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P Rubinstein

Publications and source records attributed to P Rubinstein.

At least 37 records · Page 2Linked to original sources
PubMed1998

Unrelated mismatched cord blood transplantation in patients with hematological malignancies: a single institution experience.

We report on six cases of unrelated UCB transplant in adult patients with hematological malignancies: three chronic myelocytic leukemias and three acute leukemias. Their median age and body weight were respectively: 28 years (range 15.5-40) and 55.5 kg (range 46-90). The cord blood units were from the New York Blood Center. The median number of nuclear cells provided, evaluated before thawing, was 2.1 x 10(7)/kg (range 1 x 10(7)/kg-4.7 x 10(7)/kg). The degree of HLA disparity was 1/6: two patients, 2/6: three patients, 3/6: one patient. The patients received a pretransplant regimen including total body irradiation. They were given graft-versus-host disease prophylaxis which consisted of cyclosporin A and corticosteroids. They were all given a combination of G-CSF and erythropoietin. The median time of white blood cell and platelet reconstitution were respectively 24 days (range 12-43) and 60 days (range 23-90). All the patients had a full chimerism. A grade I acute GVHD was observed in four patients and two patients do not have any GVHD. No chronic GVHD has been observed yet. Three patients died from toxicity. Three patients are alive and well in complete remission at 2 years, 1 year and 11 months post-graft.

Adolescent↗
PubMed1998

[Repeat surgery for thyroid nodules (excluding cancer and hyperthyroidism)].

Second procedures for recurrent thyroid disease are known to carry a high risk of iatrogenic damage, particularly to the inferior laryngeal nerves and parathyroid glands. This risk has been clearly evaluated for the primary procedure, but is less clearly for second procedures. A series of 117 patients with solitary or multiple cold thyroid nodules were evaluated (excluding those patients re-operated for recurrent thyroid carcinoma or goitre associated with hyperthyroidism) to determine the operative risks. The level of transient and permanent recurrent laryngeal nerve palsy was 2.56% and 1.7% respectively. The level of transient and permanent hypocalcaemia was 12.9% and 4.62% respectively. The frequency of re-operation for recurrent disease involving the pyramidal lobe following total thyroidectomy (6 cases) highlights the importance of removing it during the primary procedure. The number of cases of cancer discovered at re-operation was 4.3% (5 cases out of 117).

Adult↗
PubMed1997

A murine model for human cord blood transplantation: near-term fetal and neonatal peripheral blood cells can achieve long-term bone marrow engraftment in sublethally irradiated adult recipients.

The purposes of the research reported here were first to explore a murine model for human placental and umbilical cord blood transplantation and second to evaluate the engraftment ability of ex vivo cultured hematopoietic cells. Murine near-term fetal and neonatal peripheral blood (FNPB) cells, genetically marked with the human multiple drug resistance transgene (MDR1) were used for syngeneic transplants into sublethally irradiated adult mice. Donor cells were transplanted either fresh and untreated, or after ex vivo culture in the presence of the hematopoietic growth factors recombinant murine stem cell factor, recombinant human interleukin-3 (rHu IL-3), and rHu IL-6, in a liquid culture system. To evaluate, count, and characterize FNPB progenitor cell-derived colonies, neonatal mouse mononuclear cells were cultured directly in methylcellulose with growth factors. To assess their ex vivo expansion ability, FNPB mononuclear cells were first cultured in liquid medium for 3 to 8 days and then transferred to semisolid assay plates. Evaluation of the cell counts after liquid culture showed a 1.4- to 11.6-fold increase, and the numbers of colonies observed in methylcellulose were similar to those produced by fresh FNPB cells. Donor-type engraftment was demonstrated by polymerase chain reaction (PCR) amplification of the human MDR1 transgene in the peripheral blood of all surviving animals (5 of 7 recipients of the fresh, and 3 of 8 recipients of the ex vivo-cultured cells) 2 to 4 months after transplantation. The proportion of donor leukocytes in the peripheral blood of the recipients (chimerism) was evaluated using fluorescence in situ hybridization (FISH) analysis 4 to 6 months after transplantation and ranged from 2% to 26%. In addition, bone marrow cultures were obtained from two recipient animals: one had received fresh-untreated cells and was evaluated 8 months after transplant, the other had received ex vivo cultured cells and was tested 14 months after grafting. The derived hematopoietic colonies were tested by PCR and the transgene was detected, conclusively proving long-term engraftment of donor cells. These results indicate that FNPB transplants can be successfully performed in sublethally irradiated mice with and without ex vivo culture. Long-term donor-type engraftment with sustained chimerism has been demonstrated. Thus, murine neonatal blood grafts can be used as an animal model for cord blood transplantation for gene therapy studies where complete myeloablation is not desirable and partial replacement of defective marrow may be sufficient. Furthermore, the possibility of numerically expanding hematopoietic progenitor cells contained in neonatal blood without affecting their engraftment ability could facilitate use of cord blood grafts in adult recipients.

Animals↗
PubMed1996

Detection of maternal DNA in placental/umbilical cord blood by locus-specific amplification of the noninherited maternal HLA gene.

A critical issue regarding the broader utilization of placental/ umbilical cord blood (PCB) in unrelated bone marrow restoration is the possibility of contamination with maternal lymphocytes capable of immunological reactivity against the eventual recipient. On transplantation, such maternal cells might lead to graft-versus-host disease (GVHD) even if the intended donor's neonatal lymphocytes were unresponsive. We measured the proportion of PCB samples that were contaminated with maternal cells. Placental-maternal sample pairs were selected so that the mother was heterozygous for the DR53 haplotype, whereas the placental sample was DR53-negative. The PCB samples were investigated for the presence of the noninherited maternal gene DRB4, exclusive to the DR53 haplotypes. Locus-specific polymerase chain reaction amplification with DRB4 sequence-specific primers was followed by either gel electrophoresis or blotting and hybridization to an internal sequence DRB4 probe. Polymerase chain reaction products from DNA mixtures containing as low as 0.5 ng of a DRB4-positive DNA control in 1.0 microgram of a DRB4-negative DNA sample (1:2 x 10(3) dilution) showed a visible DRB4 band in agarose gels stained with ethidium bromide. Locus-specific hybridization increased the detection sensitivity to 1:10(5) (0.01 ng of the DRB4-positive DNA control). Control mixtures of known amounts of DRB4-positive and -negative DNA were included in all experiments. Comparison of the thickness of DRB4 bands after electrophoresis and the intensity of the DRB4-specific hybridization signals to the concentration controls allowed a rough estimation of the amount of maternal DNA in the placental blood specimens. A total of 213 PCB samples were tested. By gel electrophoresis, DRB4-specific bands were observed to be as strong or stronger in 23 (10.8%) samples as those in the 1:2 x 10(3) control, and 153 (17.8%) samples were negative in this test. The remaining 37 (17.3%) samples disclosed weaker DRB4 bands, suggesting the presence of maternal genetic material. By hybridization, 81 (38%) samples were positive and 132 were negative for the noninherited maternal gene. Review of the clinical characteristics of the mothers (demographics and labor and delivery information), the newborns (birth weight, sex, and gestational age), and PCB collections (placental weight, white blood cell count, and collected volume) failed to show any significant differences between the units testing positive or negative for the noninherited maternal gene. Thus, transplantable PCB units carry a high probability of having maternal DNA in detectable amounts. Whether this DNA comes from potentially graft-versus-host disease-inducing maternal lymphocytes or whether the putatively transplacentally-acquired maternal cells are immunologically dysfunctional, as in most infants with severe combined immunodeficiency disease, remains to be shown.

Alleles↗
PubMed1996

Placental blood as a source of hematopoietic stem cells for transplantation into unrelated recipients.

BACKGROUND: Transplantation of bone marrow from unrelated donors is limited by a lack of HLA-matched donors and the risk of graft-versus-host disease (GVHD). Placental blood from sibling donors can reconstitute hematopoiesis. We report preliminary results of transplantation using partially HLA-mismatched placental blood from unrelated donors. METHODS: Twenty-five consecutive patients, primarily children, with a variety of malignant and non-malignant conditions received placental blood from unrelated donors and were evaluated for hematologic and immunologic reconstitution and GVHD. HLA matching was performed before transplantation by serologic typing for class I HLA antigens and low-resolution molecular typing for class II HLA alleles. In donor-recipient pairs who differed by no more than one HLA antigen or allele, high-resolution class II HLA typing was done retrospectively. Fordonor-recipient pairs who were mismatched for two HLA antigens or alleles, high-resolution typing was used prospectively to select the best match for HLA-DRB1. RESULTS: Twenty-four of the 25 donor-recipient pairs were discordant for one to three HLA antigens. In 23 of the 25 transplant recipients, the infused hematopoletic stem cells engrafted. Acute grade III GVHD occurred in 2 of the 21 patients who could be evaluated, and 2 patients had chronic GVHD. In vitro proliferative responses of T cells and B cells to plant mitogens were detected 60 days after transplantation. With a median follow-up of 12 1/2 months and a minimal follow-up of 100 days, the overall 100-day survival rate among these patients was 64 percent, and the overall event-free survival was 48 percent. CONCLUSIONS: HLA-mismatched placental blood from unrelated donors is an alternative source of stem cells for hematopoietic reconstitution in children.

Adolescent↗
PubMed1996

A rapid genotype assay for Pla haplotypes.

The method described here results in simple visual analysis of 1, 2, or 3 ethidium bromide-stained bands corresponding to the PlA1, PlA2 or PlA1/A2 phenotypes, respectively. The amplification primers, designed to yield a 711bp product which encompasses exon 2 and substantial intronic sequence both 5' and 3' of the exon enable exquisite resolution of the restriction enzyme digestion products which define the alleles. In addition to prediction of fetal risk of neonatal alloimmune thrombocytopenia using this method, an ethnically heterogeneous pool of platelet donors was screened for the platelet antigen PlA (HPA-1) and gave unequivocal results which should be useful for platelet matching.

Antigens, Human Platelet↗
PubMed1996

Anti-islet autoantibodies detected by monoclonal antibody 1A2: further studies suggesting a role in the pathogenesis of IDDM.

Insulin-dependent diabetes mellitus (IDDM) is associated with autoantibodies to several pancreatic islet antigens. We have described an assay in which autoantibodies displace a radiolabelled monoclonal anti-islet antibody. Sera from 87% of 429 children at time of diagnosis of IDDM were positive, while sera from control groups had much lower prevalences (1.3-19%). Sera from 41.9% of diabetic subjects remained positive after 20 years duration of IDDM. Sera from 23.6% of parents and 37.9% of non-diabetic siblings were positive. Twenty relatives who subsequently developed IDDM had the same prevalence of the antibodies (85%) as did the patients at time of diagnosis. These findings confirm that the autoantibodies detected by monoclonal antibody (mAb) 1A2 are common at the onset of IDDM and their presence prior to the onset of hyperglycaemia suggests that this method may be useful in screening non-diabetic populations. The high prevalence of antibodies in relatives reduces the efficacy for diabetes prediction, but suggests either that generation of these antibodies is an autosomal dominant trait, or that the antigen detected by these antibodies is cross-reactive with a common environmental antigen. Differentiation between these hypotheses will await the identification of the specific islet-cell antigen detected by mAb 1A2.

Adolescent↗
PubMed1996

Stability in controlling viral replication identifies long-term nonprogressors as a distinct subgroup among human immunodeficiency virus type 1-infected persons.

Long-term nonprogressors (LTNPs) of human immunodeficiency virus type 1 (HIV-1) infection are characterized by low levels of HIV-1 replication and viral load. However, it has not been established whether they differ in this regard from progressors from the very early stage of infection. By studying peripheral blood mononuclear cell (PBMC) specimens from a longitudinally monitored cohort of HIV-1-infected men, we found that HIV-1 proviral copy numbers and HIV-1 mRNA expression levels as low or lower than those seen in seven carefully selected LTNPs were commonly observed in specimens collected soon after seroconversion from 28 subjects who became infected while under observation. However, only the LTNPs were able to stably maintain such an efficient viral control over time. Because of the instability of the early control of HIV-1 replication, the predictive value of HIV-1 mRNA expression in PBMCs at postseroconversion was found to be limited but significantly increased during the first year of infection. Besides their diagnostic implications, these data support the idea that LTNPs may be a pathophysiologically distinct subgroup among persons infected with HIV-1.

Cohort Studies↗
PubMed1996

A method to detect McLeod phenotype red blood cells.

It is important to identify the McLeod phenotype in order to differentiate the McLeod syndrome from other causes of acanthocytosis, e.g., chorea acanthocytosis. A proportion of males with the McLeod phenotype have X-linked chronic granulomatous disease. Because anti-Kx + -Km, which is needed for identification, is not readily available, detection of the McLeod phenotype relies on observed weakening of Kell antigens on the individual's red blood cells (RBCs). Identification of McLeod carrier females (obligate heterozygotes) is even more difficult because only a minor subpopulation of RBCs may express the weakened Kell phenotype. RBCs from 12 sets of mother/son or father/daughter pairs were tested by standard hemagglutination tube tests and by flow cytometry using both monoclonal and polyclonal Kell system antibodies. Monoclonal anti-K14 (G10) in tests with RBCs from McLeod males reacted +/- by hemagglutination (control cells 2+) and had a median fluorescence of 6-11 by flow cytometry (control cells 441). Monoclonal anti-k (F7) and human polyclonal anti-k (C30A-1) gave stronger reactions by hemagglutination with RBCs from McLeod males and were not appropriate to differentiate RBCs with the McLeod phenotype from RBCs with normal Kell antigen expression. Crisp mixed-field agglutination was obtained in tests with monoclonal anti-K14 versus RBCs from the 12 obligate carrier females. Flow cytometry using anti-K14 also clearly identified two RBC populations (median fluorescence of 6-11 and 229-382, respectively). Kell system antibodies may vary in their ability to detect a weakened expression of the corresponding antigen on RBCs with the McLeod phenotype by hemagglutination. Antibodies suitable for differentiating McLeod syndrome from other forms of acanthocytosis should be reagents that are preselected after extensive testing. In this study, flow cytometry clearly identified the two RBC populations in McLeod carrier females.

Journal Article↗
PubMed1996

[Aberrant intra-petrous internal carotid artery: apropos of a case].

This article illustrates a case of an aberrant pathway of the petrous portion of an internal carotid artery presenting as a cholesteatoma. This is a case of a 53 y.o man presenting with unilateral otalgia and vertigo. Otoscopic examination revealed a whitish retro-tympanic mass accompanied by a conduction hearing loss mimicking a cholesteatoma. An exploratory tympanotomy was performed. The surgical procedure was interrupted after needle aspiration of the mass suggesting an aberrant course of the petrous portion of the internal carotid artery. Authors report a review of the literature with an emphasis on the differential diagnosis, clinical and paraclinical diagnostic work-up. A thorough knowledge of this anomaly is required to avoid an iatrogenic risk during any otological surgery.

Carotid Artery, Internal↗
PubMed1995

HIV-1 messenger RNA in peripheral blood mononuclear cells as an early marker of risk for progression to AIDS.

OBJECTIVE: To establish human immunodeficiency virus type 1 (HIV-1) messenger RNA (mRNA) expression in peripheral blood mononuclear cells as a marker of risk for progression to the acquired immunodeficiency syndrome (AIDS) in a large cohort of HIV-infected persons followed for a prolonged period. DESIGN: Retrospective testing of cryopreserved, coded specimens. SETTING: Research laboratories at the New York Blood Center and the Rockefeller University. PATIENTS: 150 homosexual men infected with HIV-1 who did not have an AIDS diagnosis at the time of testing. MEASUREMENTS: Multiply spliced and unspliced HIV-1 mRNAs in total peripheral blood mononuclear cell RNA were quantitated using reverse transcriptase-initiated polymerase chain reaction (PCR) and compared with other laboratory data and clinical outcome during the subsequent 8 years. RESULTS: Although HIV-1 mRNA expression generally correlated with immunologic status, it was associated with future disease progression independently of CD4+ cell counts or their rate of decrease at the time of sampling. The association of HIV-1 mRNA with disease progression in persons with CD4+ cell counts higher than the median (> 624 cells/mm3) was particularly noteworthy; further variation in the CD4+ cell counts within this group was not prognostically significant. CONCLUSIONS: The expression of HIV-1 mRNA in peripheral blood mononuclear cells is a strong independent marker for future HIV disease progression, even in persons with normal T-cell subsets.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Processing and cryopreservation of placental/umbilical cord blood for unrelated bone marrow reconstitution.

Clinical evidence of hematopoietic restoration with placental/umbilical cord blood (PCB) grafts indicates that PCB can be a useful source of hematopoietic stem cells for routine bone marrow reconstitution. In the unrelated setting, human leukocyte antigen (HLA)-matched donors must be obtained for candidate patients and, hence, large panels of frozen HLA-typed PCB units must be established. The large volume of unprocessed units, consisting mostly of red blood cells, plasma, and cryopreservation medium, poses a serious difficulty in this effort because storage space in liquid nitrogen is limited and costly. We report here that almost all the hematopoietic colony-forming cells present in PCB units can be recovered in a uniform volume of 20 ml by using rouleaux formation induced by hydroxyethyl starch and centrifugation to reduce the bulk of erythrocytes and plasma and, thus, concentrate leukocytes. This method multiples the number of units that can be stored in the same freezer space as much as 10-fold depending on the format of the storage system. We have also investigated the proportion of functional stem/progenitor cells initially present that are actually available to the recipient when thawed cryopreserved PCB units are infused. Progenitor cell viability is measurably decreased when thawed cells, still suspended in hypertonic cryopreservative solutions, are rapidly mixed with large volumes of isotonic solutions or plasma. The osmotic damage inflicted by the severe solute concentration gradient, however, can be averted by a simple 2-fold dilution after thawing, providing almost total recovery of viable hematopoietic progenitor cells.

Blood Cell Count↗
PubMed1995

Change points in the series of T4 counts prior to AIDS.

The absolute number of T4 cells has been established as an important clinical marker of disease progression to acquired immunodeficiency syndrome (AIDS) in persons infected with human immunodeficiency virus (HIV). Series of T4 counts are analyzed from the 131 homosexual men who entered the New York Blood Center Study in 1984, mostly seropositive for HIV, and who developed AIDS as participants by 1990. These series exhibit a gradual decline of the log(T4) count followed by a more rapid decline close to the time of the development of AIDS. Empirical Bayes and hierarchical Bayes change point models are proposed to estimate the distribution of the time before AIDS when this rapid decline begins. Results using the EM Algorithm and Markov chain Monte Carlo indicate that the mean change point occurs approximately 1 year before diagnosis with a standard deviation of 9 months. Detection of a change point may indicate that an AIDS diagnosis is increasingly likely for an individual HIV-positive but AIDS-free.

Acquired Immunodeficiency Syndrome↗