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Biomedical subjects

D Horowitz

Publications and source records attributed to D Horowitz.

11 recordsLinked to original sources
PubMed2001

Rapid mobilization of murine hematopoietic stem cells with enhanced engraftment properties and evaluation of hematopoietic progenitor cell mobilization in rhesus monkeys by a single injection of SB-251353, a specific truncated form of the human CXC chemokine GRObeta.

SB-251353 is an N-terminal truncated form of the human CXC chemokine GRObeta. Recombinant SB-251353 was profiled in murine and rhesus monkey peripheral blood stem cell mobilization and transplantation models. SB-251353 rapidly and transiently mobilized hematopoietic stem cells and neutrophils into the peripheral blood after a single subcutaneous injection. Transplantation of equivalent numbers of hematopoietic stem cells mobilized by SB-251353 into lethally irradiated mice resulted in faster neutrophil and platelet recovery than stem cells mobilized by granulocyte colony-stimulating factor (G-CSF). A single injection of SB-251353 in combination with 4 days of G-CSF administration resulted in augmented stem and progenitor cell mobilization 5-fold greater than G-CSF alone. Augmented stem cell mobilization could also be demonstrated in mice when a single injection of SB-251353 was administered with only one-day treatment with G-CSF. In addition, SB-251353, when used as a single agent or in combination with G-CSF, mobilized long-term repopulating stem cells capable of hematopoietic reconstitution of lethally irradiated mice. In rhesus monkeys, a single injection of SB-251353 induced rapid increases in peripheral blood hematopoietic progenitor cells at a 50-fold lower dose than in mice, which indicates a shift in potency. These studies provide evidence that the use of SB-251353 alone or in combination with G-CSF mobilizes hematopoietic stem cells with long-term repopulating ability. In addition, this treatment may (1) reduce the number of apheresis sessions and/or amount of G-CSF required to collect adequate numbers of hematopoietic stem cells for successful peripheral blood cell transplantation and (2) improve hematopoietic recovery after transplantation.

Animals↗
PubMed2000

Colorimetric determination of inhibition of hematopoietic progenitor cells in soft agar.

In vitro colony forming unit (CFU) assays have been used to measure the effects of compounds that regulate the growth of hematopoietic progenitor cells. These assays are time consuming and subjective and are therefore not amenable to high throughput of large numbers of compounds. Here we have shown that the traditional murine bone marrow CFU assay can be modified into a robust non-subjective colorimetric assay format. 3-[4,5-Dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) was added after colony formation in an agar based 96-well plate culture system. Optical density correlated with increasing cell input concentrations in the presence of growth factor. The linearity of this response was equivalent to the standard CFU assay. Several hematopoietic inhibitors were tested in both assays. Effects on colony number and size were compared to optical density. Compounds that reduced colony numbers with little effect on colony size had identical IC(50) values in both the colorimetric assay and CFU assay. The IC(50) values of compounds that also decreased colony size did not correlate in the two assays. These results demonstrate the utility of the colorimetric assay to rapidly screen for compounds that specifically inhibit hematopoietic progenitor cell colony formation in vitro.

Animals↗
PubMed2000

Assessing the value of structured protocols for forensic interviews of alleged child abuse victims.

OBJECTIVE: To evaluate the effectiveness of a structured interview protocol (NICHD Investigative Interview Protocol) operationalizing universally recommended guidelines for forensic interviews. METHOD: The NICHD Investigative Protocol was designed to maximize the amount of information obtained using recall memory probes, which are likely to elicit more accurate information than recognition memory probes. Forensic investigators were trained to use the NICHD protocol while conducting feedback-monitored simulation interviews. The utility of the protocol was then evaluated by comparing 55 protocol interviews with 50 prior interviews by the same investigators, matched with respect to characteristics likely to affect the richness of the children's accounts. The comparison was based on an analysis of the investigators' utterance types, distribution, and timing, as well as quantitative and qualitative characteristics of the information produced. RESULTS: As predicted, protocol interviews contained more open-ended prompts overall as well as before the first option-posing utterance than non-protocol interviews did. More details were obtained using open-ended invitations and fewer were obtained using focused questions in protocol interviews than in non-protocol interviews, although the total number of details elicited did not differ significantly. In both conditions, older children provided more details than younger children did. CONCLUSION: The findings confirmed that implementation of professionally recommended practices affected the behavior of interviewers in both the pre-substantive and substantive phases of their interviews and enhanced the quality (i.e., likely accuracy) of information elicited from alleged victims.

Adolescent↗
PubMed2000

Accuracy of investigators' verbatim notes of their forensic interviews with alleged child abuse victims.

Verbatim contemporaneous accounts of 20 investigative interviews were compared with audiotaped recordings thereof. More than half (57%) of the interviewers' utterances along with 25% of the incident-relevant details provided by the children were not reported in the "verbatim" notes. The structure of the interviews was also represented inaccurately in these accounts. Fewer than half (44%) of the details provided by the children were attributed to the correct eliciting utterance type. Investigators systematically misattributed details to more open rather than more focused prompts. These results underscore the superiority of electronic recording when the content and structure of investigative interviews must be preserved.

Adolescent↗
PubMed1994

Identification of overlapping class I and class II H-2d-restricted T cell determinants of influenza virus N1 neuraminidase that require infectious virus for presentation.

The requirement for endogenous viral protein synthesis in helper and cytotoxic T cell (CTL) recognition of influenza virus was studied at the level of individual epitopes. The viral envelope glycoprotein neuraminidase (NA) contains class I and class II major histocompatibility complex (MHC)-restricted T cell determinants that are presented by virus-infected antigen-presenting cells (APC). We had previously shown that recognition of NA by class II I-Ed-restricted T cells required either active viral infection of APC or introduction of uv-inactivated virus to the cytosol, similar to the well-established requirements for class I-restricted responses. Detailed mapping of T cell epitopes was undertaken using vaccinia virus vectors encoding truncated segments of the influenza NA molecule and by synthetic peptides. Class I MHC-restricted CTL were found to recognize two regions of NA: residues 69-89 in the context of Dd and 191-201 presented by Kd. Analyses of T cell proliferation and T hybridoma clones revealed that class II-restricted responses recognized the same two regions as the CTL, presented by I-Ed and I-Ad, respectively. Interestingly, both class I and class II MHC-restricted T cells showed similar requirements for endogenously synthesized antigen, responding poorly or not at all to endocytosed uv-inactivated virus. This extends previous observations that specific epitopes can be preferentially presented by class II molecules from endogenously synthesized antigens and shows that the same antigenic determinants can have access to both class I and class II antigen presentation pathways.

Amino Acid Sequence↗
PubMed1993

Rare case of double aortic arch with hypoplastic right dorsal segment and associated tetralogy of Fallot: MR findings.

We report a rare case of double aortic arch with a hypoplastic right dorsal arch segment, which was also associated with tetralogy of Fallot. Accurate characterization of the hypoplastic right arch segment by MRI preoperatively determined the optimal surgical approach to releasing the symptomatic vascular ring. MRI was also useful in assessing and monitoring associated tracheomalacia.

Aorta, Thoracic↗
PubMed1992

Influenza virus infection elicits class II major histocompatibility complex-restricted T cells specific for an epitope identified in the NS1 non-structural protein.

A T cell epitope of the influenza virus NS1 molecule was identified and shown to be a determinant used in class II major histocompatibility complex-restricted T cell responses to infectious virus. An I-Ed-restricted BALB/c mouse T hybridoma clone recognizing influenza virus A/Puerto Rico/8/34 (PR8; subtype H1N1) but not A/Udorn/72 (subtype H3N2) secreted lymphokines in response to purified recombinant NS1 or fusion proteins containing amino acids 1 to 81 or 1 to 42 of NS1. As expected for recognition of a non-virion protein, the clone failed to respond to u.v.-inactivated virus. The antigenic determinant was localized by synthetic peptides to amino acids 13 to 32 of NS1, explaining the lack of recognition of A/Udorn/72 virus which has an alanine to valine substitution at position 23 within the determinant. A single intranasal dose of infectious PR8 virus was found to elicit T cells that responded to peptide NS1 13-32, suggesting that this determinant is a significant target of T cells in normal infections. To stimulate helper T cell responses similar to those achieved with infectious virus, influenza virus vaccines may therefore have to include NS1 in addition to virion components.

Amino Acid Sequence↗
PubMed1991

Immunogenic peptides of influenza virus subtype N1 neuraminidase identify a T-cell determinant used in class II major histocompatibility complex-restricted responses to infectious virus.

Six nonoverlapping peptides of the neuraminidase (NA) glycoprotein of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8 virus) were found to be immunogenic for proliferating T cells when injected into BALB/c mice in Freund adjuvant. T cells elicited by peptide immunization could recognize PR8 virus in vitro. However, only one of these peptides, corresponding to residues 79 to 93 of NA (NA 79-93), was able to restimulate T cells of mice immunized with infectious virus. T cells that recognized this peptide were uniformly I-Ed restricted, yet infectious influenza virus was required for responses. NA 79-93-specific T-hybridoma clones raised by immunization either with whole virus or with the synthetic peptide alone each responded to replicative virus and not to UV-inactivated virions. These data suggest that the NA 79-93 T-cell determinant which is commonly presented during an encounter with influenza virus in vivo is processed preferentially from NA synthesized within antigen-presenting cells.

Amino Acid Sequence↗
PubMed1985

Iron detoxification by haemoperfusion through deferoxamine-conjugated agarose-polyacrolein microsphere beads.

The natural iron chelator deferoxamine was bonded to agarose-polyacrolein microsphere beads (APAMB). This novel deferoxamine-conjugated APAMB (DCA), when used as the sorbent in a plasma/haemoperfusion system, showed specific and rapid removal of iron from plasma and blood in vitro; in vivo experiments also showed specific iron removal. The advantages of this sorbent are minimal damage to biocompounds during haemoperfusion, high capacity and specificity to iron, and the possibility of reuse.

Acrolein↗
PubMedDate not supplied

Deficiency of plasma protein S, protein C, or antithrombin III and arterial thrombosis.

Protein C and protein S are vitamin K-dependent coagulation factors that together act as an anticoagulant, and antithrombin III is a plasma protein that inhibits several activated factors in the coagulation cascade. Although deficiencies of any of these three proteins have been associated with deficiencies of these factors. We report one patient with a protein S deficiency, another with a protein C deficiency, and a third with an antithrombin III deficiency, each of whom who had extensive arterial thrombosis. We suggest that deficiencies of these proteins may constitute risk factors for arterial thrombosis.

Adult↗