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Biomedical subjects

R Adler

Publications and source records attributed to R Adler.

At least 55 records · Page 3Linked to original sources
PubMed1998

Comparison of treatments of persistent conduct problems in primary school children: a preliminary evaluation of a modified cognitive-behavioural approach.

OBJECTIVE: Treatment for persistent conduct problems in primary school children was developed using a modification of cognitive-behavioural therapy (MCBT). Its effectiveness was evaluated by comparing it with conjoint family therapy (FT) and eclectic therapy (ET). METHOD: Children with persistent conduct problems were randomly assigned to one of three treatment groups. They were assessed prior to treatment and then 6 months after. Measures included symptoms of the child; parents' mental health; stress of parenting; family functioning; and parental relationship. In addition, parents' and children's perception of the therapy were assessed and a treatment record was developed to track the treatment process. RESULTS: Thirty-two children were recruited for the study. No statistically significant differences were found in terms of effectiveness between the three groups. In terms of parents' perception of the therapy, there was no difference on the perception of the qualities of the therapists, but on the perception of therapy MCBT was considered to be higher in cognitive-behavioural orientation. CONCLUSION: Further research using a larger sample is required to evaluate MCBT. The study supports the idea that controlled treatment studies can be carried out within busy mental health services.

Attention Deficit and Disruptive Behavior Disorder↗
PubMed1998

Identification of two rds/peripherin homologs in the chick retina.

PURPOSE: To identify possible homologs of mammalian rds/peripherin in chick photoreceptors. METHODS: An embryonic day-15 chick retinal library was screened by polymerase chain reaction with degenerate oligonucleotide primers derived from conserved segments of the mammalian retinal degeneration slow (rds) mRNA. The resultant amplification products were used to isolate cDNAs, containing complete coding regions. These clones were studied by nucleotide sequence, Northern blot, and in situ hybridization analyses. RESULTS: Two new homologs of rds/peripherin were discovered: crds1 and crds2. The predicted crds1 protein is 78%, and the predicted crds2 protein is 54%, identical to mammalian rds/peripherin. The crds1 mRNA is an abundant 4.4-kb species present in photoreceptors. The crds2 mRNA is of similar size but is much rarer. No homologs of rom1 were identified in our screen. Developmentally, the crds1 mRNAs were first detectable at embryonic day 18. CONCLUSIONS: Crds1 likely represents the chick ortholog of mammalian rds/peripherin, whereas crds2 is a more distant homolog. Both share an elongated C-terminal domain, an unusual feature compared with other members of the rds family.

Amino Acid Sequence↗
PubMed1997

Suppression of human hepatoma in mice through adoptive transfer of immunity to the hepatitis B surface antigen.

BACKGROUND/AIMS: Adoptive transfer of immunity against hepatitis B surface antigen (HBsAg) has previously been shown to occur in mice and humans through transplantation of bone marrow cells from donors immunized against HBsAg (anti-HBs) to non-immune recipients. In the present study we evaluated the effect of adoptive transfer of immunity to HBsAg on the growth of HbsAg-secreting hepatocellular carcinoma (HCC) xenografts in athymic mice. METHODS: Immunocompetent mice were immunized with recombinant HBsAg. Bone marrow cells from anti-HBs+ mice were injected intravenously to irradiated athymic Balb/c mice which had been previously transplanted subcutaneously with Hep3B human hepatoma cells. Treatment groups included mice receiving bone marrow transplantation from HBV-immunized (anti-HBs positive) and non-immunized (anti-HBs negative) donors. RESULTS: At 9 weeks post bone marrow transplantation, tumor volume and serum alpha-fetoprotein levels in athymic mice receiving HBV-immune bone marrow cells were 11.5 mm3 and 363 ng/ml, respectively, as compared to 1579 mm3 and 19,000 ng/ml, in recipients of non-immune bone marrow transplantation (p<0.005). T-cell depletion of antiHBs+ immune bone marrow prior to transplantation decreased the anti-tumor effect but did not abolish it. A mild nonspecific, bone marrow-derived, graft versus tumor effect was observed in mice transplanted with human hepatoma cells that do not express HBsAg. CONCLUSIONS: Adoptive transfer of immunity to HBV facilitates suppression of experimental human HCC expressing HBsAg. This effect is the result of a combination of specific anti-viral surface antigen effect and a nonspecific graft versus tumor effect.

Adoptive Transfer↗
PubMed1997

Pax-6, Prox 1, and Chx10 homeobox gene expression correlates with phenotypic fate of retinal precursor cells.

PURPOSE: To study the expression patterns of the homeobox genes Pax-6, Prox 1, and Chx10 during chick retinal development in vivo and in vitro. METHODS: Sections of paraformaldehyde-fixed, paraffin-embedded eyes were obtained at a range of developmental stages. In situ hybridization was carried out on tissue sections using digoxigenin-labeled sense and antisense RNA probes that recognize chicken Pax-6 and Prox 1 (whose sequences were already available), and chicken Chx10 (which was cloned and sequenced as part of this study). Selected developmental stages were also studied by immunocytochemistry with antibodies against Pax-6 and Prox 1, and by Northern blot analysis using 32P-labeled probes. RESULTS: Until embryonic day (ED) 5, in situ hybridization shows widespread, diffuse distribution of all three genes. Between ED 6 and ED 8, however, they acquire distinct, topographically specific patterns of expression. The Prox 1 signal is predominantly expressed in the prospective horizontal cell layer of the neuroepithelium, decreases vitreally, and is absent from ganglion cells and the prospective photoreceptor layer. Pax-6 is strongly expressed only in the prospective ganglion-cell and amacrine-cell regions at the same stages, and is not detected in prospective photoreceptors. Chx10 expression becomes concentrated in the future bipolar-cell region of the inner nuclear layer. Similar patterns are maintained by ED 15 through ED 18, after cell differentiation has taken place. Pax-6 and Prox 1 immunoreactive materials showed nuclear localization and a pattern of laminar distribution equivalent to that seen by in situ hybridization. CONCLUSIONS: These results suggest that the differentiated fate of retinal precursor cells may be influenced by Pax-6, Prox 1, or Chx10, this hypothesis is now being tested using dissociated chick embryo retinal cell cultures.

Amino Acid Sequence↗
PubMed1996

The bZIP transcription factor Nrl stimulates rhodopsin promoter activity in primary retinal cell cultures.

In vitro DNA binding assays and transient transfection analysis with monkey kidney cells have implicated Nrl, a member of the Maf-Nrl subfamily of bZIP transcription factors, and the Nrl response element (NRE) in the regulation of rhodopsin expression. We have now further explored the role of the NRE and surrounding promoter elements. Using the yeast one-hybrid screen with integrated NRE and flanking DNA as bait, the predominant clone obtained was bovine Nrl. Recovery of truncated clones in the screen demonstrated that the carboxyl-terminal half of Nrl, which contains the basic and leucine zipper domains, is sufficient for DNA binding. To functionally dissect the rhodopsin promoter, transient expression studies with primary chick retinal cell cultures were performed. Deletion and mutation analyses identified two positive regulatory sequences: one between -40 and -84 base pairs (bp) and another between -84 and -130 bp. Activity of the -40 to -84 region was shown to be largely due to the NRE. On co-transfection with an NRL expression vector, there were 3-5-fold increases in the activity of rhodopsin promoter constructs containing an intact NRE but little or no effect with rhodopsin promoters containing a mutated or deleted NRE. Nrl was more effective than the related bZIP proteins, c-Fos and c-Jun, in stimulating rhodopsin promoter activity. The -84- to -130-bp region acted synergistically with the NRE to enhance both the level of basal expression and the degree of Nrl-mediated trans-activation. These studies support Nrl as a regulator of rhodopsin expression in vivo, identify an additional regulatory region just upstream of the NRE, and demonstrate the utility of primary retinal cell cultures for characterizing both the cis-acting response elements and trans-acting factors that regulate photoreceptor gene expression.

Amino Acid Sequence↗
PubMed1996

Correlations between terminal mitosis and differentiated fate of retinal precursor cells in vivo and in vitro: analysis with the "window-labeling" technique.

We have investigated with high resolution the timing of retinal precursor cell commitment to specific differentiated fates, using an in ovo modification of the in vitro "window-labeling" technique (A. M. Repka and R. Adler, J. Histochem. Cytochem. 40, 947-953, 1992a). The method involves an initial injection of tritiated thymidine into chick embryos, followed a specific number of hours later by an injection of bromodeoxyuridine (BrDU); cells born during this period are identified by being labeled with thymidine but not with BrDU. We used this method to determine, in a narrow region adjacent to the choroid fissure, the fate of cells born during defined 5-hr intervals between Embryonic Days (ED) 4-8. All the cohorts gave rise to heterogenous differentiated populations, indicating that time of cell birth is not a major cell fate determinant. A progressive restriction in the developmental potential of precursor cells, however, was suggested by the observed decrease in the number of different populations generated during each 5-hr period from ED 4 to 8, and supported also by dissociated cell culture experiments investigating the fate of cells born at different developmental stages. Microenvironmental influences were tested in vitro using cells windowed-labeled in ovo for 5 hr on ED 5. After spending at least 72 hr within the retina before their isolation for culture, these cells mimicked their in vivo fate, giving rise predominantly to nonphotoreceptor neurons; a completely different behavior was observed when the cells were isolated after shorter exposures to the retinal microenvironment, when they gave rise predominantly to photoreceptors. Together with data demonstrating that differential cell death cannot account for these results, our results are consistent with the hypothesis that cell fate determination occurs after the time of terminal mitosis.

Animals↗
PubMed1996

Mechanisms of photoreceptor death in retinal degenerations. From the cell biology of the 1990s to the ophthalmology of the 21st century?

There is still no effective treatment for retinal degenerative diseases such as retinitis pigmentosa (RP), in which the loss of photoreceptor cells causes visual loss and eventually blindness. In addition to its intrinsic scientific interest, basic research aimed at elucidating the biological mechanisms regulating the survival and function of cones and rods is also important from a clinical perspective, since it could provide a foundation for the development of therapeutic strategies for these diseases. The recent observation that photoreceptor degeneration in several RP animal models occurs through programmed cell death (apoptosis) illustrates this possibility well. This article will present a brief overview of recent research contributions toward the search for treatments for retinal degenerations of genetic origin.

Animals↗
PubMed1996

Psychosocial and family functioning in children with insulin-dependent diabetes at diagnosis and one year later.

Examined the initial impact and subsequent adjustment to the diagnosis of insulin-dependent diabetes mellitus (IDDM). Children between 1 and 14 years of age and their families were assessed several weeks after diagnosis and again a year later using standardized measures of child behavior, parental mental health, and family functioning. Immediately after diagnosis, the children and both parents exhibited mild symptoms of psychological distress but these had largely resolved at 12-month follow-up. The impact of IDDM diagnosis on family functioning varied with informant, SES, and the age of the child, with an overall tendency for families to become less flexible over the year. Findings suggest that most children and their parents exhibit satisfactory individual adjustment after a period of initial stress but family functioning is affected in complex ways. Serial follow-up of the cohort is planned to establish whether the current findings are predictive of longer term outcome.

Adaptation, Psychological↗
PubMed1996

Child Behaviour Checklist classification of behaviour disorder.

OBJECTIVE: The aim of this study was to determine the applicability of the published clinical cut-off scores of the Child Behaviour Checklist (CBCL) for the classification of behaviour disorders. METHODOLOGY: Child Behaviour Checklists were obtained for 1342 subjects newly referred to the six major mental health centres in Melbourne. The normative community sample of 1002 7-, 12- and 15-year-olds was drawn from a school-based asthma prevalence study. RESULTS: The mean total problem T-score for the children referred to mental health centres was 67 and was above the clinical range for all age groups. Using referral to psychiatric services as the gold standard, the sensitivity and specificity of the CBCL using a cut-off of > or = 60, was 77.4 and 83.2%, respectively. This compares favourably with the sensitivity of 68% and specificity of 82% for the American sample. Using a cut-off score of > or = 63, the sensitivity was 70.5% and the specificity was 88.6%. The referred and community samples differed with respect to socio-economic status, family structure and mothers' level of education. Fifty-two per cent of the clinically referred children lived with both parents, compared with 89% of the community sample. CONCLUSIONS: While there are some limitations to this study in terms of both the clinic and community sample, support is provided for the usefulness and applicability of the recommended CBCL cut-off scores in an Australian population.

Adolescent↗
PubMed1996

Development and maintenance of outer segments by isolated chick embryo photoreceptor cells in culture.

PURPOSE: To investigate the capacity of isolated chick embryo photoreceptors to develop and maintain outer-segment processes in dissociated cell cultures, in the absence of pigment epithelial and glial cells. METHODS: Cells were obtained from the retinas of embryonic day (ED) 17 chick embryos, after the onset of outer-segment formation in vivo. After 5 to 12-minute incubation in Ca++ and Mg++-free Hank's balanced salt solution, neural retinas were freed from other optical tissues, including the pigment epithelium. Retinal cell suspensions were prepared by repeated pipetting after mild trypsinization and were grown in serum-containing medium on a polyornithine-coated substratum. Cell differentiation was evaluated using phase-contrast and transmission electron microscopes and by autoradiographic analysis of the uptake of putative amino acid neurotransmitters, lectin cytochemical analysis, and immunocytochemical analysis with rod and cone-specific antibodies. Cells isolated from ED 8 retinas, before the onset of outer-segment formation in vivo, were also studied. RESULTS: At culture onset, ED 17 cells appeared morphologically undifferentiated and devoid of processes; differentiated features could be detected after 24 to 48 hours in vitro. Photoreceptor cells were the most abundant cell type after 6 days in vitro, followed by nonphotoreceptor multipolar neurons and morphologically undifferentiated cells. Autoradiographic analysis showed extensive Na+ -dependent uptake of (2,3,4-(3)H)gamma- aminobutyric acid in nonphotoreceptor neurons, whereas photoreceptors were labeled predominantly with 3H-glutamate. Most of the photoreceptors were labeled with fluorescent peanut lectin and with a sheep polyclonal antibody against bovine rhodopsin. Subsets of photoreceptors, on the other hand, were immunoreactive with cone- or rod-specific monoclonal antibodies COS-1, OS-2, 50-1B11, or Rho-4D2. Approximately 50% to 65% of the photoreceptors positive with these monoclonal antibodies showed a remarkable polarization of immunoreactive materials, which accumulated predominantly, or even exclusively, in an outer-segment-like apical process. When viewed on the transmission electron microscope, these outer-segment-like processes appeared as distal expansions of the photoreceptor cilium and contained disc-like membranous profiles. Outer-segment-like processes also could be detected using the electron microscope and by immunocytochemical analysis of cultures of ED 8 retinal cells. CONCLUSIONS: After undergoing morphologic dedifferentiation as a result of tissue dissociation, isolated retinal photoreceptors, grown in the absence of contact-mediated cell interactions and of pigment epithelial and glial cells, can regenerate and maintain a highly polarized pattern of structural and molecular organization, including the formation of outer-segment-like processes. The cultures provide an experimental system for the investigation of cellular and molecular mechanisms regulating further development and maturation of these photoreceptor structures.

Animals↗
PubMed1995

Hodgkin's disease as an indicator of AIDS.

Hodgkin's disease (HD) is not currently included within the Centers for Disease Control (CDC) classification system for AIDS. Upon HD diagnosis, HIV(human immunosuppressive virus)-positive patients are generally found within Stages III or IV of the Ann Arbor HD classification system, already exacerbating the problem of treatment. In contrast, HIV-negative patients diagnosed with HD are generally found within Stages I or II. Epidemiology and the presence of secondary lymphomas, opportunistic infections, or aggressive pathologies, accompanied by low survival rate and timing of HD diagnosis suggest that HD should be included among conditions indicating AIDS manifestation.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Chromokinesin: a DNA-binding, kinesin-like nuclear protein.

Microtubule-associated mechanoenzymes have been proposed to play a fundamental role in chromosome movement. We have cloned and characterized the cDNA for a novel protein, named Chromokinesin, that fulfills several of the criteria expected of a mitotic motor. Chromokinesin contains both a kinesin motor-like domain and an unusual basic-leucine zipper DNA-binding domain. Its mRNA is readily detectable in proliferating cells, but not in postmitotic cells. Immunocytochemical analysis with antibodies directed against the nonconserved COOH-terminal region of Chromokinesin indicates that the protein is localized in the nucleus, and primarily associated with chromosome arms in mitotic cells. These data suggest that Chromokinesin is likely to function as a microtubule-based mitotic motor with DNA as its cargo.

Amino Acid Sequence↗
PubMed1995

Biliary cystadenoma of cats.

Published surveys of feline neoplasia have not specifically included biliary cystadenoma, and there is only one case report in the literature. This report is a compilation of 13 feline cases and provides a description of clinical, pathologic, immunohistochemical, and ultrastructural aspects of biliary cystadenoma as well as a discussion of comparative pathology of biliary cystadenoma in human beings and speculative histogenesis.

Adenoma, Bile Duct↗
PubMed1995

Specific targeting of adriamycin conjugates with monoclonal antibodies to hepatoma associated antigens to intrahepatic tumors in athymic mice.

Doxorubicin (adriamycin), once considered the treatment of choice for hepatocellular carcinoma (HCC), is known to cause cardiotoxicity and myelotoxicity. To reduce the systemic toxicity of adriamycin by direct delivery of the drug to the tumor site, we established a panel of monoclonal antibodies (MAbs) to hepatoma associated antigens that were conjugated to adriamycin by a dextran bridge. Initially, the efficacy of these conjugates in suppressing tumor growth was assessed using a model of subcutaneous HCC tumors injected in athymic mice. In the second stage of the study, we tested these conjugates in an experimental model in which human HCC was transplanted intrahepatically by intrasplenic injection, thus providing the tumor cells with growth factors and an adequate cellular matrix, similar to the natural microenvironment of HCC. Anti-tumoral therapy resulted in lower serum alpha-fetoprotein (AFP) levels in two of three experimental groups treated with different specific conjugates as compared with control mice treated with the individual components. Efficacy of targeting was enhanced using the intrahepatic model system for propagation of HCC and was demonstrated by fluorescence of adriamycin and MAb in tumor tissue and absence of this fluorescence in healthy liver tissue surrounding the tumor. Reduction of systemic toxicity was shown by the absence of adriamycin fluorescence in myocardial tissue in conjugate-treated mice, whereas in all other treatment groups, including mice treated with a mixture of adriamycin and specific MAb, there was strong myocardial fluorescence of adriamycin.

Animals↗
PubMed1995

Successful immunization of autologous bone marrow transplantation recipients against hepatitis B virus by active vaccination.

Patients undergoing autologous bone marrow transplantation (BMT) are severely immunosuppressed. These patients are exposed to various infections agents due to delayed and efficient reconstitution of their immune system. Forty-eight patients with hemato-oncological malignancies were immunized against hepatitis B virus (HBV) following autologous BMT. Twenty one were vaccinated more than 10 days before BMT, 17 on days 1-9 before and 10 day after BMT. Thirty three patients (68.7%) seroconverted within 40 days after autologous BMT after receiving one dose of the vaccine before autologous BMT with a relatively low level of anti-HBs, whereas in 11 no anti-HBV antibodies could be detected. Nineteen patients remained seropositive but in 11 the seroconversion was only transient no correlation was found between permanent or transient seroconversion and basic disease, conditioning regimens, post-transplant therapy, immunotherapy and day of vaccination in relation to autologous and day of vaccination in relation to autologous BMT. Active HBV immunization of patients with malignancy undergoing autologous BMT is feasible and levels of antibodies, although low, are above the conventional protective titers. Therefore active immunization of some patients may reduce hepatitis-related complications in the setting of autologous BMT.

Adolescent↗