Human models: Whipple's disease, coeliac disease and jejunoileal bypass.
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Biomedical subjects
Publications and source records attributed to P D Utsinger.
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A 40-year-old black man developed the primary features of Kawasaki disease, along with a pronounced distal motor and sensory neuropathy, abnormal electromyograms, and elevated creatine kinase levels. Results of the biopsy of a distal muscle showed myonecrosis, some type II grouping, immunoglobulin deposition in the sarcolemma, and disordered sarcomeric alignment with dilated T-tubules and terminal cisternae. Immunologic evaluation showed high concentrations of cryoglobulins and circulating immune complexes. It is possible that several manifestations of Kawasaki disease are mediated by immune complex deposition in vessels and tissues.
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Twenty-one patients with arthritis and dermatitis following intestinal bypass surgery were studied. The arthritis was polyarticular, remittent, and intermittent. Typically, the synovial fluid was inflammatory. The commonest inflammatory skin lesion was a vesiculopustular dermatitis. Nineteen patients and serum immmune complexes using the Raji cell technic. Seventeen patients had serum cryoproteins, primarily consisting of IgG 1, IgG 3, C3, and C4. Three patients had both Escherichia coli antigens and anti-E. coli antibody in their cryoprotein. Five patients had granular and one had linear deposits of immunoglobulin and complement at the dermoepidermal junction. Further evidence that bacterial antigens play a role in tissue injury was provided by detection of granular deposits of E. coli antigen at the dermoepidermal junctions in two patients, and at the glomerular capillary basement membrane in one patient.
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The influence of patterns of usage on the structure and function of the hands was formally tested. Three groups of female textile workers, each employed in a distinct and defined, atraumatic, repetitive, stereotyped manual task for at least 20 years, were identified in a single rural mill. Replicate data were obtained for the following measures of structure and function: range of motion, a score for the degree of radiographic degenerative changes at each hand joint, malalignment at digital joints determined radiographically, and a quantitative measure of osteophyte formation. Significant and consistent differences in the right hand when compared to the left were detected. Furthermore, highly significant task-related differences were demonstrated. These task-related differences in the structure and function of the hands were consistent with the pattern of usage. Therefore these three patterns of usage influence hand structure and function in the population studied.
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The serum of a 29-year old woman with a recent episode of disseminated gonococcal infection and a history of meningococcal meningitis and arthritis as a child was found to lack serum hemolytic complement activity. The seventh component of complement (C7) was not detected by functional or immunochemical assays, whereas other components were normal by hemolytic and immunochemical assessment. Her fresh serum lacked complement-mediated bactericidal activity against Neisseria gonorrhoeae, but the addition of fresh normal serum or purified C7 restored bactericidal activity as well as hemolytic activity. The absence of functional C7 activity could not be accounted for on the basis of an inhibitor. Opsonization and generation of chemotactic activity functioned normally. Complete absence of C7 was also found in one sibling who had the clinical syndrome of meningococcal meningitis and arthritis as a child and in this sibling's clinically well eight-year-old son. HLA histocompatibility typing of the family members did not demonstrate evidence for genetic linkage of C7 deficiency with the major histocompatibility loci. This report represents the first cases of C7 deficiency associated with infectious complications and suggests that bactericidal activity may be important in host defense against bacteremic neisseria infections.
The terms erosive or inflammatory osteoarthritis refer to an inflammatory condition of the interphalangeal joints of the hand. In this report, observations of 15 patients with erosive osteoarthritis are described. The principal clinical features are symmetrical synovitis of the interphalangeal joints of the hand, the knees, and the first carpometacarpal, interphalangeal, and metacarpophalangeal joints. The principal roentgenographic features are productive and destructive osseous changes. These changes, found particularly at the interphalangeal joints of the hand, consist of both central and peripheral articular erosions and cysts associated with adjacent osteophyte formation. Serologic abnormalities commonly found in rheumatoid arthritis are rarely encountered. In two thirds of the patients, the synovial fluid is noninflammatory; in the remainder, it is mildly to severely inflammatory. The injection of intra-articular corticosteroids predictably results in decreased synovitis but does not seem to affect the subsequent development of erosions.
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The cross-linking of human peripheral lymphocyte surface Ig results in an early association of cyclic adenosine 3':5'-monophosphate (cAMP) and the cell surface Ig patches. Examination of the subsequent stages of cap formation reveals the continued relationship of cAMP and the clustered surface Ig. In addition, the generalized influx of calcium produced by the ionophore A-23187 disrupts human lymphocyte caps. During the process of cap dissolution cAMP is still associated with surface Ig. Therefore, it is hypothesized that the localized concentration of cyclic nucleotide and calcium ion regulates the movement of cell surface constituents by coordinating the function of the cell's contractile and structural elements.
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Clinical, radiographic and pathologic abnormalities in calcium pyrophosphate dihydrate deposition disease (CPPD) (pseudogout) are outlined in an investigation of 85 patients with definite or probable disease and available cadaveric and human surgical material. Pyrophosphate arthropathy produced distinctive roentgenographic abnormalities with were most frequent in the knee, wrist and metacarpophalangeal joints. Although the alterations superficially resembled osteoarthritis, they were frequently more severe and progressive with extensive fragmentation of bone, causing intra-articular osseous bodies. Pyrophosphate arthropathy occurred in unusual locations, such as the radiocarpal compartment of the wrist, elbow, and patellofemoral compartment of the knee. These characteristics allow the radiologist to suggest a probable diagnosis of CPPD even in the absence of articular calcification.
THE PHYTOHEMAGGLUTININ (PHA) RESPONSE OF LYMPHOCYTES FROM UNTREATED PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) WAS STUDIED USING HIGHLY PURIFIED SUBPOPULATIONS OF CELLS INVOLVED IN THE TRANSFORMATION RESPONSE: T lymphocytes, B lymphocytes, and monocytes. Cell transformation was quantitated using both tritiated thymidine ([(3)H]-TdR) incorporation into DNA and cytofluorographic determination of cellular DNA content. Dose-response curves using six concentrations of PHA and five concentrations of cells over 0-5 days revealed a decrease in [(3)H]TdR by stimulated lymphocytes from some SLE patients. This decrease in [(3)H]TdR was paralleled by a decreased percentage of cells in S, G(2), and M phases of the cell cycle. However, abnormal response occurred entirely in those SLE patients who were hypocomplementemic. The etiology of the impaired response was further examined. Lymphocyte receptors for concanavalin A were studied using cytofluorography of lymphocytes stained with fluorescein-conjugated concanavalin A. The frequency distribution of concanavalin A receptors was similar in the normocomplementemic and hypocomplementemic lupus patients and in normals. The latex phagocytic activity of lupus macrophages was similar to normals when allogeneic normal plasma was used in the culture medium. Phagocytic activity became abnormal in the presence of SLE plasma. However, there was no difference in the [(3)H]TdR response or the percentage of cells in S, G(2), and M phases when T lymphocytes from the hypocomplementemic patients were stimulated on either autologous or normal allogeneic monocyte monolayers. Likewise, normal lymphocytes incorporated similar amounts of [(3)H]TdR and had similar percentages of cells in S, G(2), and M phases whether their T lymphocytes were stimulated on autologous or SLE monocyte monolayers. Highly purified subpopulations of B and T lymphocytes were obtained by density sedimentation or Fenwal Leuko-Pak passage of lymphocyte populations. The response to PHA by lymphocytes from the hypocomplementemic lupus patients could be seen to involve at least two abnormalities. One, in reference to normal lymphocytes, SLE T lymphocytes plus monocytes had an impaired response; two, SLE B lymphocytes plus SLE T lymphocytes plus SLE monocytes had an impaired response. Two patients in the hypocomplementemic group were treated with steroids. 5 days after steroid treatment was initiated, the percentage of cells in S, G(2), and M phases and the [(3)H]TdR response of PHA-stimulated lymphocytes returned to normal. The normalization of the [(3)H]TdR response was explained both by a return of purified T cells plus monocytes, purified B cells plus monocytes, and whole lymphocyte populations to normal responsiveness. These studies suggest that a steroid-correctable defect exists in T and B lymphocytes in SLE.