PubMed Health⌕ Search

Biomedical subjects

D S Hummell

Publications and source records attributed to D S Hummell.

15 recordsLinked to original sources
PubMed2000

Scurvy presenting as painful gait with bruising in a young boy.

A case of scurvy occurred in an apparently well-nourished 5-year-old boy with normal growth parameters. Only after the diagnosis of scurvy was raised on clinical grounds did we discover the peculiar dietary habits that were responsible for his deficiency of ascorbic acid. His case is a reminder to the clinician that nutritionally based disease may occur in any socioeconomic setting and that nutritional screening remains an important part of every child's general health care.

Ascorbic Acid↗
PubMed1998

Complete DiGeorge syndrome: persistence of profound immunodeficiency.

OBJECTIVE: DiGeorge syndrome is characterized by developmental defects of the heart, parathyroid glands, and thymus. The objective of this study was to determine whether T-cell function spontaneously improves in patients with DiGeorge syndrome who have profoundly depressed T-cell proliferative responses to mitogens at presentation, regardless of the T-cell count. STUDY DESIGN: We conducted a retrospective chart review of eight patients with DiGeorge syndrome who had no proliferative responses to mitogens on presentation. RESULTS: Despite lack of responsiveness of the patients' peripheral blood lymphocytes to mitogens, T cells were occasionally detected, and the patients' cells often responded to IL-2 and in mixed lymphocyte reactions. Unresponsiveness to mitogens and clinical immunodeficiency persisted without immune-based therapy. One patient is alive and well after immunoreconstitution from thymic transplantation. The others either died early of complications of their disease such as gastroesophageal reflux with aspiration (2 patients) or infection (2 patients) or died after attempts at immunorestorative therapy with IL-2, thymus transplantation, or bone marrow transplantation (3 patients). CONCLUSION: Eight patients with DiGeorge syndrome who were first seen with no mitogen responsiveness did not improve spontaneously. We recommend HLA-identical bone marrow transplantation or thymic transplantation for these patients as soon as the diagnosis is confirmed.

Bone Marrow Transplantation↗
PubMed1994

Increased interleukin-6 (IL-6) production in a young child with clinical and pathologic features of multicentric Castleman's disease.

A 21-month-old boy presented with a papular rash, lymphoadenopathy, and splenomegaly. He developed symmetric polyarthritis, fever, and progressive glomerulonephritis. Serologies for viral agents including HIV were negative. Antinuclear antibody was transiently positive, but no anti-DNA antibodies were present. CH50 and serum C3 values were low. Biopsies of skin, kidney, bone marrow, and lymph node were obtained. There was a perivascular and periadnexal lymphocytic infiltrate in the skin, with a normal epidermis. Renal biopsy showed proliferative mesangial glomerulonephritis. Bone marrow showed an increased number of plasma cells. Lymph node showed histologic changes described in multicentric Castleman's disease including marked follicular hyperplasia, vascular proliferation, and interfollicular expansion with numerous plasma cells. IL-6 mRNA was demonstrated in cells in the marginal zone and interfollicular regions of the node by in situ hybridization. Likewise, the serum IL-6 level was elevated during a clinical exacerbation of the patient's nephritis. These data suggest an underlying lymphoproliferative disorder, such as Castleman's disease, with overproduction of IL-6 resulting in systemic features of the disease, including glomerulonephritis.

Castleman Disease↗
PubMed1994

The role of T-cell receptors in health and disease.

The progress made in the last several years in understanding the biology of the human T-cell receptor has enabled the start of the formidable task of deciphering the mechanisms that result in the pathogenesis of several important disease states in man. The ability to clone T-cells, and to identify TCR utilization by genetic techniques, has greatly enhanced our ability to diagnose T-cell malignancy and follow its response to treatment. The phenomenon of superantigen activation of TCR has improved our understanding of certain disorders associated with infections in humans. We are now prepared to use new knowledge to begin to dissect the role of T-cells in initiating and perpetuating human autoimmune disease. However, several impediments to progress must first be overcome. One of the most problematic is our failure to identify autoantigens that are relevant to specific disease states. Experimental approaches to the analysis of TCR in humans are complicated by the high degree of genetic variability present in our outbred population. We also currently lack an accurate understanding of the structural basis of TCR/MHC interactions, and we therefore have difficulty translating the relationship of linear TCR gene sequence data to three-dimensional structure. Further progress in understanding the role of the TCR in normal human immune recognition and in disease states will be made when science is successful in bypassing these obstacles.

Autoimmune Diseases↗
PubMed1993

Coordinate transcriptional control of murine endogenous retrovirus and Ig genes during B cell differentiation.

Proliferation and differentiation of B lymphocytes are usually concurrent but independently regulated events. Anti-mu treatment of murine B lymphocytes stimulated with LPS provides a model system in which proliferation and differentiation may be independently studied. This treatment causes enhanced proliferation but with coordinate suppression of transcription of a family of unrelated genes including those for Ig heavy and light chains, J chain, and endogenous murine leukemia virus (MuLV) sequences. We show that in comparison to B lymphocytes stimulated with LPS alone cells stimulated with a combination of anti-mu and LPS exhibit relatively increased amounts of a nuclear binding factor(s), NF mu E1, which interacts with the B (mu E1) site of the IgH enhancer; binding is strongly inhibited by a synthetic probe of the B sequence. A negative regulatory sequence contained within the upstream conserved region (UCR) of the MuLV long terminal repeat (LTR) is identical to the complement of mu E1 in eight of nine bases and inhibits binding of NF mu E1 to the IgH enhancer probe. The mu E1 site is also present 3' to the kappa-light chain gene; binding of this sequence to a repressor protein may coordinately suppress the transcription of mu, kappa, and MuLV genes. Others have reported that the cDNA encoding NF mu E1, also known as mu EBP-B, CF-1, and YY-1, predicts a protein with structural features consistent with variable function as either a transcriptional activator or repressor.

Animals↗
PubMed1993

Novel splicing, missense, and deletion mutations in seven adenosine deaminase-deficient patients with late/delayed onset of combined immunodeficiency disease. Contribution of genotype to phenotype.

We examined the genetic basis for adenosine deaminase (ADA) deficiency in seven patients with late/delayed onset of immunodeficiency, an underdiagnosed and relatively unstudied condition. Deoxyadenosine-mediated metabolic abnormalities were less severe than in the usual, early-onset disorder. Six patients were compound heterozygotes; 7 of 10 mutations found were novel, including one deletion (delta 1019-1020), three missense (Arg156 > His, Arg101 > Leu, Val177 > Met), and three splicing defects (IVS 5, 5'ss T+6 > A; IVS 10, 5'ss G+1 > A; IVS 10, 3'ss G-34 > A). Four of the mutations generated stop signals at codons 131, 321, 334, and 348; transcripts of all but the last, due to delta 1019-1020, were severely reduced. delta 1019-1020 (like delta 955-959, found in one patient and apparently recurrent) is at a short deletional hot spot. Arg156 > His, the product of which had detectable activity, was found in three patients whose second alleles were unlikely to yield active ADA. The oldest patient diagnosed was homozygous for a single base change in intron 10, which activates a cryptic splice acceptor, resulting in a protein with 100 extra amino acids. We speculate that this "macro ADA," as well as the Arg156 > His, Arg101 > Leu, Ser291 > Leu, and delta 1019-1020 products, may contribute to mild phenotype. Tissue-specific variation in splicing efficiency may also ameliorate disease severity in patients with splicing mutations.

Adenosine Deaminase↗
PubMed1992

Cellular infiltration of the vitreous in a patient with X-linked immunodeficiency with increased IgM.

We studied visual impairment caused by benign lymphoid infiltration of the vitreous bilaterally, as a complication of a primary immunodeficiency, X-linked immunodeficiency with increased IgM in an 8-year-old boy. Immunophenotyping of a vitreous aspirate showed a mixed cell population, including lymphocytes (T helper, suppressor-cytotoxic T cells, and B cells) and macrophages. Cultures of the vitreous were negative for bacterial or fungal pathogens. The vitreous infiltrates have been resistant to treatment with corticosteroids and cytotoxic agents.

Agammaglobulinemia↗
PubMed1991

Identification of novel B-lineage cells in human fetal bone marrow that coexpress CD7.

In the present study we used multiparameter flow cytometry and cell sorting to evaluate fetal bone marrow, a rich source of cells early in lymphoid development. We found CD7 to be expressed on a subset of CD19+ cells, including some that had matured to cytoplasmic mu+ (pre-B) and surface mu+ (B) cells. In addition, a less mature CD7+19+ population was characterized as mu- and CD34+/-. The CD7+19+ population was clearly distinct from the mature T cells. The CD7+19+ cells were negative for nuclear TdT in contrast to CD7-19+ cells, which frequently contained TdT. CD10, which is coexpressed on the cell surface of more than 90% of CD19+ lymphocytes, was detected in a minority of CD7+19+ lymphocytes. The CD7+19+34+ cell population may be B-lineage committed, or may represent uncommitted lymphoid precursors. The biologic role of the expression of CD7 on immature and mature cells, including those of the B lineage, may indicate (1) the presence of CD7+19+ lymphoid precursor cells and/or (2) an alternate pathway of B-cell development, in which cells coexpress CD7 with other B-lineage markers.

Antigens, CD↗
PubMed1988

Differentiation of human B lymphocyte subpopulations induced by an alloreactive helper T-cell clone.

We have used cloned alloreactive helper T cells to determine if direct T cell-B cell interaction can induce differentiation of human peripheral blood B cells which do not respond to pokeweed mitogen (PWM). T-cell clone 2F8 was derived from a one-way mixed lymphocyte reaction. 2F8 cells are T3+T4+T8-IL-2R+ and proliferate in response to irradiated stimulator cells, but not autologous cells, in the absence of exogenous interleukin-2. 2F8 cells provide allospecific help for polyclonal proliferation and differentiation of B cells in the absence of any other stimulus. The magnitude of this response is comparable to that of the response of the same B cells to PWM and fresh autologous T cells. 2F8 cells could also provide nonspecific help for unrelated donor B cells in the presence of PWM, with no requirement for costimulation by irradiated stimulator cells. Allospecific stimulation of B cells was completely inhibited by antibodies to class II major histocompatibility complex (MHC) framework determinants and was abrogated by 1000-rad irradiation. Cloned 2F8 T cells stimulated differentiation of both small, high-density B cells and larger B cells, generating up to 30% plasma cells with either fraction. B cells forming rosettes with mouse erythrocytes were also induced to differentiate by the helper T cell clone. As found previously, neither small, high-density B cells nor mouse rosette+ B cells responded well to PWM. Direct interaction with allospecific T cells induces differentiation of a broader spectrum of B cells than soluble growth and differentiation factors in conjunction with polyclonal activators such as PWM and protein A containing staphylococci.

Adult↗
PubMed1986

Bacterial lipoteichoic acid sensitizes host cells for destruction by autologous complement.

Lipoteichoic acids (LTA) released by gram-positive bacteria can spontaneously bind to mammalian cell surfaces. In the present study, erythrocytes (E) sensitized with pneumococcal LTA (LTA-E) were used as a model system to determine if LTA could render host cells susceptible to damage by autologous complement. Complement (C)-mediated lysis of LTA-E from normal rats and normal humans occurred when these cells were incubated in their respective autologous sera in vitro. In addition, when LTA-E from a C2-deficient human and from C4-deficient guinea pigs were incubated in their autologous sera, there was significant lysis in vitro, demonstrating a role for the alternative pathway. The in vivo survival of 51Cr-labeled autologous LTA-E was also studied. Only 2.9% of autologous LTA-E remained in the circulation of normal rats after 90 min. In contrast, 31.2% of autologous LTA-E remained in the circulation of rats depleted of C3. Intravascular hemolysis accounted for the clearance of LTA-E in the normal rats, whereas liver sequestration was responsible for clearance in the C3-depleted rats. These results demonstrate that LTA can render the host's cells susceptible to damage by its own complement system, establishing this as a possible mechanism of tissue damage in natural bacterial infections.

Animals↗
PubMed1985

Activation of the alternative complement pathway by pneumococcal lipoteichoic acid.

Cell wall teichoic acids of some gram-positive bacteria are potent activators of the alternative pathway of complement. It is unclear, however, whether the other form of teichoic acid, cell membrane lipoteichoic acid (LTA), can also activate the alternative pathway. In the present study, radiolabelled pneumococcal LTA was found to bind spontaneously to sheep erythrocytes in a temperature- and time-dependent fashion. In addition, the presence of pneumococcal LTA on the erythrocyte surface was verified by the fact that they could be agglutinated by a myeloma protein (TEPC-15) specific for choline, a constituent of pneumococcal LTA. Pneumococcal LTA when fixed to the surface of erythrocytes was able to activate the alternative pathway of complement in both guinea pig serum deficient in the fourth component of complement and human serum deficient in the second component of complement, resulting in lysis of the sensitized erythrocytes. The sensitizing principle of the LTA preparation was removed before erythrocyte sensitization by immunoabsorption, using the choline-specific TEPC-15 myeloma protein. These data demonstrate that purified pneumococcal LTA will bind to sheep erythrocytes and endow them with the ability to activate the alternative pathway.

Animals↗
PubMed1981

The fixation of C3b to pneumococcal cell wall polymers as a result of activation of the alternative complement pathway.

The present study was performed in order to determine the identity of the pneumococcal cell wall polymer(s) to which C3b becomes fixed after activation of the alternative pathway. Purified pneumococcal autolysin was used to solubilize pneumococcal cell walls to which C3b had been fixed via activation of the alternative pathway. The resulting soluble cell wall polymers were then examined for the presence of C3b. Chromatographic separation of cell wall digests containing either radiolabeled teichoic acid or radiolabeled C3b demonstrated that although the elution profiles of the 2 radiolabels were similar, they were not identical. In addition, when teichoic acid-containing polymers were removed from solution by immunoabsorption with TEPC-15 myeloma, only 43 to 65% of the C3b was removed. These results demonstrate that C3b activated via the alternative pathway fixes both to teichoic acid-containing pneumococcal cell wall polymers and to other cell wall constituents and/or serum proteins bound to the cell wall.

Animals↗
PubMedDate not supplied

Dietary lipids and immune function.

Interest in the use of alternative dietary lipids to prevent or control human disease has gained scientific support from numerous studies which have uncovered beneficial effects of increased amounts of polyunsaturated fish and plant oils upon such diverse disease processes as atherosclerosis and coronary heart disease, rheumatoid arthritis, post-operative and post-traumatic recovery, and sepsis. The immunologic processes which underly these pathologic states, and the possible ways in which dietary lipids may influence immunologic function are areas of active research. This review aims to summarize the current views of understanding how immune-mediated processes and inflammatory states may be altered by the content and types of lipids in the diet.

Animals↗