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J S Fine

Publications and source records attributed to J S Fine.

At least 37 records · Page 2Linked to original sources
PubMed1992

Update in medical toxicology.

This article examines some current issues in toxicologic care. First there is a review of the scope of pediatric poisonings and some aspects of initial management. Then there is a discussion of the decision-making process required to properly use gastric decontamination in the management of poisonings. Each of the common methods available--emesis, gastric lavage, activated charcoal, catharsis, and whole bowel irrigation--is discussed. Finally, several new and old antidotes are reviewed, namely naloxone, glucagon, bicarbonate, dimercaptosuccinic acid, digoxin-specific fab fragments, and flumazenil.

Antidotes↗
PubMed1992

Changes in the methylation pattern of the TCR zeta-chain gene correlate with its expression in T cells and developing thymocytes.

The tight regulation of T-cell gene expression during thymic ontogeny is essential to the development of a normal immune system. One set of developmentally regulated genes encodes the multicomponent T-cell antigen receptor (TCR). The zeta chain, a component of the TCR, has been shown to play important roles in signal transduction from antigen binding to T-cell activation and in transport of the TCR complex to the cell surface. In this study, we examine the regulation of zeta gene expression in murine T-cell hybridomas. In these cells, zeta expression is correlated with complex, but predictable, changes in the pattern of cytosine methylation of its gene. Some of these structural changes are identical to those observed in murine fetal thymocytes and correlate with the rapid alteration of zeta message seen in the thymus between days 15 and 18 of gestation.

Animals↗
PubMed1991

The role of LFA-1/ICAM-1 interactions during murine T lymphocyte development.

We have examined the expression and function of the cell adhesion molecules LFA-1 (CD11a/CD18), ICAM-1 (CD54), and ICAM-2 in murine fetal thymic ontogeny and in the adult thymus. On fetal days 14 and 15, 40 to 50% of thymocytes coexpress high levels of LFA-1 and ICAM-1, as determined by flow cytometry. By day 16, more than 90% of fetal thymocytes are LFA-1+ ICAM-1hi, and all IL-2R+ cells are located in this population. Although LFA-1 expression remains unchanged thereafter, ICAM-1 expression appears to be differentially regulated in different thymocyte subpopulations, with CD4+8+ cells being ICAM-1lo and CD4-8- thymocytes remaining ICAM-1hi. ICAM-2 surface expression is dull on both fetal and adult thymocytes. Surprisingly, the expression of ICAM-1 is differentially up-regulated on T cells having a mature phenotype in thymus and in peripheral lymphoid organs, with CD8+ T cells bearing the highest amount of surface ICAM-1. Addition of anti-ICAM-1 or anti-LFA-1 antibodies to fetal thymic organ cultures results in the impaired generation of CD4+8+ cells. These results indicate that LFA-1/ICAM-1 interactions facilitate murine thymic development and suggest that cell adhesion molecules mediate important events in T cell differentiation.

Age Factors↗
PubMed1990

Impairment of prothymocyte activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Exposure of experimental animals to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in severe thymic atrophy and suppression of cell-mediated and humoral immune functions. However, despite much effort the mechanism by which TCDD produces these responses, particularly thymic atrophy, remains unclear. In this report, we have examined the effect of acute TCDD exposure on lymphocyte stem cells in young adult BALB/c mice to determine whether alterations to events early in T lymphopoiesis contribute to TCDD-induced thymic atrophy. TCDD produced a dose-dependent reduction in thymic weight and cellularity following a single dose of 5 to 120 micrograms TCDD/kg. This thymic atrophy correlated with a dose-dependent suppression of the biosynthesis and mRNA levels of the lymphocyte stem cell-specific DNA polymerase terminal deoxynucleotidyl transferase in bone marrow and thymus. However, the reduction in thymic terminal deoxynucleotidyl nucleotidyl transferase synthesis, on a per cell basis, was less than that observed in bone marrow. Intrathymic CD4/CD8 and IL-2R expression demonstrated only mild alterations after exposure to 30 micrograms TCDD/kg. These data suggest that thymocytes are more refractory to TCDD than are pre-T cells. To assess this possibility directly, bone marrow prothymocytes from TCDD-treated donor mice were examined for their capacity to reconstitute the thymuses of adoptive, irradiated recipients. Our results indicate that prothymocyte activity was severely impaired by TCDD exposure and that this effect occurred at low tissue levels of TCDD. In contrast, we observed no reduction in the number of colony-forming unit-granulocyte macrophage and a moderate decrease in colony-forming unit-spleen. These data suggest that TCDD-induced thymic atrophy is the result, at least in part, of impaired thymic seeding by prothymocytes.

Animals↗
PubMed1990

Prothymocyte activity is reduced by perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

The mechanism by which exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces thymic atrophy and cell-mediated immune suppression in experimental animals is poorly understood. A previous study from our laboratory found that terminal deoxynucleotidyl transferase-synthesizing lymphocyte stem cell populations in fetal liver and neonatal bone marrow, but not thymus, were profoundly altered after perinatal TCDD exposure, implying that a defect in the prothymocyte population in liver and marrow may play a role in the etiology of thymic atrophy in TCDD-exposed animals. In this report, we present results of experiments designed to directly assess the prothymocyte compartment in mice exposed to TCDD perinatally by examining the ability of these stem cells to reconstitute an irradiated thymus. Maternal TCDD exposure (15 micrograms/kg) caused a significant impairment of both fetal liver and neonatal bone marrow prothymocyte activity. These alterations occurred at tissue concentrations less than 200 fg of TCDD per mg. TCDD treatment also resulted in a mild reduction in colony-forming unit-spleen in these organs and a decrease in colony-forming unit-granulocyte-macrophage in fetal and neonatal liver, but not bone marrow. Overall, these data provide evidence that alterations to early stages of T-lymphopoiesis, at the level of the prothymocyte, may be involved in the development of TCDD-induced thymic atrophy and cell-mediated immunosuppression.

Animals↗
PubMed1989

Lymphocyte stem cell alterations following perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Perinatal exposure of experimental animals to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) leads to thymic atrophy and a suppression of cell-mediated immunity that is more severe and persistent than that caused by adult exposure, suggesting that events involved in the maturation of the immune system are particularly sensitive to TCDD. We report here that perinatal TCDD exposure produces an alteration in the lymphocyte stem cell population in the fetus and neonate, as evidenced by a significant reduction in the lymphocyte stem cell-specific enzyme terminal deoxynucleotidyl transferase (TdT). After maternal treatment with a single dose of TCDD (10 micrograms/kg of body weight) on gestational day (gd) 14, TdT biosynthesis and TdT-specific mRNA were reduced more than 50% in fetal liver lymphoid cells on gd 18. An even more extensive reduction was seen in neonatal bone marrow through postnatal day 18. In contrast, thymic TdT synthesis appeared to be relatively unaffected on a per cell basis by perinatal TCDD exposure, although the actual number of TdT-synthesizing thymocytes was diminished due to extensive thymic atrophy. These effects occurred at concentrations of 1-31 fg of TCDD/mg of thymus. Flow cytometric analysis of thymocyte surface marker expression revealed a slight decrease in the percentage of Lyt-2+L3T4+ thymocytes on gd 18 and postnatal day 4. This alteration was no longer apparent by postnatal day 11, when marrow TdT biosynthesis was most suppressed. These results suggest that TCDD-induced thymic atrophy during the perinatal period may be due, in part, to an effect on the prothymocyte.

Animals↗
PubMed1988

Regional creatine kinase, adenylate kinase, and lactate dehydrogenase in normal canine brain.

Following acute stroke, creatine kinase and other enzymes are released into the cerebrospinal fluid and blood from injured brain tissue. To determine whether regional differences in brain enzyme activity might exist and therefore affect the amount of enzyme released, we quantified the levels of creatine kinase, adenylate kinase, and lactate dehydrogenase in 12 regions of normal canine brain (n = 4). Adenylate kinase activity varied the least among regions (49 +/- 7 units/g), followed by lactate dehydrogenase activity (122 +/- 28 units/g). The pattern for both adenylate kinase and lactate dehydrogenase was higher activity in predominantly gray matter areas, lower activity in white matter, and intermediate activity in mixed regions. The distribution of creatine kinase brain isoenzyme and mitochondrial creatine kinase in canine brain was less predictable, showing wider variations among regions (isoenzyme, 462 +/- 116 units/g; mitochondrial, 42 +/- 20 units/g). Even cerebral gray matter demonstrated substantial regional variations in creatine kinase brain isoenzyme, ranging from 606 units/g in the parietal cortex to 329 units/g in the temporal cortex. We conclude that the content of creatine kinase brain isoenzyme varies more than twofold among areas of brain. This regional variation may be important in the interpretation of creatine kinase brain isoenzyme measurements in cerebrospinal fluid and serum used to assess neurologic injury following stroke.

Adenylate Kinase↗
PubMed1988

Survey of alpha-amylase activity and isoamylases in autopsy tissue.

We quantified total amylase and its isoenzymes in 22 different human tissues obtained at autopsy. Isoenzymes were separated by use of wheat-germ inhibition (WI) and electrophoresis on cellulose acetate (CA) and agarose (AG). Mean (+/- SD) total activity was highest in salivary glands (parotid 1710 +/- 897 U/g, submandibular 605 +/- 354 U/g), and pancreas (258 +/- 137 U/g). All other tissues contained 100- to 1000-fold less amylase. As assessed with WI, pancreas, jejunum, liver, placenta, testis, skeletal muscle, and spleen contained more than 90% pancreatic isoamylase. Salivary glands and thyroid contained more than 90% salivary isoamylase. All other tissues contained a mixture of the two isoenzymes. CA and AG often produced different results. For both CA and AG the most common pancreatic isoforms were P2 and S1. Salivary gland homogenates demonstrated a band migrating in the P3 position on CA. We conclude that both types of amylase isoenzymes can be found in tissues other than salivary gland and pancreas, but that their low total amylase concentrations diminish their clinical importance.

Electrophoresis, Polyacrylamide Gel↗
PubMed1988

Effect of creatine kinase-MM subtype composition on a CK-MB immunoinhibition assay.

Immunoinhibition (INH) by use of polyclonal anti-human CK-M antibody may be used to measure CK-MB in serum. Previous studies have shown that inhibiting antibodies prepared against purified muscle extracts may inhibit CK-MM by greater than 99%. Using patients' sera and muscle homogenates incubated with human serum, we studied the effect of CK-MM subtype composition on an INH assay. We found that with increasing time from the CK-releasing event, e.g., myocardial infarction, or with longer in vitro incubation, the proportion of CK-MM1 increased and the proportion of uninhibited CK-MM increased from 0.2% to 0.7-0.8%. As a consequence, CK-MB activity may be overestimated by as much as 1.6% of total CK when uncorrected INH results are used. Inhibition was maximal in samples containing 100% CK-MM3, the tissue subtype. Because of the time-dependent change in CK-MM subtypes, published results for INH from studies in which CK-MM purified from muscle was used may not be directly applicable to clinical specimens.

Creatine Kinase↗
PubMed1988

Three methods compared for isoamylase separation in tissue homogenates.

Using homogenates of autopsy tissue, we compared three widely available techniques for separating amylase isoenzymes: wheat-germ inhibition (WI), and electrophoresis on cellulose acetate (CA) or agarose (AG). WI separated amylase into two isoforms, CA into seven (three pancreatic and four salivary), and AG into nine (five pancreatic and four salivary). CA and WI had similar isoamylase detection limits (8-10 U/L) and similar imprecision in measuring percent S-type vs P-type isoamylase (within-run SD 1-2%), and they demonstrated a linear response to added S or P isoamylase. In contrast, the AG method had higher detection limits (10-15 U/L), greater imprecision (within-run SD 3%), and showed a nonlinear response to added S or P isomylase. We conclude that CA and WI have essentially equivalent assay attributes, superior to AG, but that CA resolves more amylase isoforms than WI.

Electrophoresis, Agar Gel↗
PubMed1987

Isoelectric focusing of neuraminidase-treated alkaline phosphatase isoenzymes on agarose gel.

We attempted to separate bone and liver alkaline phosphatase (EC 3.1.3.1) isoenzymes in human serum by isoelectric focusing on agarose gel. We found that in a pH 3-10 gradient the liver and bone isoenzymes focused into so many bands over a narrow pH range such that the information could not be quantified. However, when the bone isoenzyme in serum was first desialylated at 37 degrees C for a minimum of 6 h, catalyzed by neuraminidase (EC 3.2.1.18) at pH 5.8-6.0, we could detect four distinct bands with pls of 6.7, 6.8, 6.9, and 7.0. Under the same conditions, the liver isoenzyme in human serum focused into one band at pH 7.0. The multiple banding we observed for the desialylated bone isoenzyme has not been previously reported. The method is suited as a qualitative technique for detecting the bone alkaline phosphatase isoenzyme in serum.

Alkaline Phosphatase↗
PubMed1986

Mitochondrial and MB isoenzymes of creatine kinase in cerebrospinal fluid from patients with hypoxic-ischemic brain damage.

Measurements of cerebrospinal fluid (CSF) creatine kinase (CK, EC 2.7.3.2) isoenzyme activity have been used to predict outcome in patients with acute brain injury following cardiac arrest. We identified two CK isoenzymes previously unreported in CSF from 16 patients with hypoxic-ischemic brain damage. Prior to analysis, the CK in the CSF samples was reactivated with dithiothreitol. CK isoenzymes were identified using electrophoretic and immunologic methods. Total CK activity ranged from 23 to 924 U/L (mean 452). CSF-CK-BB was the predominant isoenzyme present in all cases. In addition to CSF-CK-BB, the authors identified CSF-CK-MM in 6 cases, CSF-CK-MB in 8 cases, and CSF-mitochondrial-CK in 14 cases. The presence of CSF-CK-MM was significantly related to blood contaminating the CSF (P less than 0.02). It is proposed that CSF-CK-MB results from recombination of CK-MM and CK-BB in CSF and that mitochondrial CK is released with CK-BB into the CSF from the damaged brain tissue.

Brain↗
PubMed1985

Single-dose versus conventional therapy of urinary tract infections in female adolescents.

A randomized, prospective study was done to assess the efficacy of single-dose nu conventional treatment of acute urinary tract infection (UTI) in female adolescents. Thirty-one 12- to 18-year-old female adolescents with symptoms of an acute UTI and a urine culture with greater than 10(5) organisms were treated with amoxicillin, either as a 3.0-g single dose or 250-mg three times daily for ten days. Urine cultures obtained three days after completing therapy in each group, showed bacteriologic cure rate of 69% (11/16) with single-dose treatment compared with a cure rate of 87% (13/15) in the conventional treatment group (P = .23). When patients with resistant organisms were excluded, the cure rate was 85% in both groups. Complete symptom resolution in less than two days after commencing treatment occurred in 36% of single-dose group nu none of the patients in the conventional-dose group. The finding has not been previously reported in single-dose trials. Candida vaginitis occurred in 20% of the conventional-dose group nu none of the single-dose group. All patients in the single-dose group kept their first scheduled follow-up appointment, whereas 40% in the conventional group required reminders and rescheduling. Perfect compliance with the medication regimen was reported by 27% of the patients taking ten days of medicine. Although single-dose cure rates may not be superior to conventional-dose rates, the advantages of single-dose treatment include increased compliance with medication and follow-up, decreased side effects, and more rapid resolution of symptoms.

Adolescent↗