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Biomedical subjects

R Adler

Publications and source records attributed to R Adler.

At least 73 records · Page 4Linked to original sources
PubMed1995

Apoptotic photoreceptor degeneration in experimental retinal detachment.

PURPOSE: To investigate the possibility that cell death in retinal detachment may occur by reactivation of apoptotic programmed cell death mechanisms. METHODS: Unilateral retinal detachments were created in adult cats using 0.25% sodium hyaluronate; detached and control retinas were studied at different intervals. Internucleosomal DNA fragmentation (one of the landmarks of apoptosis) was investigated in tissue sections with the TUNEL technique, which uses terminal transferase to label with biotinylated nucleotides the 3' ends of DNA fragments. Sections also were labeled with propidium iodide, which intensely stains pyknotic nuclei. In addition, one time point was selected for analysis with electron microscopy. RESULTS: TUNEL-positive (T+) and propidium iodide-positive (PI+) cells almost never were observed in retinas from control eyes, but they were abundant at defined time points after retinal detachment, appearing almost exclusively in the photoreceptor layer. Their frequency was particularly high 1 to 3 days after detachment but declined rapidly over the next several weeks. T+ cells were still present 28 days after retinal detachment. Electron microscopy also revealed evidence of apoptotic cells after retinal detachment. CONCLUSIONS: Results are consistent with the hypothesis that photoreceptor degeneration after retinal detachment occurs through apoptosis, usually associated with intrinsic, programmed cell death mechanisms. The detection of a rapid wave of photoreceptor degeneration seems to suggest that early therapeutic interventions might be recommended; agents capable of interfering with the apoptotic mechanism could have a role in the prevention of cell losses that represent a critical complication of retinal detachment.

Animals↗
PubMed1994

A developmentally regulated basic-leucine zipper-like gene and its expression in embryonic retina and lens.

Transcriptional regulators play important roles in the control of key developmental events. We have identified sw3-3, a likely candidate for such a function, in tissues of the eye and other neural organs. It encodes a basic-leucine zipper-like protein, in which two leucine zipper motifs flank a basic domain. The latter contains helix-disturbing amino acids such as glycine and proline, at positions occupied by conserved asparagine and alanine residues (respectively) in "conventional" basic-leucine zipper proteins. sw3-3 is widely expressed at early embryonic stages in the lens, retina, and other neural tissues and is down-regulated thereafter with a spatial and temporal pattern that correlates with the cessation of mitotic activity and the onset of cell migration and differentiation.

Amino Acid Sequence↗
PubMed1994

Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited human diseases in which photoreceptor degeneration leads to visual loss and eventually to blindness. Although mutations in the rhodopsin, peripherin, and cGMP phosphodiesterase genes have been identified in some forms of RP, it remains to be determined whether these mutations lead to photoreceptor cell death through necrotic or apoptotic mechanisms. In this paper, we report a test of the hypothesis that photoreceptor cell death occurs by an apoptotic mechanism in three mouse models of RP: retinal degeneration slow (rds) caused by a peripherin mutation, retinal degeneration (rd) caused by a defect in cGMP phosphodiesterase, and transgenic mice carrying a rhodopsin Q344ter mutation responsible for autosomal dominant RP. Two complementary techniques were used to detect apoptosis-specific internucleosomal DNA fragmentation: agarose gel electrophoresis and in situ labeling of apoptotic cells by terminal dUTP nick end labeling. Both methods showed extensive apoptosis of photoreceptors in all three mouse models of retinal degeneration. We also show that apoptotic death occurs in the retina during normal development, suggesting that different mechanisms can cause photoreceptor death by activating an intrinsic death program in these cells. These findings raise the possibility that retinal degenerations may be slowed by interfering with the apoptotic mechanism itself.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1994

Cell-type- and developmental-stage-specific metabolism and storage of retinoids by embryonic chick retinal cells in culture.

Biological functions of retinoids in the vertebrate retina include the role of 11-cis retinaldehyde as visual pigment chromophore, and possible effects of retinoic acid in histogenesis and cell survival. Qualitative and quantitative regulation of retinoid availability for these complex processes could involve several cell types, including retinal pigment epithelium, Müller glia and retinal photoreceptors and non-photoreceptor neurons; their relative contributions, however, have not been fully elucidated. Using purified cultures, we have carried out a study of cell-type-specific metabolism and storage of retinoids in chick embryo retinal photoreceptors and other neuronal cells, as compared to those of retinal glia. Retinal glia were found to synthesize both retinoic acid and retinyl esters, and to hydrolyse the latter; they also displayed retinol dehydrogenase activities. Cultured neurons and photoreceptors also synthesized and hydrolysed retinyl esters; their capacity for retinaldehyde synthesis from a retinol or retinyl ester substrate suggested the presence of retinol dehydrogenase activity. Retinoic acid was not synthesized in differentiated neuronal cultures, although some synthesis was detectable at early culture stages when the cells were still morphologically undifferentiated. These findings indicate that cell-type-specific metabolic activities are expressed during retinal cell differentiation in vitro, and that embryonic retinal photoreceptors and nonphotoreceptor neurons are active participants in the metabolism and storage of retinoids.

Animals↗
PubMed1994

Improved immunogenicity in mice of a mammalian cell-derived recombinant hepatitis B vaccine containing pre-S1 and pre-S2 antigens as compared with conventional yeast-derived vaccines.

The widely used hepatitis B virus (HBV) vaccines consist of the small hepatitis B surface (SHBs) protein produced in transfected yeast cells. The frequency of non-responders, especially among immunocompromised patients, has increased the demand for a more immunogenic vaccine. We evaluated the immunogenicity of recombinant HBs 20 nm particles secreted by transfected Chinese hamster ovary (CHO) cells, Bio-Hep-B (BioTechnology General Ltd, Israel), and compared it with yeast-derived vaccines. The CHO-derived vaccine contains the small hepatitis B surface antigen (SHBs protein) as the major component, as well as the middle HBs (MHBs, pre-S2) and the large HBs (LHBs, pre-S1) antigens. Nine groups of ten female Balb/c mice, 4-6 weeks old, were injected once intraperitoneally (i.p.) with 0.09, 0.27 or 0.81 micrograms of each of three vaccines: Bio-Hep-B or two conventional yeast-derived recombinant vaccines, Engerix-B (SmithKline Beecham, Belgium) and H-B-Vax II (Merck, Sharp & Dohme, USA) containing only non-glycosylated SHBs antigen. After 30 days, 40% of the mice injected with 0.09 microgram Bio-Hep-B had seroconverted, but none of the mice receiving the same dose of the other vaccines. The immunogenic dose in 50% of the mice at day 14 after injection was 0.13 microgram for Bio-Hep-B, but over 0.81 microgram for the other two vaccines. Mice of the strain B10/M (which are unresponsive to SHBs and MHBs antigens at the T-cell level) developed 100-fold higher anti-HBs titres after immunization with 1 microgram of Bio-Hep-B i.p., as compared with mice receiving the same amount of yeast-derived HBsAg vaccines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Secondary prevention of childhood firesetting.

OBJECTIVE: The Juvenile Fire Awareness and Intervention Program was established to develop and evaluate an intervention to be offered by fire fighters for children who set fires. METHOD: One hundred thirty-eight children, aged 5 to 16 years, with a history of firesetting participated in a randomized, controlled trial. The intervention involved education about fire safety and a behavior modification program designed to extinguish the desire to set fires through satiation. The frequency and severity of firesetting were recorded for 12 months after the intervention to measure outcome. RESULTS: There was a significant decrease in the frequency and severity of firesetting across all groups, with no additional improvement resulting from participation in the fire fighters' intervention. CONCLUSIONS: There is no evidence to suggest that the multicomponent program offered by trained fire fighters is effective in reducing firesetting. The marked reduction in firesetting across all groups suggests that fire safety education by the fire fighters is the most appropriate approach to this serious community problem.

Adolescent↗
PubMed1994

Development of antibodies to hepatitis B virus surface antigen in bone marrow transplant recipient following treatment with peripheral blood lymphocytes from immunized donors.

Bone marrow transplantation (BMT) recipients are immunosuppressed and are at risk for contracting severe infections. Recently, adoptive transfer of immunity against hepatitis B virus (HBV) was documented in BMT recipients receiving bone marrow from 'naturally' HBV-infected individuals who recovered spontaneously, or those transplanted with bone marrow cells obtained from actively immunized donors. Furthermore, reconstitution of the immune system in a BMT recipient who was a hepatitis surface antigen (HBsAg)+/HBV DNA+ carrier with HBV immune bone marrow cells led to clearance of the replicating virus, presumably through adoptive cell-mediated immunotherapy. We report three cases of induction of immunity to HBV by selective adoptive transfer by i.v. injection of peripheral blood lymphocytes (PBL) obtained from BMT donors who were actively immunized against HBV after harvesting of bone marrow. All three BMT recipients developed anti-HBs antibodies. In one BMT case in whom antibodies to HBsAg developed following adoptive transfer of immune PBL, a mild booster effect was documented in the BMT recipient upon immunization with a recombinant hepatitis B vaccine. The two remaining patients lost their antibodies to HBsAg in association with relapse of leukaemia. This immune manipulation may open the door to evaluation of adoptive transfer of immunity to HBV through selective transplantation of HBV immune lymphocytes in selected patients such as those with persistent HBV infection, as well as liver transplant recipients who require protection of the graft against HBV re-infection.

Adolescent↗
PubMed1994

Bleeding on probing. A parameter for monitoring periodontal conditions in clinical practice.

The present study is a follow-up report on the use of bleeding on probing (BOP) as a clinical indicator for disease progression or periodontal stability, respectively. Following active periodontal therapy, 39 patients were incorporated in a program of supportive periodontal therapy for a period of 53 months with recall intervals varying between 2-8 months. The patients received supportive therapy 7 to 14 x. At the beginning of each maintenance visit, the tissues were evaluated using BOP. Reinstrumentation was only performed at sites which bled on probing. However, supragingival plaque and calculus were always removed. Probing depth and probing attachment levels were determined after active treatment and at the conclusion of the study. Progression of periodontal disease was defined by a measured loss of probing attachment of 2 mm or more. During the observation period, 4.2% of all the sites lost attachment. Approximately 50% of these losses were due to periodontal disease progression, while the other half was the result of attachment loss in conjunction with recession of the gingiva. 2/3 of all the sites which lost attachment were found in a group of patients which presented a mean BOP > or = 30%. In a group of patients with a mean BOP of < or = 20%, only 1/5 of the loser sites were found. This clearly indicated, that patients with a mean BOP of < or = 20% have a significantly lower risk for further loss of probing attachment at single sites.

Dental Prophylaxis↗
PubMed1994

Photomechanical movements of cultured embryonic photoreceptors: regulation by exogenous neuromodulators and by a regulable source of endogenous dopamine.

In the retina of nonmammalian vertebrates, light regulates photoreceptor morphology by causing rod photoreceptor elongation and cone photoreceptor contraction. The opposite photomechanical movements occur in the dark, and proceed with a circadian rhythm in many species in vivo. Using dissociated cultures of embryonic chick retina cells, we have recently demonstrated that photoreceptor cells that differentiate in vitro acquire the capacity of responding to light/dark cycles with photomechanical movements (Stenkamp and Adler, 1993). Here we report that the putative neuromodulators melatonin and dopamine can mimic the effects of darkness and light, respectively, on in vitro photomechanical movement. Pharmacological studies showed that dopamine appears to function by means of a D2-type receptor negatively coupled to adenylate cyclase. The effects of light on the cultured photoreceptors were inhibited by dopamine D2 receptor antagonists, and were attenuated by the dopaminergic neurotoxin 6-hydroxydopamine and by the dopamine synthesis inhibitor alpha-methyl-p-tyrosine. The possible existence of an endogenous source of dopamine in the cultures was also suggested by the presence of tyrosine hydroxylase-like immunoreactivity, and of an Na(+)-dependent mechanism for the accumulation of 3H-dopamine, which was predominantly associated with nonphotoreceptor cells. Additionally, 3H-dopamine release occurred in vitro through a Ca(2+)-dependent mechanism, as well as through reverse function of a nomifensine-sensitive dopamine transporter. Both of these putative release mechanisms appeared to be regulated by light and by melatonin, suggesting a mechanism whereby the putative dopaminergic cells may interact with other cells present in the cultures. These studies suggest that complex paracrine neuromodulatory mechanisms can differentiate in low-density embryonic cell culture, that dopaminergic activities exist in vitro, and that they are important for mediating photomechanical movements.

Animals↗
PubMed1993

Photoreceptor differentiation of isolated retinal precursor cells includes the capacity for photomechanical responses.

Isolated retinal precursor cells, grown without pigment epithelial or glial cells and in the absence of intercellular contacts, develop a complex set of photoreceptor-specific properties, including polarized structural and molecular organization and opsin immunoreactivity. We report here that these isolated embryonic photoreceptors are also capable of responding to light. Sequential photography showed that 50% of the photoreceptors grown in a light cycle elongate when exposed to light and contract in response to darkness. A smaller population (20%) showed the opposite response. Responses of individual cells could be observed during several sequential light cycles and resemble photomechanical movements in vivo [Ali, M. A. (1971) Vision Res. 11, 1225-1288]. The differentiation program expressed by isolated precursor cells, therefore, includes the capacity for highly complex functional activities that require light sensitivity. These observations raise challenging questions regarding the nature of the chromophore and pigments that mediate light-regulated behaviors of cultured photoreceptors.

Animals↗
PubMed1993

Ablation of persistent hepatitis B by bone marrow transplantation from a hepatitis B-immune donor.

Chronic hepatitis B virus (HBV) infection is still a major cause of liver disease for which no definite therapy is available. We describe here a hepatitis B surface antigen (HBsAg) carrier patient with active viral replication (HBV DNA positive) who was treated for leukemia by bone marrow transplantation (BMT) from an HBV immune donor. Following BMT from the antibody to hepatitis B core antigen (anti-HBc) positive/anti-HBs positive bone marrow donor, immune reconstitution of the recipient's bone marrow resulted in clearance of the circulating HBsAg, as well as HBV DNA. The patient acquired immunity against HBV, which lasted for more than 8 months posttransplantation. Therefore, this report provides evidence that adoptive transfer of specific immunity against HBV through allogeneic BMT may lead to clearance of persistent HBV infection. Furthermore, the data support the hypothesis that the HBsAg carrier state is most probably the result of an inefficient immune response against HBV, implying that clearance of HBV may be facilitated by adoptive cellular immunotherapy.

Bone Marrow Transplantation↗
PubMed1993

Single and booster dose responses to an inactivated hepatitis A virus vaccine: comparison with immune serum globulin prophylaxis.

Pre- and postexposure prophylaxis against hepatitis A virus (HAV) infection with immune serum globulin (Ig) is only effective for 4-6 months. We compared the safety, tolerability and immunogenicity of a single i.m. injection of Ig with a single and booster dose of an inactivated hepatitis A virus vaccine (iHAV) in adults. Healthy volunteers (18-50 years) received a single Ig i.m. injection (n = 30), or iHAV i.m. (n = 15) at 0 and 24 weeks, or placebo (n = 4) at the same intervals. Anti-HAV seroconversion was measured by radioimmunoassay (RIA) and neutralizing antibodies by an antigen reduction assay. After Ig injection (0.06 ml/kg), anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12 and 0% by week 20. In contrast, after a single 25 ng dose, RIA seropositivity in iHAV vaccinees was 80% by week 2, reaching 100% by week 5 and persisted up to week 24, at which time anti-HAV geometric mean titres (GMT) were two fold higher than those seen at week 1 after Ig. Postbooster anti-HAV titres in iHAV recipients rose within 4 weeks to 73-fold greater than the peak GMT seen one week after Ig, and 400-fold higher than GMT at 12 weeks after Ig. Neutralizing antibody titres after iHAV followed a similar pattern, as observed for anti-HAV. iHAV was well tolerated; placebo and vaccine tolerability were indistinguishable, with no serious adverse experiences observed. In conclusion, active vaccination with a single iHAV dose may eventually replace Ig for pre-exposure prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Ciliary neurotrophic factor as an injury factor.

This article reviews recent evidence suggesting that endogenous ciliary neurotrophic factor may be involved in neural responses to injury, and discusses the possibility that ciliary neurotrophic factor could have therapeutic applications in a clinical setting. The functional relevance of ciliary neurotrophic factor in non-injury situations is also evaluated, with emphasis on its possible roles in embryonic development.

Animals↗
PubMed1993

A finger-stick assay for determination of immunity to hepatitis A: a preliminary report.

A simple and reproducible method for determining immunity to hepatitis A has been developed, using whole blood obtained by finger-stick and fixed on small discs. This method permits screening of large populations of candidates prior to active or passive immunization, avoiding the discomfort and difficulty of venipuncture, especially in children. The technique involves a finger-stick with a blood lancet, collection of 20 microliter whole blood on a paper disc which is then dried at room temperature. Perforated discs are incubated with phosphate buffered saline and the eluate is then tested for anti-HAV using the HAVAB assay. Results of anti-HAV assays from finger-stick samples obtained from adults and from children, showed 100% conformance with the homologous venous serum samples obtained at the same time. The lower threshold for detection of anti-HAV by this method is currently below 100 mIU/ml, as compared to 20 mIU/ml by the modified HAVAB method. In conclusion, we have developed a simple and reliable method for determination of immunity to HAV using whole blood obtained by finger-stick and fixed on paper discs. Samples can be collected under field trial conditions, without immediate need for laboratory facilities for separation and storage of serum samples. This sampling method, which is mainly intended for qualitative determination of anti-HAV in HAV immune subjects, especially under field trial conditions, is rapid, economical, efficient and acceptable to populations that are generally apprehensive of conventional venipuncture specimen collection methods.

Blood Specimen Collection↗
PubMed1993

Safety, tolerability, and immunogenicity of an inactivated hepatitis A vaccine: effects of single and booster injections, and comparison to administration of immune globulin.

Hepatitis A virus (HAV) infection in adults is often symptomatic and disabling. The present article summarizes our experience with phase 2 studies of an inactivated hepatitis A virus vaccine. Pre- and post-exposure prophylaxis with immune globulin (IG) is only effective for 4-6 months. We compared the safety, tolerability, and immunogenicity of a single i.m. injection of IG with single and booster doses of an inactivated hepatitis A virus vaccine (iHAV) in adults. A total of 75 healthy volunteers (aged 18-50 years) were evaluated in two separate studies. The first included 15 volunteers who received 25 units iHAV i.m. at 0 and 24 weeks. The second, a randomly controlled study, consisted of three groups receiving 25 units iHAV i.m. at 0, 1, and 6 months, or at 0, 2, and 6 months, or 0.06 ml/kg IG i.m. given once. Anti-HAV seroconversion was measured by radioimmunoassay (RIA). After IG injection, anti-HAV seroconversion occurred in 100% of recipients at week 1, declining to 10% at week 12, and 0% by week 20. In contrast, after a single 25-unit dose, RIA seropositivity in iHAV vaccines was 73% by week 2, reaching 100% by week 5, and persisted in all up to week 24, at which time anti-HAV geometric mean titers (GMT) were 2-fold higher than those seen at week 1 after IG. Administration of a booster dose given 1 or 2 months after primary immunization did not significantly improve the quantitative anti-HAV response at 6 months as compared to the effect of the primary dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗