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Biomedical subjects

L Kaminsky

Publications and source records attributed to L Kaminsky.

16 recordsLinked to original sources
PubMed2001

Siblings relationships of children with autism.

This study investigated sibling relationships of children with autism compared to children with Down syndrome and siblings of normally developing children. Ninety siblings (30 per group) between the ages of 8 and 18 participated in this study. Results indicated that sibling relationships in families of children with autism were characterized by less intimacy, prosocial behavior, and nurturance than those of the two comparison groups. Both siblings of children with autism and siblings of children with Down syndrome reported greater admiration of their sibling and less quarreling and competition in their relationships relative to normally developing comparison children.

Adaptation, Psychological↗
PubMed2000

Human cytochrome P-450 metabolism of retinals to retinoic acids.

Retinoic acids have important pleiotropic biological effects and thus the potential for human cytochrome P-450s (CYPs) to mediate retinoic acid synthesis was investigated. We examined the retinoic acid synthetic activity of human cDNA-expressed CYP1A1, 1A2, 1B1, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, 3A4+ cytochrome b(5) (b(5)), 3A5, and 4A11, expressed individually in insect cells together with NADPH-P-450 reductase. Only CYP1A1, 1A2, 1B1, and 3A4+b(5) converted all-trans-retinal (20 microM) to all-trans-retinoic acid with turnover numbers of 0.53, 0.18, 0.20, and 0.41 nmol/min/nmol P-450, respectively. With 9-cis-retinal as substrate, CYP1A2 exhibited a turnover number of 1.58 nmol/min/nmol P-450 whereas CYP1A1, 2C19, and 3A4+b(5) had turnover numbers of 0.40, 0.27, and 0.41 nmol/min/nmol P-450, respectively. For CYP3A4 activities with both retinals, b(5) was required. Kinetic analyses revealed that CYP1A1, 1A2, and 3A4+b(5) with all-trans-retinal had apparent K(m) values of 55, 356, and 255 microM, and V(max) values of 2.0, 8.3, and 6.3 nmol/min/nmol P-450, respectively, and with 9-cis-retinal had K(m) values of 77, 91, and 368 microM, and V(max) values of 2.7, 9.7, and 7.6 nmol/min/nmol P-450, respectively. The 9-cis retinoic acid synthetic activity of a group of 12 human liver microsomes correlated only with the CYP1A2 activity (r = 0.96), implicating CYP1A2 in human liver microsomal metabolism of 9-cis- retinal to 9-cis-retinoic acid. These studies have indicated that human CYPs are capable of catalyzing retinal to retinoic acid metabolism, but the physiological relevance of this metabolism is still unclear.

Animals↗
PubMed1997

Induction of CYP1A1 by beta-naphthoflavone in IEC-18 rat intestinal epithelial cells and potentiation of induction by dibutyryl cAMP.

We have examined the inducibility of CYP1A1 by beta-naphthoflavone (BNF) in a rat intestinal epithelial cell line, IEC-18, and the associated interaction between cAMP and BNF. CYP1A1 was not constitutively expressed in IEC-18 cells. Upon treatment with BNF, CYP1A1 RNA, protein, and microsomal 7-ethoxyresorufin O-deethylase activity were detected. Treatment with dibutyryl cAMP resulted in a 2-fold increase in the extent of induction at both RNA and protein levels, with corresponding increases in CYP1A1 enzymatic activity. These results support the involvement of protein kinase A in Ah receptor-mediated induction of CYP1A1 and provide an in vitro model for further studies on the mechanisms underlying regional and cellular differences in the regulation of CYP1A1 gene expression in the small intestine.

Animals↗
PubMed1997

Regulation of cytochrome P4501A1 expression in rat small intestine.

The predominant inducible cytochrome P450 (CYP) in rat small intestine is CYP1A1, which, when induced to elevated levels by xenobiotics or dietary constituents, has the potential to metabolize and consequently reduce the systemic uptake of low concentrations of orally ingested, bioactivatable polycyclic aromatic hydrocarbons and heterocyclic aromatic amines. We investigated the regulation of small intestinal CYP1A1 in an effort to develop its anticancer potential. The time courses of hepatic and intestinal CYP1A1 induction by beta-naphthoflavone (BNF) were compared quantitatively at the protein and mRNA levels by immunoblot and competitive RNA-polymerase chain reaction analyses. CYP1A1 mRNA levels in both organs increased sharply and were maximal at approximately 6 hr and returned to near basal levels by 12 hr after BNF treatment. In contrast, hepatic CYP1A2 mRNA levels increased much more gradually. Small intestinal CYP1A2 mRNA concentrations were insufficient to support translation of detectable protein. Maximal levels of intestinal and hepatic CYP1A1 protein occurred between 12 and 24 hr, and 24 and 48 hr, respectively, after BNF. Intestinal CYP1A1 protein was detectable earlier and for a shorter duration than hepatic CYP1A1. CYP1A1 induction was first detected in crypt cells 3 hr before the appearance of activity in villous cells, and maximal levels of activity were reached in crypt cells 12 to 18 hr before maximal and 1.5-fold (per mg protein) higher responses in villous cells-induction thus occurs in both villous and crypt cells. Previously detected decreases in CYP1A1 inducibility from duodenum to ileum correlated with decreases in immunoblot determined-Ah receptor levels. Intestinal CYP1A1 induction does not involve the glucocorticoid receptor in contrast to hepatic induction. These studies have revealed several novel features of small intestinal CYP1A1 regulation.

Animals↗
PubMed1997

Self-directed work teams: an 18-month review.

Visionaries are individuals who imagine how the ideal practice should be setup. Realists view practices the way they are actually setup. To bring these individuals together toward a common goal is what self-directed work teams can provide your practice. Components that make up a self-directed work team are reviewed.

Decision Making, Organizational↗
PubMed1996

Characterization of rat small intestinal cytochrome P450 composition and inducibility.

The composition and inducibility of cytochrome P450 (P450) in rat small intestinal epithelial cells were investigated with the use of RNA-polymerase chain reaction and immunoblot techniques. The complement of intestinal P450s is more restricted than hepatic forms. P450s 1A1, 2B1, and 3A1 were detected in enterocytes of untreated rats and were inducible by beta-naphthoflavone (BNF), phenobarbital, and pregnenolone-16alpha-carbonitrile or dexamethasone, respectively. In addition, P450s 2C6 and 2C11 were both constitutively expressed at low levels. In contrast, several P450 forms, which are found in the liver, were not detected in enterocytes of untreated or induced rats, including P450s 2A1, 2B2, 2E1, 3A2, and 4A1. P4501A2 mRNA was detected only in BNF-induced rat small intestine and at levels that did not result in its detectable translation. The most prominent inducible form in rat small intestine is P4501A1. Its inducibility diminishes markedly along the length of the small intestine from the duodenum to the ileum. Furthermore, the induction of P4501A1 in enterocytes was affected by the route of administration of the inducing agent. Thus, intestinal P4501A1 was more sensitive to orally administered BNF, whereas induction of hepatic P4501A1 was more sensitive to intraperitoneal administered BNF. Overall, the results demonstrate the differential regulation of P450s between the liver and small intestine, and provide a basis for further studies in assessing the potential of intestinal P450s to protect against orally ingested polycyclic aromatic hydrocarbon carcinogens.

Animals↗
PubMed1986

Calculation of 2,3,7,8-TCDD equivalent concentrations of complex environmental contaminant mixtures.

Sufficient toxicological data are now available to permit use of conventional risk assessment techniques to estimate the hazards associated with human exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). However, many real-world exposures involve complex mixtures of dibenzodioxins, dibenzofurans, and related compounds. Historical approaches to risk assessment on such mixtures have ranged from ignoring all compounds except 2,3,7,8-TCDD itself to assuming that all compounds have potencies equal to 2,3,7,8-TCDD. An alternative approach which uses existing literature data and analytical results to calculate the "2,3,7,8-TCDD equivalent" concentration of a mixture in order to "predict" its biological potency relative to 2,3,7,8-TCDD itself is advanced here. Previously reported in vivo acute and subchronic studies and some recently obtained analytical chemistry data are integrated here to clarify the utility of this important approach and to assess the uncertainties associated with its use. This predictive approach, and various conceptually similar ones, have now found wide applicability to the risk assessment process associated with exposure to complex mixtures of dioxins, dibenzofurans, and related compounds.

Alanine Transaminase↗
PubMed1985

Isolation of AIDS-associated retroviruses from cerebrospinal fluid and brain of patients with neurological symptoms.

Acquired-immunodeficiency-syndrome (AIDS)-associated retroviruses (ARV) have been isolated from the cerebrospinal fluid and brain of homosexual men presenting with neurological symptoms. Most of these patients also met the clinical criteria for AIDS. The viruses grew readily in peripheral mononuclear cells and were identified by their induction of cytopathic effects and ARV antigens in culture. The results suggest that ARV could be the cause of the neurological syndromes in AIDS patients and indicate that the virus can infect cells other than T lymphocytes.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Antibodies to AIDS-associated retrovirus distinguish between pediatric primary and acquired immunodeficiency diseases.

Antibody to acquired immunodeficiency syndrome (AIDS)-associated retroviruses (ARVs) was investigated in 68 pediatric patients with abnormalities of T-cell and/or B-cell immunity. All except seven patients conformed to a specific World Health Organization classification for immunodeficiency disease. These seven patients had polyclonal hypergammaglobulinemia and T-cell immunodeficiency. Six of the seven patients had antibody to ARV and had risk factors associated with AIDS. The one patient without antiviral antibody had no AIDS risk factors. No antibody was detected in 61 patients with other primary immunodeficiency disorders. We conclude that ARV first appeared in our population of immunodeficient pediatric patients prior to 1978, is associated with a distinctive immunologic phenotype consisting of polyclonal hypergammaglobulinemia and T-cell immunodeficiency, and does not appear as an opportunistic infection in other immunodeficiency disorders. Detection of the retrovirus associated with AIDS is of value in identifying infants and children who may have unique medical and social problems that occur with AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Trifluorinated ether anesthetic lethality in rats: the role of bacterial infection.

The lethal effects of the fluorinated ether anesthetics fluroxene (2,2,2-trifluoroethyl vinyl ether) and its ethyl (TFEE) and allyl analogues in male Wistar rats have previously been demonstrated to be potentiated by specific hepatic microsomal cytochromes P-450, and mediated by the common metabolite 2,2,2-trifluoroethanol (TFE). We report here that administration of lethal combinations of anesthetic and cytochrome P-450-inducing agents or of lethal doses of TFE (0.21 g/kg and higher) to rats caused decreased white blood cell counts, necrosis of sternum bone marrow cells and lymphocytes in the thymic cortex, and resulted in Escherichia coli contamination of the blood, lungs, liver, and kidneys of treated rats. Control animals in identical environments were free of bacterial contamination. Pretreatment of rats with the antibiotic tetracycline-HCl in the drinking water (0.6 g/liter) from 24 hr before anesthetic or TFE administration significantly diminished the mortality. With TFEE and beta-naphthoflavone induction, mortality was reduced from 85 to 30% by the antibiotic. However, the antibody plaque assay following immunization with sheep erythrocytes indicated that the primary humoral immune response to a thymus-dependent antigen was not impaired in treated rats. These results considered together indicate that metabolic formation of TFE from the anesthetic agents produced a decreased host resistance with subsequent increased susceptibility to bacterial infection. If not administered the antibiotic, the animals succumbed to the infection.

Anesthetics↗
PubMedDate not supplied

Fluroxene (2, 2, 2-trifluorethyl vinyl ether) toxicity: a chemical aspect.

Fluroxene is highly toxic to several animal species. This toxicity is enhanced by induction of raised levels of hepatic microsomal enzymes. Experiments in rats are described which seek to assess the rleative contribution to this toxicity of the individual component groups of the fluroxene molecule. Though results point to the trifluoroethyl moiety of fluroxene as that aspect of the molecule most responsible for the observed mortality, reduction of the vinyl group modifies the pattern of liver injury. That the liver necrosis, manifest following fluroxene anesthesia in the presence of microsomal induction, is alone the direct cause of the acute death of experimental animals is questioned.

Animals↗