controls (6071 fmol/g tumor tissue). Nuclear [3H]R1881 binding in ORCH tumors was undetectable in seven of eight samples while in control tumors, binding was detectable in five of six preparations. Sucrose density gradient analysis showed that cytosolic [3H]R1881 receptors sedimented at 8.1 S in low salt and 4.6 to 3.3S in high salt. Nuclear [3H]R1881 receptors in high salt sedimented at 4.1 to 3.3S. Competition experiments using [3H]R1881 showed that [3H]-R1881 receptors were primarily androgenic, although some displacement by estradiol did occur. In contrast, [3H]estradiol binding was found to be highly specific. The binding capacity of [3H]estradiol in ORCH tumor cytosols was 30% higher than controls (962 fmol/g tumor issue), while binding to ORCH and control nuclear extracts was similar. These data suggest that the inhibition of androgen-sensitive R3327-G tumor cells was related to the concentration of androgen receptors and that this in turn was expressed as a reduction in the proportion of hyperdiploid cells.

Adenocarcinoma↗

Flow cytometric analysis of the response of the R3327-G rat prostatic adenocarcinoma to endocrine manipulation.

The technique of flow cytometric DNA histogram analysis (FCM) shows there to be two distinct cell populations (diploid vs aneuploid) in the poorly differentiated R3327-G rat prostatic adenocarcinoma. The following study compares tumor weight measurements with several FCM computer-based methods designed to determine rapidly the proliferative status of tumors. Hypophysectomy, bilateral adrenalectomy, orchiectomy, sham operations, or diethylstilbestrol treatments were initiated when the tumors were palpable (day 21) and continued until the tumors were excised (day 52). Hypophysectomy, orchiectomy, adrenalectomy, and diethylstilbestrol treatments all resulted in significant inhibition by tumor weight. Quantitation of the percentage of mid-S phase aneuploid cells by summation gave the best correlation with tumor weight. Tumors grown in hypophysectomized, orchiectomized, adrenalectomized, or diethylstilbestrol-treated animals showed a significant reduction in the proportion of mid-S phase cells as compared with controls. The calculation of the percentage of all aneuploid cells was significantly reduced in hypophysectomy, orchiectomy, and diethylstilbestrol-treated animals. However, tumors grown in adrenalectomized animals were not significantly different from controls by this method. Adrenalectomy was found to be the least effective form of therapy, and this was reflected in all of the parameters measured. These data show that FCM analysis may be useful in the quantitation of prostatic carcinoma response to therapy.

Adenocarcinoma↗

Flow cytometric monitoring of R 3327 rat prostate carcinoma.

The R 3327 G tumor responds to estrogen in early stages, but relapses when estrogen therapy is continued beyond 50 days postimplantation. Measurement of DNA content per cell by flow cytometric analysis revealed two populations of cells in the tumors with ploidies of 2 c and 3.2 c. The proportion of aneuploid cells (3.2 c), determined from the flow cytometric DNA distributions, correlated well with tumor weight and age in control and estrogen treated animals. The simple parameter of per cent aneuploid cells thus adequately reflected the responsive and unresponsive states of tumors under hormonal therapy.

Aneuploidy↗

The kinetics of the formation of a G2 block from tritiated thymidine in phytohemagglutinin-stimulated human lymphocytes.

Flow cytometry (FCM) was used to monitor the radiation effects promoted by incorporated tritiated thymidine (3H-TdR) on phytohemagglutinin (PHA)-stimulated human peripheral blood lymphocytes stained with propidium iodide (PI). Lymphocyte microcultures were continuously labeled or pulse-labeled for various periods of time with different 3H-TdR concentrations. Two types of DNA histogram analyses were performed on unperturbed and 3H]TdR perturbed lymphocytes. The data analyses consisted of statistical analyses between averaged groups of histograms (nonparametric analysis) and cell cycle analyses (parametric analysis) to determine the percentages of cells in G0 + G1, S and G2 + M. The results showed that (a) 3H-TdR when added to proliferating lymphocytes under certain conditions (both short-term continuous and pulse-labeling) caused a highly significant increase in the proportion of tetraploid (4C) cells by FCM, (b) the increase in the proportion of 4C cells represented a block in G2 and (c) the relative increase in the percentage of 4C cells was proportional to 3H-TdR incorporation which was proportional to labeling time and concentration. Therefore, it was concluded that short labeling times be used to minimize adverse radiation effects when 3H-TdR is used to assay substances affecting lymphocyte proliferation or in the estimation of cell cycle time.

Adolescent↗

Differences in flow cytometry and 3H-thymidine analyses of perturbed human lymphocytes.

A calf thymocyte crude aqueous extract was tested for DNA synthesis inhibitory activity using phytohemagglutinin-stimulated human peripheral blood lymphocytes. Inhibition of DNA synthesis was assayed using tritiated thymidine and flow cytometry. Although the calf thymocyte crude extract inhibited tritiated thymidine incorporation by over 50%, only very slight changes in the flow cytometric analysis were observed. When dibutyryl-cyclic adenosine monophosphate was used as an inhibitor, a correlation in terms of the inhibition of tritiated thymidine to the inhibition by flow cytometry was observed.

Animals↗

(-)-Hydroxycitrate and conditioned aversions.

The capacity of various salts of (-)-hydroxycitrate to produce conditioned rejection of a 0.25% saccharin solution was evaluated. The ethylenediamine salt of (-)-hydroxycitrate produced strong conditioned rejection of saccharin under both deprivation and nondeprivation conditions, but this effect was less than produced by equimolar doses of lithium chloride. The sodium salt of hydroxycitrate produced no conditioned rejection of saccharin in water deprived rats but did so in nondeprived animals. In these experiments, food intake was reduced by (-)-hydroxycitrate only during the first hour following administration of the drug. The magnitude of appetite rejection did not correspond to the degree of conditioned rejection, lending support to the conclusion that the food intake reduction was not merely a consequence of aversive effects of the drug.

Animals↗

Deoxyribonucleic acid replication in single cells and chromosomes by immunologic techniques.

Antibodies to 5-bromodeoxyuridine (BrdU) or iododeoxyuridine may be used to identify cells or regions of chromosomes in which de novo deoxyribonucleic acid synthesis has occurred. The antibodies to BrdU were produced in rabbits by injection of the antigen, a conjugate between bovine serum albumin and bromouridine (BrU), or iodouridine. Specific antibodies were produced by affinity chromatography on AH-Sepharose 4B to which had been coupled BrU. Anti-BrU cross-reacts with iodeodeoxyuridine. Indirect antibody techniques have been used to monitor deoxyribonucleic acid synthesis in nuclei; anti-BrdU treatment was followed by goat anti-rabbit immunoglobulin G labeled with either fluorescein or horseradish peroxidase. By use of these techniques, labeling indices were determined in cell cultures which had been pulsed with 3H-BrdU. The immunologic technique compared favorably with the autoradiographic methods performed concurrently on the same cultures. Metaphase chromosomes from synchronous CHO cell which had been pulse labled with BrdU at different time intervals during S phase were subjected to these immunologic procedures. Chromosome banding was observed with both the fluoresence and peroxidase methods. Chromosomes from cells not containing BrdU did not exhibit banding.

Antibodies↗