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Biomedical subjects

T J Watson

Publications and source records attributed to T J Watson.

16 recordsLinked to original sources
PubMed1999

Possible extrathymic development of nonfunctional T cells in a patient with complete DiGeorge syndrome.

Complete DiGeorge syndrome is characterized by the clinical triad of cardiac malformation, hypocalcemia, and T cell immunodeficiency due to congenital athymia. We describe an infant with complete DiGeorge syndrome who at presentation had no circulating T cells detectable by flow cytometry. The patient spontaneously developed circulating T cells but these cells did not proliferate in response to mitogens. The T cell receptor Vbeta repertoire was severely restricted. All T cells were host, not maternal, as assessed by fluorescent in situ hybridization evaluation of 22q11 hemizygosity. At autopsy, this patient had no grossly detectable thymus tissue and no microscopic evidence for thymopoiesis. These findings suggest that appearance of T cells in infants with complete DiGeorge syndrome may represent oligoclonal expansions of a small number of T cells that may have matured extrathymically and which do not respond in vitro to mitogen stimulation.

B-Lymphocytes↗
PubMed1998

Esophageal replacement for end-stage benign esophageal disease.

BACKGROUND: Benign esophageal diseases constitute a common group of disorders that are generally managed with medical therapy or surgery designed to improve foregut function. A small subset of patients, however, has advanced disease that requires esophageal replacement to achieve symptomatic relief. PATIENTS AND METHODS: One hundred four patients with benign esophageal disease who underwent esophageal reconstruction over a 21-year period (1975 to 1996) were reviewed retrospectively. Dysphagia was the major symptom driving surgery in 80% of the patients. Colon was used to reconstruct the esophagus in 85 patients; stomach, in 10 patients; and jejunum, in 9 patients. Forty-two patients who had lived with their reconstruction for 1 year or more answered a postoperative questionnaire concerning their long-term functional outcome. RESULTS: In the 104 patients, the primary underlying abnormality leading to esophageal replacement was end-stage gastroesophageal reflux (37 patients), an advanced motility disorder (37 patients), traumatic, iatrogenic or spontaneous perforation (15 patients), corrosive injury (8 patients), congenital abnormality (6 patients), or extensive leiomyoma (1 patient). Ninety-eight percent of patients reported that the operation had cured or improved the symptom driving surgery. Ninety-three percent were satisfied with the outcome of the operation. The overall hospital mortality rate was 2%, and the median hospital stay was 17 days. Graft necrosis occurred in 3% of patients, and anastomotic leak occurred in 6% of patients (or 2% of the total number of anastomoses). CONCLUSIONS: Esophageal replacement for benign disease can be accomplished with a low mortality rate and a marked improvement in alimentation. Reconstruction restores the pleasure of eating and is viewed by the patient to be highly successful.

Adolescent↗
PubMed1997

Successful formation of a chimeric human thymus allograft following transplantation of cultured postnatal human thymus.

Transplantation of cultured postnatal human thymus was performed in a patient with complete DiGeorge syndrome. Biopsy of the graft 3 mo after implantation revealed normal CD1+ thymocytes in thymic cortical epithelial regions and CD1- thymocytes in thymic medullary epithelial regions, respectively. HLA analysis of graft thymocyte and thymic microenvironment components demonstrated that developing thymocytes and thymic macrophages were recipient derived, while thymic epithelial components were of donor origin. The patient, who initially had no T cells and had profoundly defective T cell function, developed normal T cell responses to mitogens and Ags, tolerance to donor in a mixed lymphocyte reaction, and normal Ab titers after tetanus toxoid and pneumovax immunization. Thus, transplantation of cultured postnatal human thymic tissue in humans can form functional chimeric thymic tissue, and may provide a strategy to reconstitute the peripheral T cell pool in select congenital and acquired immune deficiency syndromes.

Chimera↗
PubMed1997

Mutations in purine nucleoside phosphorylase deficiency.

Purine nucleoside phosphorylase deficiency is an inherited disease of purine metabolism characterized clinically as combined immunodeficiency. The molecular defects have been published for 4 different alleles in 3 patients. We report four new mutations including two amino acid substitutions, A174P and G190V, a single codon deletion, delta I129, and a point mutation in intron 3 which leads to aberrant splicing and creation of a premature stop codon in exon 4 (286-18G-->A). Of the previously reported mutations, E89K was found in one additional patient, and R234P was found in 3 unrelated patients, making R234P the most common mutation reported to date in this disease.

Alleles↗
PubMed1997

The human thymic microenvironment during organ culture.

Cultured human thymic tissue has been transplanted into many patients with T cell dysfunction; however, little is known about the effect of in vitro culture on thymic tissue. Human postnatal thymic organ cultures were established in vitro to study the growth potential of the thymic epithelium and the expression of intracellular and surface antigens with time in culture. Marked depletion of bone marrow-derived cells was observed within 3 weeks of initiation of organ cultures although some viable CD3+ cells could still be detected. Thymic epithelial cells in in vitro explants continued to express MHC class I and class II antigens as well as cytokeratins. Thymic epithelial cells within cultured thymic organ slices maintained their postnatal growth potential, in that cytokeratin-positive epithelial monolayers could be established in vitro from these thymic slices up to 12 weeks after initiation of organ culture. Thus, thymic explants remained viable in culture and could potentially be used to reconstitute immunity in T cell deficient patients.

Antibodies, Monoclonal↗
PubMed1997

Esophageal replacement for end-stage benign esophageal disease.

The fact that esophageal resection and foregut reconstruction for benign disease can be performed with only a 2% mortality and minimal morbidity is encouraging news to patients who are crippled by the various manifestations of end-stage disease. The continuation of slow, anxious, and socially restricted alimentation or the maintenance of nutrition by enteral or parenteral means is unnecessary. The patient should be referred to a unit skilled in evaluating foregut function, performing esophageal replacement surgery, and caring for patients in the perioperative period. In our experience, the colon, when available, is the preferred conduit for esophageal replacement over the long term. Even though some subtle preoperative symptoms of foregut dysfunction may persist after surgery, the overall outcome is generally judged to be satisfactory. Indeed, patients can re-enter society and live a normal and fulfilled life after remedial surgery. Prolonged attempts at medical management of patients with severe derangements of esophageal structure and function are not warranted. Long-term esophageal replacement for severe end-stage benign disease can be accomplished with low mortality, a high degree of success, and a marked improvement in the quality of alimentation. Reconstruction restores the pleasure of eating and is viewed by the patient to be highly successful.

Colon↗
PubMed1997

Normalization of the peripheral blood T cell receptor V beta repertoire after cultured postnatal human thymic transplantation in DiGeorge syndrome.

Complete DiGeorge syndrome is an immunodeficiency disease characterized by thymic aplasia and the absence of functioning peripheral T cells. A patient with this syndrome was transplanted with cultured postnatal human thymic tissue. Within 5 weeks of transplantation, flow cytometry, T cell receptor V beta sequence analysis, and cell function studies showed the presence of oligoclonal populations of nonfunctional clonally expanded peripheral T cells that were derived from pretransplantation T cells present in the skin. However, at 3 months posttransplantation, a biopsy of the transplanted thymus showed normal intrathymic T cell maturation of host T cells with normal TCR V beta expression on thymocytes. By 9 months postransplantation, peripheral T cell function was restored and the TCR V beta repertoire became polyclonal, coincident with the appearance of normal T cell function. These data suggest that the transplanted thymus was responsible for the establishment of a new T cell repertoire via thymopoiesis in the chimeric thymic graft.

Base Sequence↗
PubMed1996

Mapping cross-linking sites in modified proteins with mass spectrometry: an application to cross-linked hemoglobins.

The combined use of trypsin digestion and peptide mass mapping by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is reported here as an effective and rapid means for identifying the cross-linking sites in human oxy hemoglobin A (HbA) cross-linked with either bis(3,5-dibromosalicyl)-succinate or -glutarate. MALDI-MS analysis of a nondigested sample of oxy HbA modified with bis(3,5-dibromosalicyl)-glutarate showed that cross-linking only occurred between the beta 1- and beta 2-protomers and not between alpha 1- and alpha 2- or alpha- and beta-protomers, along with a modification reaction on an un-cross-linked beta-chain. Results of the MALDI tryptic peptide mass maps of cross-linked hemoglobins showed several cross-linked peptides having masses consistent with: beta Val67-Lys95-XL-beta Val67-Lys95, beta Val67-Lys95-XL-beta Val67-Arg104, beta Val67-Arg104-XL-beta Val67-Arg104, where XL represents the succinyl or glutaryl bridging span moiety. Each of these peptides contains Lys82, the targeted residue for these reagents, substantiating the cross-linking sites at beta 1Lys82-beta 2Lys82. This approach in general will enable rapid identification of the cross-linking sites in engineered proteins or intracellularly recombinant cross-linked proteins when the mass of the cross-linker and the protein primary structure are known.

Amino Acid Sequence↗
PubMed1996

Pediatric lobar lung transplantation.

The disparity between available donors and potential recipients of lung transplants has demanded a certain degree of flexibility on the part of transplantation surgeons. Marginal donors are now being used more frequently, and downsizing lungs from larger donors to fit into small recipients is quite common. In some instances, particularly in the circumstances of children, a single lobe from a much larger donor may serve very well as an entire lung in the recipient. Although either the upper or lower lobes from either side may be used, the lower lobes, especially the left, are better suited for this purpose because of the anatomy of the arterial, venous, and bronchial systems. As an extension of this concept, living-donor lung transplantation is now an accepted practice in carefully selected patients. Most children are best treated with bilateral lobar transplantation, particularly when cystic fibrosis is the indication. For living-donor transplantation, this obviously involves engaging two willing donors able to pass a rigorous physical and psychological evaluation. Although the recipients are generally sicker than the average cadaveric lung transplant recipient, early results to date have been similar to those receiving cadaveric lungs. In this article, we will describe our experience with this procedure, including the evaluation process, the technical aspects of the donor and recipient operations, and the results in the donors and recipients.

Adolescent↗
PubMed1988

Next-of-kin attitudes regarding participation in an epidemiologic case-control study.

We assessed next-of-kin's attitudes about participating in an epidemiologic case-control study of adult acute nonlymphocytic leukemia. Responses from a mailed questionnaire indicated that 95 per cent were glad they participated. While 74 per cent benefited, 18.5 per cent were bothered in some way. Results concerning the need to obtain physician permission before contacting next-of-kin were inconclusive; however, 8 of 10 females contacted by the case's physician considered consent necessary.

Adult↗
PubMed1987

Fc-mediated endocytosis by human neutrophils. Ultrastructural studies.

Fc Receptors (FcR) mediate the binding and uptake by polymorphonuclear leukocytes (PMN) of antibody-coated particles and soluble immune complexes. We have studied Fc-mediated endocytosis by PMN ultrastructurally using a gold-conjugated monoclonal antibody (3G8) to block or to mark the location of FcR. Phagocytosis of antibody-coated erythrocytes (EIgG) was initiated rapidly after binding to discrete foci on the PMN plasma membrane. After the phagocytosis of EIgG, we examined the distribution of FcR remaining on the PMN plasma membrane. 3G8-Colloidal gold continued to bind to PMN after ingestion of up to three EIgG, demonstrating that all PMN FcR are not utilized during a brief phagocytic event. The endocytosis of soluble immune complexes was examined by labeling plasma membrane-bound rabbit immune complexes with goat anti-rabbit IgG conjugated to colloidal gold. Gold was found in clusters randomly distributed over the plasma membrane at 4 degrees C. When cells were warmed to 37 degrees C, numerous endocytic vesicles were observed as early as 2.5 minutes after warming. After 30 minutes at 37 degrees C, large vesicles, 1 micron in diameter, were found to contain 20 to 30 gold particles. The endocytosis of 3G8 was also examined using colloidal gold. After binding of 3G8-gold at 4 degrees C, clusters of large vesicles, up to 2 micron in diameter, were rapidly formed at 37 degrees C.

Animals↗
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