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S Strom

Publications and source records attributed to S Strom.

35 records · Page 2Linked to original sources
PubMed1990

Interleukin-1 beta, human leukocyte antigen HLA-DR alpha, and transforming growth factor-beta expression in endometrium, placenta, and placental membranes.

Maternal immune recognition of the fetal semiallograft appears to be necessary and beneficial for fetal survival and growth. Interleukin-1 beta and human leukocyte antigen HLA-DR are important for foreign antigen recognition by the immune system, whereas transforming growth factor-beta inhibits many of the immunostimulatory properties of interleukin-1 beta. In this study we found that first-trimester decidua and term placental membranes expressed significantly higher levels of interleukin-1 beta, interleukin-1 beta messenger ribonucleic acid, and human leukocyte antigen HLA-DR alpha messenger ribonucleic acid expression. All tissues found at the maternal-fetal interface, including first-trimester decidua, placenta, and placental membranes, contained transforming growth factor-beta and expressed transforming growth factor-beta 1 messenger ribonucleic acid. On the basis of these findings, we suggest that the increase in decidual interleukin-1 beta and human leukocyte antigen HLA-DR alpha during pregnancy may be involved in maternal recognition of the fetal semiallograft and that transforming growth factor-beta production may regulate the local maternal immune response and prevent rejection of the fetus.

Blotting, Northern↗
PubMed1990

Raising expectations for grandparents: a three generational study.

Previous research resulted in the nation's first curriculum for grandparents. To determine the program benefits, 210 experimental subjects received instruction. Each of these persons chose one son or daughter and one grandchild to help evaluate changes in grandparent attitudes and behavior. All three generations completed separate versions of the Grandparent Strengths and Needs Inventory prior to the classes, at the end of intervention, and three months later. Posttesting of grandparents revealed significant improvement. These gains were corroborated by parents and grandchildren. Multivariate analyses identified the impact of eleven independent variables on grandparent performance. A control group of 185 subjects made no improvement.

Adolescent↗
PubMed1989

Grandparents and learning.

The educational needs of grandparents have been overlooked. They deserve access to a curriculum that can help them adjust to their changing role and illustrate how to build satisfying family relationships. In order to identify appropriate topics and instructional procedures for grandparent education, weekly meetings were held for a semester with 400 grandmothers and grandfathers. The resulting program includes experiences in sharing feelings and ideas with peers; listening to the views of younger people; studying lifespan growth and adjustment; acquiring intergenerational communication skills; and focusing self-evaluation. A fieldtest involving several hundred participants, equally divided into experimental and control groups, is underway to determine the worthwhileness of this approach to family development.

Age Factors↗
PubMed1989

Epstein-Barr virus-associated lymphoproliferative disorder. Applications of immunoperoxidase and molecular biologic techniques.

A 17-year-old boy with fever and cervical lymphadenopathy developed multiple-organ failure and died three weeks after hospital admission. A lymph node biopsy specimen demonstrated a florid immunoblastic infiltrate that was suspicious for a malignant lymphoma. By using immunoperoxidase and molecular biologic techniques, evidence was presented for an Epstein-Barr virus-associated lymphoproliferative disorder.

Adolescent↗
PubMed1986

Cytotoxic studies in human newborns: lessened allogeneic cell-induced (augmented) cytotoxicity but strong lymphokine-activated cytotoxicity of cord mononuclear cells.

Nonspecific cytotoxic responses such as natural killer activity can be increased in vitro by incubating effector cells with soluble factors or allogeneic cells. We sought to determine if newborn cells, known to be deficient in most cytotoxic responses, including resting NK activity, could develop enhanced cytotoxic responses following incubation with allogeneic cells (augmented cytotoxicity) or with lymphokines (lymphokine-activated cytotoxicity). Cord whole mononuclear cells (WMC) incubated with irradiated Raji cells for 5 days develop lower levels of cytotoxicity toward K562 targets at both a 20:1 effector:target (E:T) ratio (39 +/- 2.7% vs 49 +/- 3.6%) and a 10:1 E:T ratio (29 +/- 2.6% vs 40 +/- 3.6%) than do adult cells. Lessened specific cytotoxicity of cord cells developed toward the sensitizing Raji cells was also observed at both E:T ratios. Attempts to enhance the induced cytotoxicity by incubation with interferon or isoprinosine were unsuccessful. In contrast, lymphokine (i.e., interleukin 2)-activated killer (LAK) cytotoxicity is not deficient in cord WMC. Indeed, the level of LAK cytotoxicity is equivalent to that observed with similarly treated adult cells despite a lower baseline level of cytotoxicity toward the target cells. In the presence of purified IL-2 for 5 days, cord WMC cytotoxicity against K562 cells increased from 12 +/- 2.6 to 71 +/- 4.2% and against Raji cells increased from 9.6 +/- 2.5 to 48 +/- 6.7%. Similarly treated adult cells increased their killing against K562 from 23 +/- 4.2 to 61 +/- 4.5% and against Raji from 12 +/- 3.0 to 36 +/- 5.3%. This substantial lymphokine-activated cytotoxicity of newborn cells suggests the possibility of therapeutic intervention with purified lymphokines in neonatal infections or neoplasms.

Cytotoxicity, Immunologic↗
PubMed1986

Assessment of unscheduled and replicative DNA synthesis in hepatocytes treated in vivo and in vitro with unleaded gasoline or 2,2,4-trimethylpentane.

In a recent chronic inhalation exposure study, unleaded gasoline (UG) produced kidney tumors in male rats and liver tumors in female mice, but did not increase the incidence of liver tumors in male mice or rats of either sex. To examine the possible basis for this pattern of hepatocarcinogenesis, unscheduled DNA synthesis (UDS) as an indicator of genotoxic activity and replicative DNA synthesis (RDS) as an indicator of cell proliferation were measured in rat and mouse hepatocytes following in vivo and in vitro exposures to UG and 2,2,4-trimethylpentane (TMP), a nephrotoxic component of UG. Primary hepatocyte cultures, prepared from cells isolated from Fischer-344 rats, B6C3F1 mice, or human surgical material, were incubated with [3H]thymidine and the test agent. UDS was measured by quantitative autoradiography as net nuclear grains (NG). By similar methods, UDS and RDS (S-phase cells) were measured in hepatocytes isolated from rats and mice treated by gavage with TMP (500 mg/kg) or UG (100 to 5,000 mg/kg). A dose-related increase in UDS activity was observed in rat hepatocytes treated in vitro with 0.05 to 0.10% (v/v) UG. These doses were, however, toxic in both mouse and human hepatocyte cultures. Weak UDS activity was observed in hepatocytes isolated from male and female mice treated 12 hr previously with UG. No UDS was induced in rat hepatocytes treated in vivo or in vitro with TMP. Twenty- and fourfold increases in the percentage of cells in S-phase were observed 24 hr after treatment with TMP in male and female mice, respectively, as compared to a fivefold increase in male rats. UG increased the percentage of S-phase cells in male mice by ninefold but failed to induce RDS in females. Thus, there appears to be genotoxic compounds in UG that can be detected in cultured hepatocytes and in the livers of exposed mice. The lack of UDS activity in rat liver was consistent with the reported lack of liver tumors in chronically exposed rats. However, neither the UDS nor the RDS responses in mice exposed by gavage correlated to the sex-specific pattern of liver tumors observed in the 2-year bioassay.

Animals↗
PubMed1984

Lack of genotoxic activity of di(2-ethylhexyl)phthalate (DEHP) in rat and human hepatocytes.

Di(2-ethylhexyl)phthalate (DEHP) is a widely used plasticizer which has been reported to induce a statistically significant increase in the incidence of hepatocellular carcinomas in female Fischer-344 rats (8/50) when administered in the diet at 12 000 p.p.m. for two years. Numerous studies with cells in culture have failed to show any genotoxic activity associated with DEHP. Because DEHP induces multiple changes in the liver, such as peroxisomal proliferation, it was possible that these alterations could result in genotoxic effects in the treated whole animal that would not be seen in cells in culture. Accordingly, the ability of DEHP to induce DNA damage or repair was examined in rat hepatocytes in vivo and in vitro and in human hepatocytes in vitro. Unscheduled DNA synthesis was measured by incorporation of [3H]thymidine into primary hepatocyte cultures immediately isolated from treated animals or hepatocyte cultures incubated directly with DEHP. DNA damage was measured by alkaline elution of cellular DNA from the same cultures. In vivo-in vitro treatment regimens were: (i) female rats, 12 000 p.p.m. DEHP in the diet for 30 days; (ii) female rats, 12 000 p.p.m. in the diet for 30 days, followed by 500 mg/kg DEHP by gavage 2 h before sacrifice; (iii) male rats, 500 mg/kg DEHP by gavage 2, 12, 24, or 48 h before sacrifice; and (iv) male rats, 150 mg/kg/day by gavage for 14 days. In vitro conditions were 0.1, 1.0 and 10.0 mM DEHP in the cultures for 18 h. Primary cultures of human hepatocytes were prepared from freshly discarded surgical material and exposed to the same concentration of DEHP. Concentrations up to 0.5 mM mono(2-ethylhexyl)phthalate, a principal metabolite of DEHP, were also examined in the human hepatocyte assay. No chemically induced DNA damage or repair was observed in vivo or in vitro in rat or human hepatocytes under any of the conditions employed. However, an increase in the percentage of cells in S-phase in the animals given DEHP was observed. These data indicate that DEHP does not exhibit direct genotoxic activity in the animals even with a treatment regimen which eventually produced tumors in a long term bioassay, and that both rat and human hepatocytes are similar in their lack of a genotoxic response to DEHP exposure in culture.

Animals↗
PubMed1983

Induction of DNA repair in human and rat hepatocytes by 1,6-dinitropyrene.

1,6-Dinitropyrene (DNP) was found to be an extremely potent genotoxicant in metabolically competent primary cultures of human and rat hepatocytes. Dose-dependent increases in DNA repair as measured by unscheduled DNA synthesis (UDS) were observed in the range from 0.05 to 5 microM 1,6-DNP for both species, indicating that the rat-hepatocyte assay is an appropriate model for assessing genotoxic potential in human hepatocytes for this class of compound. Unlike some nitroaromatic compounds, 1,6-DNP did not require gut flora for metabolic activation. No DNA repair was observed in hepatocytes isolated from rats treated with 50 mg/kg 1,6-DNP in corn oil by gavage 2, 12 or 24 h previously. The reason for the lack of a response in vivo is not known, but may relate to detoxification or distribution of the compound in the animal.

Animals↗
PubMed1982

Mutagenesis and DNA binding of benzo(a)pyrene in cocultures of rat hepatocytes and human fibroblasts.

The genotoxicity of benzo(a)pyrene (BP) was investigated in combined cultures of rat hepatocytes and human diploid fibroblasts. Freshly isolated rat hepatocytes were shown to activate BP to a species which bound to and damaged hepatocyte and fibroblast DNA. A significant increase in the hypoxanthine-guanine phosphoribosyltransferase mutation frequency was induced when 10 to 100 microM BP was added to the cocultures. A comparative analysis of the binding of BP metabolites to hepatocyte and fibroblast DNA revealed that approximately 4 times more [3H]BP metabolites were bound to the fibroblast DNA than were bound to the hepatocyte DNA (per microgram DNA). Activation of BP by the fibroblasts themselves was shown not to be the cause of the relatively greater binding of BP to fibroblast DNA than to the hepatocyte DNA. These results suggest that proximate and/or ultimately carcinogenic metabolites of BP are readily released from isolated hepatocytes and that the metabolites are sufficiently stable and long lived so as to bind to the DNA of an adjacent cell. The relative protection of the hepatocytic DNA from BP metabolites that generated in the cytoplasm of the hepatocyte may be significant in view of the observations that the liver is not under normal conditions a target of BP carcinogenicity in vivo.

Animals↗
PubMed1981

Comparisons of the effects of chemical carcinogens in mixed cultures of rat hepatocytes and human fibroblasts.

Unscheduled DNA synthesis (UDS) was measured simultaneously in rat hepatocytes and human fibroblasts when combined cultures of the 2 cell types were exposed to procarcinogens. Human fibroblasts were preincubated with 5-bromo-2'-deoxyuridine (BRdU) to substitute for thymidine in the DNA. Hepatocyte DNA was separated from the heavier BRdU-substituted fibroblast DNA by isopycnic centrifugations in neutral cesium chloride and the specific activities of the DNA's were determined. In the presence of hepatocytes, benzo - [a]pyrene (BP) induced more UDS in the fibroblasts than in the hepatocytes. BP induced no UDS in the fibroblasts in the absence of hepatocytes. Diethylnitrosamine (DEN) and 2-acetylaminofluorene (AAF) stimulated a significant amount of UDS only in the hepatocytes. Thus, the co-cultures of hepatocytes and fibroblasts responded with UDS to these chemical carcinogens in a manner that parallels the tissue specificity of the carcinogenicity of these chemicals in vivo. That is, the known hepatocarcinogens DEN and AAF, only stimulated significant UDS in the hepatocytes, whereas the non-hepatocarcinogen, BP, though activated in these cultures mainly by the hepatocytes, stimulated more UDS in the fibroblasts than in the hepatocytes. The amount of [3H]BP bound to DNA was investigated in the co-cultures and in cultures of fibroblasts alone. When co-cultures were exposed to [3H]BP the fibroblast DNA had approximately 3 times more BP bound to it (per microgram DNA) than did the hepatocyte DNA. The amount of [3H]BP bound to the DNA of cultures of fibroblasts alone was 29% of the amount bound to the DNA of the fibroblasts from the co-cultures. Thus, although the hepatocytes were mainly responsible for the activation of BP, more [3H]BP was bound to the fibroblast DNA. It is suggested that the intercellular distribution of carcinogenic metabolites may be a significant determinant of the carcinogenic effect.

2-Acetylaminofluorene↗
PubMedDate not supplied

ADME transcriptome in Hispanic versus White donor livers: evidence of a globally enhanced NR1I3 (CAR, constitutive androstane receptor) gene signature in Hispanics.

Previous studies have found that, compared with Whites, Hispanic donor livers had elevated expression of CYP2 enzymes, gene products regulated by the constitutive androstane receptor (CAR). The objectives of the current study were to determine (1) the CAR activation signature in human liver (2) whether other drug detoxification (absorption, distribution, metabolism and excretion (ADME)) genes were differentially expressed in Hispanic versus White livers, and (3) the extent of overlap in the CAR and Hispanic liver transcriptomes. The CAR transcriptome (ADME genes differentially expressed following phenobarbital versus vehicle treatment of human hepatocytes) and the Hispanic liver transcriptome (ADME genes differentially expressed in Hispanic versus White livers) were identified using Affymetrix oligonucleotide arrays. Quantitative real-time polymerase chain reaction (PCR) was used to verify candidate genes in a larger sample size. Comparison of the CAR and Hispanic liver ADME transcriptomes revealed a significant association between the gene changes. Sixty-four per cent of the ADME genes induced more than twofold by phenobarbital were also induced in Hispanics, and 14% of the ADME genes repressed more than twofold by phenobarbital were repressed in Hispanics. In conclusion, compared with Whites, Hispanic donor livers have increased expression of many genes that are transcriptionally regulated by CAR. This result has practical implications to the drug treatment of Hispanic patients.

Adolescent↗
PubMedDate not supplied

Strengths and needs of black grandparents.

This study was conducted to identify ethnic differences in grandparent performance and effectiveness so that an educational program called Becoming A Better Grandparent could be adapted to maximize its relevance for Black families. MANOVA procedures were used to compare perceptions of 204 Anglo grandparents and 204 Black grandparents as well as 175 Anglo and 295 Black grandchildren. Black grandparents perceived themselves more favorably than did Anglos on every subscale of the Grandparent Strengths and Needs Inventory. Black grandchildren assigned grandparents significantly more favorable ratings for teaching and overall success, whereas Anglo grandchildren assigned their grandparents higher scores for coping with difficulty, managing frustration, and meeting information needs. Analyses of grandparent responses revealed significant main effects for age of grandparent, age of grandchild, time spent together, and geographical proximity. Grandchildren responses yielded significant main effects for age of grandchild and time spent together. Findings showed interaction effects for ethnicity by age of grandparent, ethnicity by age of grandchild, and ethnicity by distance. Implications for modifying the program to fit Black grandparents were identified.

Aged↗