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Biomedical subjects

R Sparkes

Publications and source records attributed to R Sparkes.

35 records · Page 2Linked to original sources
PubMed1987

Demonstrated paternity in spite of severe idiopathic oligospermia.

In this study we report on a successful pregnancy in the spouse of a man who, on repeated occasions, spaced over 3 years, presented with a mean sperm concentration of less than 200,000 sperm/ml. Serum was drawn from the father, mother, and daughter for polymorphic gene marker analysis. The calculation of relative probability of paternity with the use of gene frequencies for whites gave a figure of 99.9% that our patient is the father of the child.

Adult↗
PubMed1984

Location of the retinoblastoma susceptibility gene(s) and the human esterase D locus.

Retinoblastoma occurs with increased frequency in children born with a deletion of the long arm of chromosome 13. Recent reviews have noted that the region 13q14 is consistently deleted in documented cases. Prometaphase and late prophase banding allowed Yunis and Ramsay to determine that a deletion in one patient included the sub-bands q14 . 12, q14 . 13, and q14 . 2, and a portion of q14 . 11 and q14 . 3. We report the results of similar cytogenetic techniques applied in the case of a 26 month old Caucasian female with unilateral retinoblastoma, moderate developmental delay, and subtle dysmorphology. Prometaphase banding of cultured skin fibroblasts revealed the karyotype: mos46,XX/46,XX,del(13)(q13 . 1q14 . 11). Only the sub-band q14 . 11 is deleted in both our patient and that of Yunis and Ramsay. The results are consistent with the localisation of the retinoblastoma susceptibility gene(s) in the sub-band 13q14 . 11. Electrophoretic analysis and activity assays of red blood cell esterase D are consistent with hemizygous expression of that marker in our proband. Comparison with published esterase D analyses in families with retinoblastoma permits the assignment of the esterase D locus to that same sub-band, 13q14 . 11.

Carboxylesterase↗
PubMed1981

Prevention of graft rejection following bone marrow transplantation.

Bone marrow transplantation from an HLA-identical sibling is increasingly used in the treatment of severe aplastic anemia. One major problem with this approach is graft rejection that occurs in 25%-60% of patients conditioned for transplantation with cyclophosphamide. At most transplant centers it has been difficult to accurately identify patients at high risk for graft rejection. We studied a conditioning regimen of cyclophosphamide (200 mg per kg) and low-dose total body irradiation (3 Gy; equivalent to 300 rad) in 23 consecutive unselected patients with aplastic anemia followed for a minimum of 6 mo. There was only one episode of graft rejection. Graft-versus-host disease and interstitial pneumonitis were not increased by the more intensive conditioning regimen. Actuarial survival was 61% at 1 yr and 49% at 2.5 yr. Cyclophosphamide and low-dose total body irradiation is an effective conditioning regimen in patients with aplastic anemia. It may be particularly useful when accurate predictive tests of graft rejection are not available as is the case in most transplant centers.

Actuarial Analysis↗
PubMed1980

An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1).

A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cells, while the parent cells and several of its clones are at the myeloblast and promyelocyte stages of development. The variant cells do not respond to colony-stimulating factor (CSF), and they do not express the human la antigen, nor a recently characterized AML antigen. The parent KG-1 cells are stimulated to proliferate in the presence of CSF and the cells express the la and AML antigen. Variant AML cell lines, such as KG-1a, will be useful in vitro models for investigating cellular response to CSF and for studying antigen expression in leukemic cells.

Cell Line↗
PubMed1977

Bone-marrow transplantation in acute leukaemia.

Survival in 33 patients with resistant leukaemia treated by marrow transplantation was compared with that of 37 matched patients treated by conventional and experimental chemotherapy. All patients in the transplant group were rendered free of detectable leukaemia for periods of from 36 days to more than 2 1/2 years, while only 6 patients in the chemotherapy group achieved a haematological remission. Overall survival in both groups was poor; however, 5 patients (15%) in the transplant group remain alive and in haematological remission 1--2 1/2 years after transplantation, while no patient in the chemotherapy group survived longer than 13 months. Bone-marrow transplantation appears to offer a small but distinct possibility of long-term survival in patients with acute leukaemia resistant to conventional therapy.

Adolescent↗
PubMed1977

Hematopoietic engraftment following transplantation of bone marrow cells carrying a Philadelphia (Ph')-like chromosome.

A phenotypically normal donor for bone marrow transplantation was found to have a previously unreported karyotype, 46, XY, t(18q+;22q-), resulting in a Ph'-like chromosome. Identification of the Ph'-like chromosome in cultures of skin fibroblasts, phytohemaglutinin-stimulated peripheral blood cells, and bone marrow cells from the marrow donor, but not in cell cultures from siblings or parents, indicated that it represented an acquired somatic mutation. Demonstration of the Ph'-like chromosome in the marrow graft recipient's blood and bone marrow cells after transplantation provided a unique and definitive marker of engraftment. Hematopoiesis appeared normal in both the donor and recipient after transplantation. This study indicates that a mutation creating a Ph'-like chromosome in hematopoietic cells need not produce hematologic abnormality. Presence of this translocation did not appear to interfere with normal hematopoietic or lymphoid differentiation and replication in the transplant setting.

Adult↗
PubMed1977

Experience with incompatible maternal donors for bone marrow transplantation.

Marrow transplantation in aplastic anemia and leukemia has generally been limited to siblings who have been histocompatible at both the serological (A and B) and lymphocyte determined (D or MLC) loci of the HLA system. We studied three male patients, two with aplastic anemia and one with acute myelogenous leukemia, who received transplants from their histoincompatible mothers. MLC studies between donors and recipients showed varying degrees of stimulation. Definite engraftment occurred in one patient and transient engraftment in another. Engraftment in the third patient could not be evaluated. In the patient with sustained engraftment, there was clinical evidence of severe graft versus host disease (GVHD) however, this was not substantiated by histologic findings. This preliminary study suggests that MLC incompatibility may be more of an indicator of the risk of GVHD than of bone marrow rejection. If more effective control of GVHD can be accomplished, marrow transplantation between MLC-reactive individuals may become feasible.

Adult↗
PubMed1977

Sensitization against non-HLA antigens following bone marrow graft rejection.

A patient with severe aplastic anemia rejected consecutive bone marrow transplants from two HLA-identical sibling donors. Following rejection, the patient developed antibodies that reacted strongly against donor lymphocytes in the complement-dependent cytotoxicity assay. Whereas the reactivity was initially directed specifically against the first marrow donor, cells of both donors and most unrelated individuals were killed by sera obtained after the second injection. These sera were also cytotoxic to the patient's own pre-transplant cells but not to her autologous post-transplant lymphocytes.

Adult↗
PubMed1977

ABO blood group system and bone marrow transplantation.

The role of the ABO blood group system in determining the outcome of bone marrow transplantation was investigated in 53 patients with aplastic anemia and acute leukemia grafted from HLA-identical siblings. There was no correlation between ABO compatibility and marrow engraftment, graft rejection, or graft-versus-host disease. In 5 recipients with antibodies prior to transplantation to antigens of the ABH system present on the cells of their donors, plasma exchange and antibody absorption in vivo were effective in permitting engraftment of ABO-incompatible bone marrow. These findings indicate that the ABO system is not a clinically significant barrier to successful bone marrow transplantation in otherwise histocompatible individuals.

ABO Blood-Group System↗
PubMed1976

Successful bone marrow transplantation against mixed lymphocyte culture barrier.

If bone marrow transplantation is to become widely applicable in the treatment of patients with leukemia and aplastic anemia, the necessity to have a perfectly histocompatible donor must be overcome. In an effort to define the roles of HL-A type and mixed lymphocyte culture (MLC) reactivity in the determination of successful engraftment and the occurrence of graftversus-host disease (GVHD), we have attempted transplantation of a child with acute myeloblastic leukemia (AML) using an HL-A identical, MLC-reactive sibling donor. Successful engraftment has been accomplished, as documented by the appearance of multiple donor genetic markers in the recipient. There is no evidence of severe GVHD. The recipient is alive, without evidence of leukemia, and has returned to full activities 9 mo after transplantation. The recipient now produces lymphocytes, which have the MLC reactivity that characterize the donor's lymphocytes, rather than that of her own pretransplant lymphocytes. This experience demonstrates that successful bone marrow transplantation in patients with leukemia can be accomplished in the face of MLC reactivity.

Adolescent↗
PubMed1975

Bone marrow transplantation between mixed lymphocyte culture-reactive individuals.

A 13-year-old boy with acute myelogenous leukemia resistant to conventional chemotherapy received a bone marrow transplant from his HL-A-identical, mixed lymphocyte culture-reactive sister. The recipient was prepared for transplantation with cyclophosphamide and total body irradiation. Despite cytogenetic evidence of engraftment, graft-versus-host disease was not observed. The patient died 38 days post-transplantation of Gram-negative bacteremia sepsis and recurrent leukemia of recipient origin.

Adolescent↗