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P Rubinstein

Publications and source records attributed to P Rubinstein.

At least 19 recordsLinked to original sources

Growth characteristics and expansion of human umbilical cord blood and estimation of its potential for transplantation in adults.

We estimated whether single collections of cord blood contained sufficient cells for hematopoietic engraftment of adults by evaluating numbers of cord blood and adult bone marrow myeloid progenitor cells (MPCs) as detected in vitro with steel factor (SLF) and hematopoietic colony-stimulating factors (CSFs). SLF plus granulocyte-macrophage (GM)-CSF detected 8- to 11-fold more cord blood GM progenitors [colony-forming units (CFU)-GM] than cells stimulated with GM-CSF or 5637 conditioned medium (CM), growth factors previously used to estimate cord blood CFU-GM numbers. SLF plus erythropoietin (Epo) plus interleukin 3 (IL-3) enhanced detection of cord blood multipotential (CFU-GEMM) progenitors 15-fold compared to stimulation with Epo plus IL-3. Under the same conditions, bone marrow CFU-GM and CFU-GEMM were only enhanced in detection 2- to 4- and 6- to 8-fold. Increased detection of cord blood CFU-GEMM correlated directly with decreased detection of cord blood erythroid burst-forming units (BFU-E). In contrast, adult bone marrow CFU-GEMM and BFU-E numbers were both enhanced by SLF plus Epo plus IL-3. This suggests that most cord blood BFU-E may actually be CFU-GEMM. Cord blood collections (n = 17) contained numbers of MPCs (especially CFU-GM) similar to the number found in nine autologous bone marrow collections. To assess additional sources of MPCs, the peripheral blood of 1-day-old infants was assessed. However, average concentrations of MPCs circulating in these infants were only 30-46% that in their cord blood. Expansion of cord blood MPCs was also evaluated. Incubation of cord blood cells for 7 days with SLF resulted in 7.9-, 2.2-, and 2.7-fold increases in numbers of CFU-GM, BFU-E, and CFU-GEMM compared to starting numbers; addition of a CSF with SLF resulted in even greater expansion of MPCs. The results suggest that cord blood contains a larger number of early profile MPCs than previously recognized and that there are probably sufficient numbers of cells in a single cord blood collection to engraft an adult. Although the expansion data must be considered with caution, as human marrow repopulating cells cannot be assessed directly, in vitro expansion of cord blood stem and progenitor cells may be feasible for clinical transplantation.

Age Factors

Glyoxalase 1: a possible 'null' allele.

A three-generation family, ascertained through the presence of two diabetic sibs, provides segregation data suggestive of the existence of a null allele at the glyoxalase (GLO) locus. This conclusion is supported by the GLO 1 phenotype in two children from a GLO 2 father. These two children inherited the same paternal HLA allele, while two other sibs received GLO 2 with the other paternal HLA haplotype. The rest of the pedigree is in agreement with this suggestion, while the segregation of all other informative markers does not suggest nonpaternity.

Alleles

Murine complement component 3: genetic variation and linkage to H-2.

Two electrophoretic variants of murine complement component 3 (C3) were detected by using high-voltage electrophoresis of fresh mouse serum in agarose gels. Most of the inbred strains tested were homozygous for the S allele (for the slow-migrating variant); only four out of 46 strains had the alternative F allele (fast variant). Pen-bred Swiss-Webster animals belonged to one of three phenotypes--S, F, or SF--and the genes responsible for this variation segregated in a strictly Mendelian manner. In three such crosses, with 5* offspring, C3 segregated with H-2 in 46 instances, corresponding to a recombination frequency of approximately equal to 0.12.

Animals

Quantitation of HLA-D differences.

The predictability of MLC non-reactivity by HTC typing was tested in a single checkerboard experiment which involved 39 unrelated individuals belonging to 12 different groups of HLA-D identical phenotypes. The strength of one-way MLC reactions in all possible responder-stimulator combinations (39 X 39) was quantitated by the Linear Clustering Analysis Program. Individuals who, by HTC typing, were identical for two HLA-D antigens gave 51% negative, 36% intermediate and 13% strong positive MLC responses. Identity for only one HLA-D antigen resulted in 3% negative, 40% intermediate and 57% strong MLC reactions. When no HLA-D antigen was shared, 88% of the reactions were strongly positive. HLA-D antigens behaved as equipotent stimulators in MLC between half-identical pairs. The only exception consisted of the higher frequency of weak responses displayed by the Dw5 positive individuals against stimulators differing by LD107. The same pattern was observed when LD107 homozygous cells were used as stimulators, suggesting that determinants of this specificity might be partially included in Dw5.

Epitopes

Genetics of juvenile diabetes mellitus. A recessive gene closely linked to HLA D and with 50 per cent penetrance.

We investigated the genetic predisposition to juvenile diabetes in the families of 31 index cases in relation to the inheritance of the HLA system. The diabetes-predisposing gene was found to be recessive because the diabetic sibs in index cases shared both their HLA genes with a significantly increased frequency. Penetrance was estimated at 50 per cent because half the HLA-identical sibs in index cases were diabetic. These conclusions fit with published observations that the risk to sibs of patients is about 100 per cent, when both parents are normal. In three informative cases of recombination within HLA the predisposing gene traveled with the HLA D segment of the recombinant haplotype. We prepared tables for the computation of risks to relatives, based on the hypothesis of recessivity, HLA linkage and 50 per cent penetrance.

Adolescent

Biochemical genetics of MN.

Quantitative hemagglutination studies of the MN-hemizygous (M/-) patient and his family reported by German et al. are given together with data on the electrophoretic mobility of their red cells. These results, and those obtained on the cells of a donor of the MU phenotype (MU=M+N-S-s-U+); Mu=M+N-S-s-U), demonstrate a series of shortcomings in the current 'precursor transferase' theory of the biochemical genetics of MN antigens. Another theory is proposed, according to which the effects of the MN genes take place exclusively in the protein part of the glycopeptide. The MN proteins would carry acceptor sites for the antigenic oligosaccharides which are put together by enzymes genetically independent of MN. In M glycoproteins, the acceptor sites are close to each other, in doublets, while in N they are all separate. This model is shown to apply successfully to several difficult problems in MN.

Electrophoresis

Results of miconazole therapy in twenty-eight patients with paracoccidioidomycosis (South American blastomycosis).

Results are presented of treatment with miconazole, orally and intravenously, in patients with paracoccidioidomycosis. Twenty-eight male patients aged from 34 to 66 years and exhibiting various clinical forms of the disease were studied. Twenty-five came from endemic areas in north east Argentina (Chaco, Formosa, Misiones, Corrientes and northern Santa Fe) and the remaining three from Paraguay. Twenty patients were engaged in agricultural work or at woodmills. single or multiple lesions were observed in 24 cases. Thirteen were suffering from infection of the larynx and in two of them a tracheotomy was necessary. Twenty-three showed pulmonary lesions on X-rays. Twelve had ganglionic lesions, eight had cutaneous lesions and one patient had osteoarthritis of the knee. One patient had hepatomegaly which was unrelated to chronic alcoholism. Fourteen patients had received previous treatments such as sulphonamides and amphotericin B (7 cases); sulphonamides (3), sulphonamides and the combination sulfamethoxazole + trimethoprim (3), and one patient had received all three medications. All patients had relapsed before starting miconazole therapy. Diagnosis was established by the presence of P. brasiliensis in all cases, recovered either from cutaneous or mucosal biopsy samples or from the sputum. Complement fixation tests were positive in all patients at the onset of the treatment and the immunodiffusion reactions showed precipitation bands in 27/28 patients. Skin tests with P. brasiliensis antigens proved to be positive in 18 cases and negative in 10. The erythrocyte sedimentation rate was markedly accelerated in 22 patients (greater than 20 mm in the first hour).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral

Complete typing of the HLA region in families. III. Analysis of responses in the primed lymphocyte test (PLT).

LCA, a rapid and efficient computer method to allocate blastogenic responses to positive and negative clusters, is described. The method involves the selection of a partition level for an ordered array of values, such that the resulting two clusters have minimal "within-cluster" variances. Individuals to whom the program assigned the same two HLA-D antigens were MLC-identical (cluster 0) in 50% of the cases. This proportion was lower for HLA-D-identical pairs that typed for Dw4 and/or Dw7, indicating that these antigens are less well defined than the rest. PLTs were less efficient than HTCs in HLA-D typing due to the induction of extra (non-HLA-D determined) responses in the higher cluster.

Computers