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Biomedical subjects

N Collins

Publications and source records attributed to N Collins.

At least 73 records · Page 4Linked to original sources

ISHAGE bone marrow processing survey: report on an international information gathering process. International Society for Hematotherapy Graft Engineering.

Significant amounts of information are currently available within the database generated by the responses to the Bone Marrow Processing Survey. As additional Surveys are returned, the data will continue to be entered into a Lotus spreadsheet, until a more sophisticated database with a programmed interface becomes available. The readership is encouraged to enter or edit the databank by returning a completed or amended Survey to the Society. Copies of the form are available from the Society or can be found in the first issue of the Journal of Hematotherapy.

Blood Transfusion, Autologous↗

Basal-cell carcinoma in temperate and tropical Australia.

The clinical features of patients with basal-cell carcinoma (BCC) living in temperate and tropical Australia were studied. In the temperate zone the patients were considerably older on average, men outnumbered women and there were differences between the sexes in the site of the prevalent BCC. In the tropics the patients were significantly younger on average, the male-to-female ratio approached unity and there were no differences between the sexes with regard to the site of the BCC.

Adult↗

Basal cell carcinoma in tropical Australia.

A survey of people with skin cancer in tropical Australia detected a change in site of the prevalent cancer. In the post-war generation more basal cell carcinomas are occurring on the back and fewer on the head and neck. A reversal of the sex ratio was also detected, with more women being afflicted.

Adult↗

Squamous cell carcinoma in southern and northern Australia.

Squamous cell carcinoma (scc) of the skin was studied in two similar populations, one living in the temperate zone of Australia, the other living in the tropics. In the tropics, the patients were significantly younger, the man to woman ratio approached unity, and women had significantly more sccs on the legs. In the temperate zone, men had significantly more on the head and neck, but women had significantly more on the upper and lower limbs.

Adolescent↗

Multiple basal cell carcinoma in tropical Australia.

No association between HLA DR1 and the development of multiple basal cell carcinomas (BCC) was found among patients who had lived at least two-thirds of their lives in the tropics. The percentage of patients with multiple BCCs increased with age; this was different from what has been found in people living in the temperate zone of Australia.

Adult↗

Purification and partial characterization of a human hematopoietic precursor population.

This study reports the development of an assay, the Pre-colony-forming unit (CFU) assay, which detects human hematopoietic precursors. The Pre-CFU assay is based on the observation that precursors to CFU-granulocyte-macrophage (CFU-GM) that are undetectable in clonogenic assays differentiate into CFU-GM preferentially following treatment in suspension culture with recombinant human interleukin-1 alpha (rhIL-1 alpha) combined with rhIL-3. Using the Pre-CFU assay, hematopoietic precursors were detected in human bone marrow depleted of CFU-GM progenitors and differentiated hematopoietic elements via 4-hydroperoxycyclophosphamide treatment coupled with selection for CD34+ cells (4-HCresistant/CD34+ marrow). Additionally, the Pre-CFU assay detected recovery of hematopoiesis substantially earlier than the CFU-GM assay in primates following myeloablation with 5-fluorouracil. The Pre-CFU assay was used to asses purification of a phenotypically defined hematopoietic precursor population, the lin-CD34+ population. The lin-CD34+ population lacks detectable surface markers for T-cell, B-cell, natural killer cell, and myeloid lineage, possesses the CD34 antigen, is devoid of CFU-GM progenitors, and yields Pre-CFU assay values comparable with 4-HCresistant/CD34+ marrow. Using a combination of phenotypic analysis and Pre-CFU assay analysis, the action of rhIL-1 alpha plus rhIL-3 treatment on lin-CD34+ cells was further characterized. The data indicate that rhIL-1 alpha plus rhIL-3 treatment induces proliferation and differentiation of early hematopoietic precursors into progenitors and terminally differentiated cells, without inducing a significant expansion of the precursor population itself.

Animals↗

A prospective study to evaluate the dose of vitamin D required to correct low 25-hydroxyvitamin D levels, calcium, and alkaline phosphatase in patients at risk of developing antiepileptic drug-induced osteomalacia.

The dose of vitamin D3 required to maintain normal serum 25-hydroxyvitamin D levels in epileptic patients was evaluated in a prospective study. Patients were divided into two groups, comprising 14 institutionalized and 18 non-institutionalized subjects; they were taking carbamazepine, phenytoin and phenobarbitone, alone or in combination. The study was divided into a dose titration stage and a further period of assessment on a fixed dose after attainment of normal serum 25-hydroxyvitamin D levels. Seventeen of the 18 non-institutionalized patients achieved normal levels over a period of 12 months; the remaining patient became normal after 15 months. The dose required to achieve normal levels ranged from 400 to 4000 IU/day; three patients required less than 2400 IU vitamin D3, 12 required 2400 IU and three required greater than 2400 IU. All institutionalized patients achieved normal levels over a period of 12 months; six patients required less than 2400 IU, six required 2400 IU and two required greater than 2400 IU vitamin D3. Raised alkaline phosphatase levels occurred in 11 patients, and reverted to normal in six patients during the initial return of 25-hydroxyvitamin D levels to normal. During the second 12 months, when patients were taking a fixed dose of vitamin D3, alkaline phosphatase increased in five patients who had achieved normal levels. During this phase normal 25-hydroxyvitamin D levels were not maintained in five patients. There was a significant seasonal variation of 25-hydroxyvitamin D levels institutionalized patients, being highest in June and lowest in December. Our findings show that while there was a wide range in the dose required to achieve normal serum 25-hydroxyvitamin D levels--between 400 and 4000 IU/day--78 per cent of patients responded to a dose of 2400 IU/day.

Adolescent↗

Loss of tolerance associated with disappearance of B cells in a patient sequentially transplanted with paternal and maternal bone marrow for the treatment of severe combined immunodeficiency disease.

We have studied the tolerance of engrafted T cells from a severe combined immunodeficiency disease patient sequentially transplanted with T-cell-depleted bone marrow from both HLA haploidentical parents. The T cells from this patient were shown by HLA typing and cytogenetic analysis to be of material origin (donor of the second graft) while HLA typing of peripheral E--populations and of an Epstein-Barr virus-transformed B-cell line established 2 1/2 years after transplantation revealed the presence of host, maternal, and paternal (donor of the first graft) HLA antigens. When tested at 30 and 60 months after the last transplant, engrafted T cells from this patient had only weak mixed lymphocyte culture reactivity to paternal cells which could be inhibited by monoclonal antibodies to HLA-DQ and DR but not by anti-DP. T cells obtained 60 months after transplant were stimulated with paternal cells in both bulk and limiting dilution cultures and failed to generate typical allocytotoxic cells to paternal T- or B-cell targets. Mixed lymphocyte cultures performed at 71 months revealed an increased proliferative response by patient cells to paternal antigens; however, the engrafted T cells remained tolerant to maternal and host antigens. Limiting dilution analysis performed at this time revealed the presence of cytolytic cells directed to paternal antigens. There were no detectable B cells (only identified source of paternal antigen) as measured by immunofluorescent analysis of peripheral blood, nor any evidence of B-cell function as assessed by in vitro assays (proliferation to staphylococcus aureus Cowen strain A and mitogen-stimulated immunoglobulin production) or in vivo production of serum immunoglobulin at 60 and 71 months. The appearance of alloreactivity associated with the loss of B cells in this patient further supports the conclusion that the maintenance of tolerance to major histocompatibility complex disparate cells requires the continued in vivo presence of cells bearing the tolerizing antigens.

Antibody Formation↗

Bare lymphocyte syndrome: altered HLA class II expression in B cell lines derived from two patients.

Types II and III bare lymphocyte syndrome (BLS) are severe or lethal congenital immunodeficiencies characterized by defective cell surface expression of HLA class II antigens. We have analyzed by Southern and Northern blotting B-lymphoblastoid cell lines derived by Epstein-Barr virus (EBV) transformation from peripheral blood lymphocytes of two unrelated BLS patients and their families. While DNA analyses of both families showed no indication of rearrangement or alteration of HLA region genes, class II mRNAs were virtually absent in the patients' cell lines (BLS-1 and BLS-2). This is consistent with previous observations of different BLS patients and their families. An exception to the absence of class II mRNAs in BLS was the detection of low quantities of HLA-DQ alpha transcripts in the cell lines BLS-1. This finding provides further evidence that factors regulating HLA-DQ expression may differ from those governing expression of the other class II genes.

B-Lymphocytes↗

Characterization of B cells in severe combined immunodeficiency disease.

The circulating lymphoid cells of eight consecutive untreated infants with severe combined immunodeficiency disease (SCID) with B cells were analyzed for surface marker expression and function. The B cells of these children expressed sIg, HLA-DR, CD19 (B4), CD20 (B1), CD21 (B2), Leu-8, and lacked expression of CD10 (CALLA), as do normal peripheral blood B lymphocytes. SCID B cells also expressed antigens that are normally absent or present on only a minor subset of circulating adult B lymphocytes, including CD1c (M241), CD38 (OKT10), CD23 (PL13), with or without concomitant CD5 (Leu-1) expression. The B cells of these children were capable of proliferating in vitro when stimulated with Staphylococcus aureus Cowan I. However, in the presence of pokeweed mitogen, S. aureus Cowan I, and normal T cells, the sIg+ cells of these children produced only IgM. Studies performed on normal B cells obtained from cord blood, young children, and adults reveal that whereas cord blood B cells are predominantly CD1c, CD38, and CD23 positive, B-cell expression of these antigens decreases with age. Cord blood B cells, similar to SCID B cells, produce only IgM when stimulated in vitro with pokeweed mitogen and S. aureus Cowan I. Based on these observations, we hypothesize that SCID B cells represent a population of B cells present during normal B-cell ontogeny which becomes a minor subset when an individual develops full immunologic competence.

Antibodies, Monoclonal↗

Chronic extensive necrotizing abscess of the scalp.

Chronic subgaleal abscesses have been extremely rare since the advent of antimicrobial therapy. The majority of reported cases have occurred as acute infections following traumatic scalp lacerations or needle electrode insertion for fetal monitoring. The rich blood supply of the head makes widespread infection from a scalp surgical wound a very unlikely occurrence. Most acute infections of the scalp result in complete resolution with adequate early treatment. However, extensive purulent fibrosis of the scalp remains a potentially serious surgical complication. We report 2 cases of chronic necrotizing abscess of the scalp associated with a postsurgical scalp ulcer. The inflammatory process caused extensive necrotizing fibrosis (up to 2.5 cm thick) of the entire undersurface of the scalp and involved both the galea aponeurotica and the periosteum. We discuss the unique pathological features of this entity along with recommendations for its operative management and suggestions for flap design.

Abscess↗

M241 (CD1) expression on B lymphocytes.

The human thymus leukemia-like antigens (CD1a-c) consist of three similar glycoproteins found on subpopulations of normal thymocytes, T cell acute leukemias, and cutaneous dendritic cells. The CD1c antigen recognized by the M241 monoclonal antibody was detected on the circulating mononuclear cells of three children with severe combined immunodeficiency disease (SCID). Two-color immunofluorescence analysis demonstrated that M241 expression (43 to 95%) was limited to cells expressing the B cell-restricted antigens B4 (CD19), B1 (CD20), and surface immunoglobulin. To confirm M241 expression on normal cells of the B lineage rather than aberrant expression limited to SCID B cells, its expression was demonstrated serologically and biochemically on purified B cells from spleen, tonsil, and peripheral blood. Parallel analyses with monoclonal antibodies NA1/34 and 4A76 demonstrated that the CD1a and CD1b molecules were negative on all B cells that were studied. It has been hypothesized that the CD1 molecules represent the human counterpart of the murine thymus leukemia antigens due to their similar size, limited tissue distribution, and association with beta 2-microglobulin. This study suggests that a subset of CD1 antigens detected by M241 (CD1c) may represent a human analog of a murine Qa antigen due to its extended distribution on normal peripheral B cells.

Antibodies, Monoclonal↗

Evaluation of HLA-haplotype disparate parental marrow grafts depleted of T lymphocytes by differential agglutination with a soybean lectin and E-rosette depletion for the treatment of severe combined immunodeficiency.

The factors that impact upon successful bone marrow transplantation leading to immunologic reconstitution in severe combined immune deficiency (SCID). Wiskott-Aldrich syndrome, and in other lethal congenital immunodeficiencies are reviewed. Evidence is presented that graft-versus-host disease (GVHD) can be abrogated by the depletion of T cells, even from histoincompatible marrow grafts. However, graft resistance or restricted immune reconstitution has been observed with significant frequency. The bases for T cell reconstitution and limitations in B cell humoral immune recovery in the postgrafting period are reviewed, together with emerging evidence that pretransplant cytoreduction might obviate some of these problems.

Agglutination Tests↗