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Biomedical subjects

B Cornblatt

Publications and source records attributed to B Cornblatt.

At least 19 recordsLinked to original sources
PubMed1995

Susceptibility of idarubicin, daunorubicin, and their C-13 alcohol metabolites to transport-mediated multidrug resistance.

The intracellular pharmacokinetics and cytotoxicity of idarubicin (IDA), daunorubicin (DNR), and their corresponding C-13 alcohol metabolites, idarubicinol (IDAol) and daunorubicinol (DNRol), were studied in drug-sensitive HL-60/W human leukemia cells, and in two multidrug-resistant (MDR) sublines, HL-60/Vinc (overexpress P-glycoprotein, Pgp) and HL-60/Adr (overexpress multidrug resistance-associated protein, MRP). Intracellular drug accumulation (1 micrograms/mL) and retention were measured by flow cytometry. Mean intracellular steady-state concentration (Css, fluorescence units/cell) and area under the intracellular drug concentration x time curve (AUC, Fl.U/cell.min) were calculated. Relative to the values for the respective drugs in HL-60/W cells, the Css and AUC of IDA were much higher than those of DNR in the MDR cell lines, with Css and AUC of IDAol intermediate between IDA and DNR. In the MDR cell lines, the MDR modulator cyclosporine A (CsA), in concentrations of 0.3 to 30 mumol/L, caused minimal effects on 3-hr IDA accumulation, intermediate enhancement of IDAol accumulation, and greatest enhancement of DNR accumulation. The MDR cell lines were much less resistant to IDA (3- to 16-fold) than to DNR (65- to 117-fold). This difference was not the result of IDA being more potent than DNR, since the sensitivity of HL-60/W cells to IDA differed from their sensitivity to DNR by < 2-fold. The cellular pharmacokinetics and cytotoxicity of IDA in MDR human breast carcinoma cells MCF-7/AdrVp, which overexpress the putative MDR transporter P-95, were far superior to those of DNR, and were comparable to these parameters for IDA in parental MCF-7/W cells. These studies demonstrate that the cellular pharmacology and cytotoxicity of IDA in MDR cell lines that overexpress MRP, Pgp, or P-95 are more advantageous than those of DNR, suggesting that IDA is less susceptible to the transport-mediated MDR mechanism manifested. IDA is not completely invulnerable to MDR, however, since the MDR sublines studied did display a demonstrable level of resistance to IDA, compared with their drug-sensitive counterparts. IDAol, the major plasma metabolite of IDA, demonstrated behavior intermediate between the MDR-susceptible drug DNR and its parent compound, suggesting that its cytotoxic action is subject to transport-mediated cellular defenses.(ABSTRACT TRUNCATED AT 400 WORDS)

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Distractibility in schizophrenia.

This study examined the effects of neuroleptic medication on the allocation of attentional resources to distracting stimuli in patients with schizophrenia. Twenty-five patients were tested twice (medication-free and after medication stabilization) on the Identical Pairs versions of the Continuous Performance Test under both distraction and no-distraction conditions. Sixteen patients were chronically ill adults and nine patients were young neuroleptic-native patients in the early stages of illness. Results indicated that neuroleptic treatment did not improve distractibility for either group and that both groups were comparably distractible. These findings suggest that medication does not improve the misallocation of attention to distracting stimuli in patients with schizophrenia.

Acute Disease↗
PubMed1994

Synergistic reversal of multidrug-resistance phenotype in acute myeloid leukemia cells by cyclosporin A and cremophor EL.

Cremophor (Crem) EL, the vehicle for intravenous delivery of cyclosporin A (CsA), has been reported to counteract multidrug resistance (MDR) in P-glycoprotein (Pgp)-over-expressing cell lines. Because of this, we sought to determine whether Crem functions independently as a modulator of MDR in blast cells obtained from acute myelogenous leukemia (AML) patients, and the nature of its interaction in combination with CsA in reversing an MDR phenotype. In the phenotypically classical MDR AML cell lines HL-60/Vinc (overexpresses Pgp) or HL-60/AR (does not overexpress Pgp), the dose causing half-maximum enhancement (D50) of daunorubicin (DNR, 1 micrograms/mL, 3 hours) accumulation was achieved by the combination of CsA and Crem (CsA/Crem) at 1.2 mumol/L CsA. In contrast, the D50 for Crem alone was approached at an amount that would be needed to suspend 6.2 mumol/L CsA for HL-60/Vinc, and 81 mumol/L CsA for HL-60/AR. The D50 concentrations for CsA alone (dissolved in ethanol, which does not alter DNR accumulation) were also higher than those for CsA/Crem, being 6.5 mumol/L for HL-60/Vinc, and 3.1 mumol/L for HL-60/AR. The maximum absolute level of enhancement of DNR accumulation (Emax) in each cell line was approximately equivalent for CsA/Crem or CsA alone, and was equal to the 3 hr intracellular DNR accumulation observed in parental, drug sensitive HL-60/W cells. For Crem alone, HL-60/AR and HL-60/Vinc cells showed markedly different responses: HL-60/Vinc cells attained intracellular DNR content comparable to HL-60/W, whereas HL-60/AR cells achieved only approximately 35% of this level. Multiple-drug effects were analyzed by calculation of the Combination Index (Chou and Talalay, Adv Enzyme Regul 22:27, 1984), which indicated that CsA and Crem are synergistic in causing enhancement of DNR accumulation in these MDR HL-60 cell lines. In blasts from AML patients, 5 mumol/L CsA/Crem or an equivalent amount of Crem alone each caused significant (P < .001) enhancement of DNR accumulation (60 AML-patient marrow samples) or DNR retention (51 AML-patient marrows). Similarly, CsA/Crem or Crem alone caused significant (P < .01) enhancement of the cytotoxicity of DNR in 36 AML blast cell specimens. The degree of enhancement of accumulation/retention or cytotoxicity by CsA/Crem was approximately equivalent to that obtained with Crem alone. These studies indicate that Crem can reverse an MDR phenotype in patient AML blast cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Survival↗
PubMed1990

Report of a workshop on genetic linkage studies in schizophrenia.

A workshop on genetic linkage studies in schizophrenia was held at Columbia University's Arden House Conference Center in October 1989. This report summarizes the contents of invited talks by Drs. Arno Motulsky and T. Conrad Gilliam and the discussions at the five workshop sessions. Topics of the workshop sessions were (1) diagnostic boundaries and hierarchies in schizophrenia, (2) genetic models and linkage parameters, (3) selection and ascertainment of pedigrees, (4) future extensions of molecular genetics strategies, and (5) possibilities for future collaboration.

Genetic Linkage↗
PubMed1988

Auditory event-related potentials in children at risk for schizophrenia: the complete initial sample.

Event-related potentials (ERPs) were recorded from children of schizophrenic parents, children of parents with affective disorders, and children of parents without a history of psychiatric illness. ERPs were elicited during a modification of the "oddball" paradigm, in which two infrequents (a change in pitch and a missing stimulus) were embedded in a series of frequent background events. The data were recorded from electrodes located at midline frontal, central, parietal, and occipital scalp sites. Diagnostic assessments of the parents were performed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version (SADS-L) and Research Diagnostic Criteria (RDC). Behavioral assessments of the children were made with a modified version (BGAS) of the Global Assessment Scale. ERP amplitudes for several electrophysiological events were compared among groups for target and nontarget stimuli using analyses of of variance of both factor score and baseline to peak measures. No systematic differences suggesting waveform abnormalities in the children of schizophrenic parents (high-risk subjects) were found. However, when the results were analyzed using only those children whose parents had a "pure" diagnosis of either schizophrenia or affective disorder, the children of affectively disordered parents (psychiatric control subjects) showed significantly lower N100 amplitudes (to the frequent event only) than either the normal control or high-risk subjects. No consistent behavioral differences among the three groups emerged. Since only a small percentage of children at risk will eventually develop schizophrenia, ERP amplitude frequency distribution analyses were also performed and compared among groups. However, these did not provide evidence of an outlying subgroup in any of the three groups. There were complex relationships between ERP component amplitudes and behavioral adjustment in adolescence but, in general, these did not distinguish high-risk and psychiatric control subjects from each other. There was no evidence of a relationship between deviant attentional functioning as measured in an earlier round of laboratory testing and ERP late component amplitude.

Adolescent↗
PubMed1987

High-risk research in schizophrenia: a summary of what has been learned.

High-risk research on schizophrenia has been concerned chiefly with two types of issues: (1) description of background factors in the early lives of high-risk subjects; and (2) identification of biological variables that may be markers of the genetic liability to schizophrenic disorders. It is concluded that efforts to describe background factors have led to some conflicting results, have shown little evidence of specificity of the factors under study to risk for schizophrenia, and may not be generalizable to most individuals who develop schizophrenia. Results of research focusing on biological variables are summarized under the headings of attention and information processing (AIP), smooth pursuit eye movement (SPEM), neurological signs, electrodermal responding, event related potentials, and ventricular size. Of these, certain AIP and SPEM dysfunctions show substantial evidence of serving as biological markers, certain other AIP impairments are promising in this regard, electrodermal responsivity is not, and the other three categories present uncertain or conflicting results. Several methodological issues that have hampered the first generation of high-risk research are discussed.

Humans↗
PubMed1987

The New York High-Risk Project: a followup report.

The New York High-Risk Project began in 1971 as a prospective, longitudinal study of (1) children of one or two schizophrenic parents and (2) comparison groups of children whose parents had other or no psychiatric disorders. The former were examined because they were known to be at high risk--some 10-25 percent for children with one affected parent and 35-45 percent with two affected parents--for developing schizophrenia or schizophrenia spectrum disorders during adolescence or adulthood (Erlenmeyer-Kimling 1977; Gottesman and Shields 1982). Children of parents with affective disorders were included because we wished to determine whether variables that might differentiate the children of schizophrenic parents from the children of normal parents also differentiated them from children of parents with other psychiatric disorders. Major goals of the program were (1) identification of biological and behavioral indicators of a genetic liability to develop schizophrenia and (2) longitudinal followup of the subjects to assess the predictive validity and specificity of variables tentatively flagged as early indicators. Other goals have included evaluation of the developmental course of such variables and documentation of the history of the development of schizophrenic disorders.

Adolescent↗
PubMed1987

Toxocara canis infection of children: epidemiologic and neuropsychologic findings.

Sera from 4,652 children whose blood was submitted to the New York City Department of Health for lead analysis were tested for antibodies to Toxocara canis using an enzyme-linked immunosorbent assay (ELISA). Standardized to the age distribution of the study population, T. canis seropositivity (inverse titers greater than or equal to 16) was 5.7 per cent in males and 5.1 per cent in females. T. canis antibody titers and lead exposures as measured by Centers for Disease Control lead classes were positively correlated. Children who were seropositive to T. canis (cases) were compared to seronegatives (controls) matched on age (+/- 6 months), sex, time-of-screening (+/- 3 months) and CDC lead class. Logistic regression analysis of 155 case-control pairs demonstrated elevated relative risks (RRs) for geophagia (RR = 3.14; 95% CI = 1.75, 5.64) and having had a litter of puppies in the home (RR = 5.22; 95% CI = 1.63, 16.71). Compared to controls, cases had increased eosinophil counts, serum immunoglobulin E concentrations, and anti-hemagglutinin-A titers. Small deficits in cases compared to controls were found in performance on several neuropsychological tests after adjustment for potential confounders including case-control differences in race, socioeconomic status, and current blood lead concentrations. The study thus confirmed that T. canis infection is common in urban children and suggested that infection may be associated with adverse neuropsychological effects.

Adolescent↗
PubMed1986

Sustained attention in children at risk for schizophrenia: findings with two visual continuous performance tests in a new sample.

In partial replication of an earlier study, 35 children at high risk for schizophrenia, 25 children at high risk for affective disorder, and 53 normal control children from a new sample of 7- to 12-year-old subjects were tested with two new visual continuous performance tests. Response levels and intrasubject variability were analyzed separately. Multivariate analyses on factor scores derived from response levels indicate that "groups" is a significant predictor for a factor reflecting discriminability (or sensitivity) for the more difficult of these tests but not for the less difficult one, and that high risk for schizophrenia is associated with lower performance. Factor scores and multiple regression analyses were used to dichotomize subjects as to whether or not they are low performance outliers. A significantly larger proportion of subjects from the high risk for schizophrenia group than from the control groups were low performance outliers. Among subjects that developed psychopathology in adolescence, subjects at high risk for schizophrenia were more likely to have contributed low performance outliers early during childhood.

Adolescent↗
PubMed1986

Event-related potentials in children at risk for schizophrenia during two versions of the continuous performance test.

Event-related potentials (ERPs) were recorded from children of schizophrenic parents, children of parents with affective disorders, and children of parents without a history of psychiatric illness. ERPs were elicited during two versions of the continuous performance test (CPT), which differed in their level of processing complexity. The data were recorded from electrodes located at midline frontal, central, parietal, and occipital scalp sites. Diagnostic assessments of the parents were performed using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version and Research Diagnostic Criteria. Clinical assessments of the children were made with a modified version of the Global Assessment Scale. ERP amplitudes for six electrophysiological events were compared among groups for target and nontarget stimuli using analyses of variance of both factor score and baseline to peak measures. There was one isolated between-group finding: frontal negative slow wave recorded at FZ was of greater magnitude in the high risk (HR) than in either the psychiatric (PC) or normal control (NC) groups. Since only a small percentage of children at risk will eventually develop schizophrenia, ERP amplitude deviance and frequency distribution analyses were also performed and compared among groups. ERP component amplitudes did not distinguish the groups when each component was considered separately. Deviance analyses, using a combination of the amplitudes of the six ERP components, also did not provide evidence of a deviant subgroup within any of the three groups. There appeared to be no relationship between ERP component amplitudes and behavioral adjustment in adolescence. Some evidence of a relationship between deviant attentional functioning and ERP component amplitude was found, but the pattern of findings within the attentionally deviant HR subgroup was opposite to that found for the HR group as a whole and more consistent with the pattern found for the NC group.

Adolescent↗
PubMed1985

Electrodermal recovery data on children of schizophrenic parents.

Half-amplitude recovery of electodermal responses is compared in children of schizophrenic parents (high-risk subjects) and children of depressed or normal parents. The results are dissimilar to those reported by Mednick and colleagues on a Danish high-risk sample. No significant differences emerged among the three groups in our study. Recovery did not differ according to sex or severity of illness of the schizophrenic parent. Recoveries of high-risk subjects separated from their homes were not shorter than recoveries of subjects who remained home. Recovery time recorded in childhood was unrelated to global adjustment in adolescence.

Adolescent↗
PubMed1984

Biobehavioral risk factors in children of schizophrenic parents.

Research on risk factors for schizophrenia is reviewed with emphasis on children of schizophrenic parents. As children of schizophrenic parents are not representative of the majority of individuals who become schizophrenic, examination of variables such as those relating to home environment or parental characteristics in these children is not expected to contribute greatly to an understanding of risk for schizophrenia or to the search for early indicators of a genetic liability, whereas study of selected biobehavioral variables may do so. Four areas of biobehavioral functioning that have been examined in high-risk research are discussed. Three of these are considered to be compatible with the hypothesis of a neurointegrative defect underlying schizophrenia-proneness and to be promising for further research.

Adolescent↗
PubMed1980

Auditory recognition memory in adolescents at risk for schizophrenia: report on a verbal continuous recognition task.

As part of the New York High-Risk Project and in the context of a third round of testing, auditory short-term recognition memory for words and for consonant-vowel-consonant trigrams was measured in normal control adolescents (n = 53) and in adolescents at high risk for schizophrenia (n = 46). Differences in performance between the two groups are attributable to a lower initial memory strength on the part of the high-risk subjects, with trigrams showing larger differences than words. A subgroup of the high-risk subjects characterized by "clinical deviancy" showed, in addition, a (nonsignificant) increase in the rate of information loss from memory for trigrams.

Adolescent↗