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J Sawyer

Publications and source records attributed to J Sawyer.

At least 55 records · Page 3Linked to original sources
PubMed1989

Cytogenetic analysis of two C-1300 murine neuroblastoma cell lines expressing discordant malignant behavior.

Cytogenetic analysis of two murine neuroblastoma cell lines that show different malignant expression revealed consistent differences in the chromosomal composition between the two lines. The MNB-T1 (high-malignancy) cell line showed increased modal chromosome number, presence of homogeneously staining regions (HSRs), double minutes (dmin) and evidence of secondary chromosomal events when compared with the MNB-T2 (low-malignancy) cell line, which did not express these cytogenetic characteristics. Several of the cytogenetic events that have occurred in these murine cell lines, such as HSRs, dmin, and chromosomal deletions, have also been reported in human neuroblastoma cell lines. When comparisons are made for the involvement of chromosomal regions known to be involved in human neuroblastoma, similar tumor specific regions seem to be involved in the homologous mouse chromosomes.

Animals↗
PubMed1989

Intensity of Schistosoma mansoni infection in a human population is inversely correlated with antibody response to SmW68, a protective parasite antigen.

Vaccination with SmW68, a Schistosoma mansoni surface antigen, significantly protects mice against challenge infection. To investigate the vaccine potential of SmW68 in clinical schistosomiasis, human antibody response to SmW68 was studied as a function of intensity of infection in a chronically infected Egyptian population. In 85 serum samples obtained randomly from families in El Gazairy (population 1,310), antibody to SmW68 (determined by ELISA) was found to increase significantly with age, reaching a plateau at 15-19 y, 1-5 y after peak prevalence and intensity of infection. Among infected individuals (n = 54), antibody response showed a significant inverse correlation (r = -.28, P less than .04) with intensity of infection. In isotype analysis, a higher IgM but not IgG response was significantly associated with low parasite burden. These studies demonstrate that significant antibody response to SmW68 could occur in chronically infected humans. Whether parasite burdens suppress circulating levels of antibody to SmW68 or whether enhanced antibody response to SmW68 represents acquired protective humoral immunity remains to be determined.

Adolescent↗
PubMed1985

Analysis of trifluorothymidine-resistant (TFTr) mutants of L5178Y/TK+/- mouse lymphoma cells.

Three classes of TFTr variants of L5178Y/TK+/- -3.7.2C mouse lymphoma cells can be identified--large colony (lambda), small colony (sigma), and tiny colony (tau). The sigma and lambda mutants are detectable in the routine mutagenesis assay using soft agar cloning. The tau mutants are extremely slow growing and are quantitated only in suspension cloning in microwells. Variants of all three classes have been analyzed in the process of evaluating the usefulness of the thymidine kinase locus in L5178Y/TK+/- mouse lymphoma cells for detecting induced mutational damage. 150 of 152 variants from mutagen treated cultures and 163 of 168 spontaneous mutants were TFTr when rechallenged approximately 1 week after isolation (3 weeks after induction). All of the 41 mutants assayed for enzyme activity were TK-deficient. The sigma and tau phenotypes were found to correlate with slow cellular growth rates (doubling time greater than 12 h), rather than from effects of the TFT selection or mutagen toxicity. Cytogenetic analysis of sigma mutants approximately 3 weeks after induction shows an association between the sigma phenotype and readily observable (at the 230-300 band level) chromosomal abnormalities (primarily translocations involving that chromosome 11 carrying the functional TK gene) in 30 of 51 induced mutants studied. Using an early clonal analysis of mutants (approximately 2 weeks after induction) 28 of 30 sigma mutants showed chromosome 11 rearrangements. All lambda mutants studied (17 of 17 evaluated 3 weeks after induction and 8 of 8 evaluated 2 weeks after induction) showed normal karyotypes (at the 230-300 band resolution level), including the chromosome 11s. These observations support the hypothesis that sigma (and likely tau) mutants represent chromosomal mutations and lambda mutants represent less extensive mutations affecting the TK locus. The inclusion of sigma mutants in the total induced mutant frequency, as well as distinguishing them as a separate subpopulation of TK-deficient mutants, is, therefore, essential in obtaining maximum utility of the information provided by the L5178Y/TK+/- mouse lymphoma assay.

Animals↗
PubMed1985

Chromosome 11 aberrations in small colony L5178Y TK-/- mutants early in their clonal history.

We have developed a cytogenetic technique that allows observation of chromosome rearrangements associated with TK-/- mutagenesis of the L5178Y/TK+/-3.7.2C cell line early in mutant clonal history. For a series of mutagenic treatments we show that the major proportion (93%) of small-colony (sigma) mutants studied have chromosome 11 rearrangements (the chromosome containing the thymidine kinase gene) while large-colony (lambda) mutants do not have detectable chromosome rearrangements. In addition, we find among the chromosome abnormalities in sigma mutants a significant proportion (34%) with dicentric chromosomes involving chromosome 11. These potentially unstable chromosome rearrangements may help to explain the karyotypic instability and heterogeneity among chromosome 11 aberrations previously noted in sigma mutants when they are analyzed later in their clonal history.

Animals↗
PubMed1985

Cytogenetic characterization of the L5178Y TK+/-3.7.2C mouse lymphoma cell line.

The cytogenetic characterization of the L5178Y TK+/-3.7.2C mouse lymphoma cell line was carried out, utilizing G-banded metaphase chromosomes, to provide a karyotypic basis for the precise delineation of induced rearrangements in TK-/- mutants. Band-pattern measurements were used to construct ideograms which represent the position, number, size and staining intensity of the chromosome bands. The TK+/-3.7.2C cell line has been shown to provide quantitation of forward mutations induced at the autosomal thymidine kinase (TK) locus in this cell line. Chromosome analysis of the TK+/-3.7.2C cell line and derived TK-/- mutants has become important in demonstrating that the TK+/-----TK-/- assay may detect and distinguish between chromosomal events and smaller, perhaps point-mutation, events in mutant colonies.

Animals↗
PubMed1985

Gene mapping and leader polypeptide sequence of human glucocerebrosidase: implications for Gaucher disease.

Analysis of immunologic cross-reacting material in Chinese hamster-human somatic cell hybrids allowed assignment of the structural gene for glucocerebrosidase (glucosylceramidase; beta-D-glucosyl-N-acylsphingosine glucohydrolase, EC 3.2.1.45) to chromosome 1 bands q21-q32. In situ hybridization of a radiolabeled human glucocerebrosidase cDNA to high resolution human chromosomes demonstrated that a single locus encoding glucocerebrosidase is on 1q21, adjacent to a region of chromosome 1 (1qh) abundant in structural heteromorphisms. We also have identified a hydrophobic leader polypeptide encoded by this locus, permitting a more complete description of the biosynthesis of the enzyme. These results suggest that the type-specific protein polymorphisms in Gaucher disease result from mutations at this single locus, whose segregation might be followed by linkage to visible chromosomal heteromorphisms.

Animals↗
PubMed1984

The dexamethasone suppression test in schizophrenia.

In a study of 20 inpatients who met DSM-III criteria for schizophrenia, there was a high incidence of depressed mood (N = 14), DSM-III melancholia (N = 6) and dexamethasone nonsuppression (N = 7). This incidence of positive DSTs (serum cortisol greater than 5 micrograms/dl at 3:30 or 10:00) was significantly higher than the expected rate based on a literature review (35% vs. 4%, p less than .001). A positive DST did not result in all cases in antidepressant pharmacotherapy, nor did a negative result preclude such treatment. Hence, clinicians in the study did not "treat the DST" in the absence of clinical evidence of depression. This study is consistent with others reporting a significant proportion of depressed schizophrenics. However, some studies have claimed no differences in response to dexamethasone between nondepressed and schizophrenic patients. These findings do not support a biological basis for the RDC differentiation of primary and secondary depression and challenge the DSM-III concept of schizophrenia as excluding the diagnosis of major depression. Viewed from a different perspective, the data may support recent reports casting doubt on the specificity of the DST.

Adult↗
PubMed1982

Studies on the long term effects of SK&F 29661 upon adrenal catecholamines.

SK&F 29661 (1,2,3,4-tetrahydro-7-isoquinoline-sulfonamide) is a potent and selective in vitro and in vivo inhibitor of adrenal phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28). Its Ki value for in vitro inhibition of rat adrenal PNMT was 133 nM. In vivo, the adrenal conversion of 3H-norepinephrine to 3H-epinephrine was maximally inhibited by a single oral dose of 100 mg/kg. In long term chronic studies in rats, adrenal epinephrine was reduced by SK&F 29661 in a dose dependent fashion to greater than 90%, without substantial increases in norepinephrine. Urinary excretion of epinephrine was significantly reduced by the drug both basally and following 2-deoxy-D-glucose stimulation. No drug related changes were found in plasma corticosterone values and only small effects were observed on adrenal tyrosine hydroxylase and PNMT enzyme levels. The cardiac norepinephrine pool and its turnover time were both significantly reduced; its turnover rate, however, was only slightly increased. Our studies indicate that SK&F 29661 is a highly effective, non-toxic and novel pharmacological tool which is useful in depleting adrenal epinephrine stores via inhibition of its biosynthesis.

Adrenal Glands↗
PubMed1982

Consumption of foods and nutrients by weanlings in rural Bangladesh.

Longitudinal studies of the consumption of foods and nutrients by 70 children between 5 and 30 months of age have been completed, during 632 individual days of observation in rural village homes in Bangladesh. Foods and prepared menu items for each child were weighed before serving; leftover food was subtracted from portions served to determine the amounts consumed. Breast milk intakes were estimated by test-weighing of children before and after all feedings during 12-h daytime periods and were corrected to 24-h consumption. All children between 5 and 12 months of age and 85% of children between 24 and 30 months were breast-fed; the average amount of breast milk received by these age groups declined from 632 to 368 g/day. Concurrently, the rate of consumption of cereals increased from 54 to 100% of children, and the amount received increased from 35 to 94 g/day. The children received an average intake of energy between 63 to 71 kcal/kg body weight/day and an average intake of protein between 1.2 to 1.5 g protein/kg body weight/day in the various age and sex categories. The absolute consumption of energy and protein increased with age, but the amount of energy per kg of body weight and the percentage of energy requirement for the amount of energy per kg of body weight and the percentage of energy requirement for length-age remained constant or declined in older girls. Vitamin A consumption, mostly from breast milk, averaged between 152 and 249 micrograms retinol equivalents per day, with younger children receiving more than older ones and boys receiving more than girls. Breast milk was the major source of all nutrients for younger children. Cereals provided more protein and iron than mothers' milk in older boys, but breast milk remained an important source of nutrients for all children.

Age Factors↗
PubMed1981

Cytogenetic analysis of the L5178Y/TK+/- leads to TK-/- mouse lymphoma mutagenesis assay system.

The L5178Y/TK+/- leads to TK-/- mouse lymphoma mutagen assay, which allows selection of forward mutations at the autosomal thymidine kinase (TK) locus, uses a TK+/- heterozygous cell line, TK+/- 3.7.2C. Quantitation of colonies of mutant TK-/- cells in the assay forms the basis for calculations of mutagenic potential of test compounds. We have evaluated the banded karyotypes of the parent TK+/- heterozygous cell line, as well as homozygous TK-/- mutants, in order to relate the genetic and morphological properties of mutant colonies. The parent cell line displays karyotype homogeneity, all cells containing normal mouse chromosomes, readily identifiable chromosome rearrangements, and cell line specific marker chromosomes. Mutant TK-/- colonies of the TK+/- 3.7.2C cell line form a bimodal frequency distribution of colony sizes for most mutagenic or carcinogenic test substances. Large-colony (lambda) TK-/- mutants with normal growth kinetics appear karyotypically identical within and among clones and with the TK+/- parental cell line. In contrast, most slow-growing small-colony (sigma) TK-/- mutants have readily recognizable chromosome rearrangements involving chromosome 11, which contains the thymidine kinase gene locus. It is possible that the heritable differences in growth kinetics and resultant colony morphology in lambda and sigma mutants are related to the type of chromosomal damage sustained. Large-colony mutants receive minimal damage, possibly in the form of point mutations at the TK locus, while small-colony mutants receive damage to other genetic functions coordinately with loss of TK activity, implying gross insult to chromosomal material. It seems likely that lambda and sigma mutants result from 2 different mutational mechanisms that may be distinguished on the basis of mutant colony morphology.

Animals↗
PubMed1980

Comparison of the effects of SK & F 29661 and 64139 upon adrenal and cardiac catecholamines.

After 7 day dosing with SK & F 64139, an inhibitor of adrenal and CNS PNMT, a stoichiometric relationship is observed between epinephrine decrease and norepinephrine increase in adrenal tissue. However, this relationship is not found with the adrenal PNMT inhibitor, SK & F 29661. SK & F 64139 was found to possess significant adrenal MAO inhibitory activity, but SK & F 29661 does not. Three factors are presented which argue against MAO inhibition as the cause of the catecholamine profile difference. We then performed various studies with SK & F 29661 and 64139 to examine whether enzymes in the norepinephrine biosynthetic pathway are differentially affected by these drugs and found that they were not. However. when rats were dosed with either SK & F 29661 or 64139 over 24 h and the adrenal catecholamine stores were then radioactively labeled with a tracer dose of 3H-norepinephrine, the rate of 3H-norepinephrine disappearance was reduced in the SK & F 64139-treated animals as compared with those given SK & F 29661. A similar result was observed in the heart. These results suggest that SK & F 64139 may reduce norepinephrine turnover in the adrenal gland and heart via an effect not related to peripheral PNMT inhibition. These findings also demonstrate quite clearly that in intact animals all PNMT inhibitors do not produce identical endogenous catecholamine profiles.

Adrenal Glands↗
PubMed1980

Studies on lung N-methyltransferases, a pharmacological approach.

Phenylethanolamine N-methyltransferase (PNMT) was identified as the primary, high affinity N-methylating enzyme for phenylethanolamine (PEA) in rat, dog and Rhesus monkey lung. Human and rabbit lung, however, do not contain this enzyme but possess a more non-specific or general N-methyltransferase with a relatively low affinity for PEA and for which beta-phenethylamine (beta-PE) is also a substrate. The former but not the latter enzyme is markedly inhibited by micromolar concentrations of the PNMT antagonist, SK & F 64139. This evidence indicates that certain species differences exist for the enzyme system(s) available for the N-methylation of phenethylamine-type compounds in pulmonary tissue.

Animals↗
PubMed1979

Studies on SK&F 29661, an organ-specific inhibitor of phenylethanolamine N-methyltransferase.

SK&F 29661 is an effective, reversible inhibitor of both central nervous system and adrenal phenylethanolamine N-methyl-transferase in vitro; its Ki values in our standard assay systems were 6 X 10(-7) M (central nervous system) and 3 X 10(-7) M (adrenal), respectively. In vivo, the drug inhibited the conversion of [3H]norepinephrine to [3H]epinephrine in the rat adrenal gland and upon chronic administration decreased the endogenous adrenal epinephrine/norepinephrine ratio in both the rat and squirrel monkey. SK&F 29661 did not, however, reduce rat brain stem PNMT activity after systemic administration; subsequent radioautographic studies indicated that the compound did not enter the central nervous system, presumably because of its high polarity. This drug may be useful in defining the physiological importance of peripheral phenylethanolamine N-methyltransferase inhibition.

Adrenal Glands↗