RT-PCR with affinity-captured mRNA.
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Humans↗
Biomedical subjects
J S Jaffe
Publications and source records attributed to J S Jaffe.
NIH conference. New insights into common variable immunodeficiency.
Common variable immunodeficiency (CVI) is a heterogenous immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, and various immunologic abnormalities. In addition to recurrent infections, patients with this syndrome also have an increased incidence of autoimmune disease and malignancy. Because the spectrum of associated diseases is broad, patients with CVI are seen by various medical specialists. This review discusses the pathogenesis, clinical manifestations, diagnosis, and treatment of CVI.
B-Lymphocytes↗
Reduced interleukin-2 (IL-2) production in common variable immunodeficiency is due to a primary abnormality of CD4+ T cell differentiation.
Common variable immunodeficiency (CVI) is a condition characterized by hypogammaglobulinemia and impaired antibody responses, resulting in recurrent bacterial infections in untreated patients. In addition, affected individuals exhibit an increased incidence of autoimmunity, malignancy, and certain viral infections, suggesting the presence of an underlying generalized immune dysregulation. We have previously described a subgroup of CVI patients in whom T cells within PBMC populations exhibit a selective defect in lymphokine production. IL-2, IL-4, and IL-5 mRNA production was impaired in these patients, while proliferation, IL-2R expression, and c-myc mRNA production were normal. In the present series of experiments, using highly purified CD4+ T cells prepared by negative selection, we show that this lymphokine production defect is a primary abnormality of CVI CD4+ T cells: whereas CD4+ T cells from CVI patients proliferate normally in response to stimulation by PHA, staphylococcal enterotoxin B (SEB), or anti-CD2 antibodies, these stimuli induce significantly less IL-2 production than observed with CD4+ T cells from normal individuals. Furthermore, we show that this IL-2 production defect is not due to an accessory cell abnormality, since it was seen in the presence of normal (allogeneic) accessory cells, and patient accessory cells supported normal amounts of IL-2 production by PHA-stimulated CD4+ T cells obtained from normal individuals. Of interest, we also found that while IL-2 production by CD4+ T cells from CVI patients induced by stimulation with immobilized anti-CD3 antibody was reduced compared to CD4+ T cells from normal control individuals, this reduction was not statistically significant. Furthermore, stimulation of both CVI patient and normal CD4+ T cells with either ionomycin+phorbol myristate acetate or a combination of immobilized anti-CD3 antibody plus anti-CD28 antibody resulted in a 50-fold increase in IL-2 production compared to stimulation with immobilized anti-CD3 antibody alone, and, under these conditions, CVI and normal CD4+ T cells produced equivalent amounts of IL-2. Finally, minor defects in interferon-gamma production by CD4+ T cells from CVI donors were observed, but these were less severe than the IL-2 production defects and were not statistically significant. We conclude that a primary abnormality of lymphokine production exists in the CD4+ T cells of a subset of patients with CVI.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibodies, Monoclonal↗
T-cell abnormalities in common variable immunodeficiency.
Common variable immunodeficiency (CVI) is a heterogeneous condition marked by a number of different immunologic defects. One group of patients, perhaps 60% of the CVI group as a whole, is characterized by T cells that produce reduced amounts of IL-2 (mRNA and protein product), IL-4, and IL-5 (mRNA) when stimulated with phytohemagglutinin. This defect does not extend to all lymphokines, however, because the cells produce normal amounts of interferon-gamma (mRNA and protein product) when exogenous IL-2 is present. Recently, we have reexamined the T cell lymphokine production defect using a panoply of T-cell activation stimuli and have shown that the defect is a subtle one that depends on activation of the cell via the CD3-T-cell receptor complex. Because T cells proliferate normally when stimulated via this receptor, this finding suggests the presence of a "downstream" defect, perhaps one involving the factors that are necessary for activation of lymphokine genes. A second form of CVI, in this case involving approximately 30% of the CVI group as a whole, is characterized by a reduced CD4/CD8 ratio and elevated numbers of CD8+ T cells bearing the CD57 marker. Although the CD4+ T cells in this patient group elaborate normal amounts of IL-2 under various activation conditions, their CD8+ T cells produce increased amounts of interferon-gamma. Furthermore, the CD8+ T cells in this case act as "suppressor" T cells, which suppress IgG production but not IgM production of purified (normal) SAC+, IL-2-induced B cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, CD↗
Cytokines and their role in the pathogenesis of severe food hypersensitivity reactions.
Cytokines are proteins produced by one cell that are capable of altering the behavior of another cell. Their biologic effects are both pleomorphic and redundant. A number of cytokines have been implicated in the genesis of allergic reactions, including IL-4, IL-5, IL-6, and tumor necrosis factor (TNF). In contrast, other cytokines such as gamma interferon (gamma-IFN) may have biologic actions that act to limit allergic responses. In studies on patients with severe food allergy, we have found cytokine production from peripheral T cells to be abnormal following mitogenic stimulation. These lymphokine abnormalities may contribute to the elevation in IgE and the eosinophilia seen in severe food allergy.
Cytokines↗
Carcinoma of prostate in men aged fifty and under: therapeutic options.
We made a retrospective study of 20 men, aged fifty or under, with adenocarcinoma of the prostate to evaluate presenting symptoms, stage, grade, and therapeutic results. Sixty-five percent were found to have extracapsular spread of disease (Stage C or D). The therapy used was one or a combination of three types: radical prostatectomy, radiation therapy, and hormonal manipulation. Five of 6 patients with Stage B disease and 3 of 6 patients with Stage C disease were treated with radiation therapy. The other Stages B and C patients underwent radical prostatectomy. In all 5 of Stage B patients receiving radiation, therapy failed; the mean time to tumor recurrence was 3.2 years. Two of 3 patients with Stage C disease died of metastatic disease within three years of receiving radiation. The 4 patients (Stages B and C) who underwent radical prostatectomy are free of disease. There was a statistically higher failure rate among the radiation therapy patients with Stages B and C disease than among the surgical patients (X2 = 8.4, p less than 0.1).
Adenocarcinoma↗
A novel lymphoproliferative/autoimmune syndrome resembling murine lpr/gld disease.
In mice, the two distinct autosomal recessive genes lpr and gld can induce a syndrome characterized by autoantibody formation and the progressive accumulation of an unusual CD4-CD8- T cell population in peripheral lymphoid tissue. This phenotype does not precisely mirror any human disease. In this report we describe two patients with a progressive lymphoproliferative disorder associated with autoimmunity. The peripheral blood and lymph nodes of these patients contained large numbers of an unusual CD4-CD8- T cell population. These CD4-CD8- T cells express surface markers characteristic of mature peripheral blood T cells (CD3, CD2, CD5), express the alpha/beta form of the T cell receptor, and do not express surface markers characteristic of immature thymocytes (CD1) or NK cells (CD16, CD56). Functionally, these cells exhibited deficient proliferation and lymphokine production upon stimulation with mitogenic antibodies to CD3 or CD2. Both proliferation and lymphokine production could be augmented by co-stimulation with an antibody directed at the CD28 determinant. The clinical and immunological features of this syndrome resemble the lymphoproliferative/autoimmune disease seen in lpr and gld mice.
Animals↗
3-dimensional sonographic analysis based on color flow Doppler and gray scale image data: a preliminary report.
This paper presents preliminary results of a technique that permits acquisition and display of three-dimensional (3D) anatomy using data collected from color flow Doppler and gray scale image sonography. 3D sonographic image data were acquired as two-dimensional planar images with commercially available equipment. A translational stage permitted the transducer position and orientation to be determined. Color flow sonographic video image data were digitized into a PC-AT computer along with transducer position and orientation information. Color flow velocity and gray scale data were separated, 3D filtered, and thresholded. A surface rendering program was used to define the vessel blood-lumen interface. Planar slices of arbitrary orientation and volume rendered images were displayed interactively on a graphics workstation. The technique was demonstrated in a lamb kidney in vitro and for the carotid artery at the bifurcation in vivo. Our results demonstrate the potential of 3D sonography as a technique for visualization of anatomy. Color flow data offer direct access to the vascular system, facilitating 3D analysis and display. 3D sonography offers potential advantages over existing diagnostic studies in that it is noninvasive, requires no intravenous contrast material, offers arbitrary plane extraction and review after the patient has completed the examination, and permits vascular anatomy to be visualized clearly via rendered images.
Animals↗
Difference Fourier analysis of "surface features" of bacteriorhodopsin using glucose-embedded and frozen-hydrated purple membrane.
A difference Fourier map of the projected structure of bacteriorhodopsin has been synthesized from electron diffraction amplitudes collected from membranes prepared in the glucose-embedded state and the frozen-hydrated state. Phases of a recently published data set for glucose-embedded specimens were used for the difference Fourier map. Moderate resolution (9 A) and high resolution (4.25 A) maps both indicate that glucose is exchangeable for water in the region of the map corresponding to the lipid regions. We interpret this as indicating that there is a small surface depression in this region of the structure. The depth of this feature is estimated to be 1/6 the thickness of the protein region in the membrane. The data obtained in this study rules out the existence of an aqueous transmembrane channel, the dimensions of which are large enough to allow free exchange of glucose for water. Several new features are also observed in the protein region of the membrane. These features are probably due to segments of the polypeptide at the aqueous interface that are well ordered in frozen-hydrated specimens but not in glucose-embedded specimens. Candidate structures for the origin of these features are extensions of the helices, or linker regions connecting the helices.
Bacteriorhodopsins↗
Preparation of frozen-hydrated specimens for high resolution electron microscopy.
A method is presented for preserving the high resolution structure of biological membranes in a frozen-hydrated environment for electron microscopy. The technique consists of sandwiching a specimen between two carbon films and then waiting while some of the solvent evaporates. When the solvent layer is judged to be of an appropriate thickness, the specimen is then frozen in liquid nitrogen. The specimen can then be inserted into the precooled stage of an electron microscope. Electron diffraction studies of the purple membrane of Halobacterium halobium recorded at -120 degrees C have shown that the structure can be preserved to a resolution of 3.5 A. The main advantage of this method over previous techniques is that the hydrating conditions can be accurately controlled.
Freeze Drying↗
Bilateral amyloidosis of the ureter associated with carcinoma.
We report a case of coexisting amyloid and neoplasm in a localized ureteral lesion. This case also represents the third reported instance of sequential bilateral ureteral amyloidosis. Right nephroureterectomy revealed amyloid and an in situ focus of low grade transitional cell carcinoma. Three years later amyloid in the distal left ureter was resected and the gap was bridged by a bladder hitch and Boari flap. Subsequent followup has been uneventful.
Amyloidosis↗
Beneficial actions of nalorphine during hemorrhagic shock in cats.
Endogenous opiates have been reported to have detrimental effects on the circulatory system during hemorrhagic shock. However, the specific opiate receptor subtype which mediates these actions has not been defined. In the present study, we have utilized the mixed agonist/antagonist, nalorphine (N-allylnormorphine), which exhibits kappa (kappa) and sigma (sigma) receptor agonism as well as mu (mu) receptor antagonism, to investigate the role of the mu receptor in hemorrhagic shock. Nalorphine (2 mg/kg) produced no significant changes in any observed experimental variable in sham-shocked animals. Shocked animals treated with nalorphine (2 mg/kg) maintained significantly higher final mean arterial blood pressures (MABP) than animals which received only vehicle (102 +/- 3.8 vs 61 +/- 6.6 mm Hg, respectively, p less than 0.001). In addition, nalorphine significantly reduced the rise in plasma MDF activity observed in untreated hemorrhaged animals (42 +/- 3.0 vs 59 +/- 4 U/ml, p less than 0.02). Our results support a significant role for the mu receptor in the deleterious actions of endogenous opioids during hemorrhagic shock.
Animals↗
Low frequency sounds from sustained contraction of human skeletal muscle.
Low frequency audible vibrations are produced by human skeletal muscles undergoing sustained contraction. The effect is easily demonstrable with an electronic stethoscope which amplifies sound below 50 Hz. Autocorrelation analysis of the signal shows that it is periodic with a frequency 25 +/- 2.5 Hz. The quality of the sound is the same for all the skeletal muscles tested and is unaffected by changes in tension, ambient temperature, and blood flow. Electrically-stimulated contraction produces a sound which is indistinguishable from voluntary contraction. The amplitude of the sound increases linearly with tension. The sound signals are uncorrelated both in frequency and phase with electromyographic signals obtained simultaneously while the muscle is contacted. Arguments are presented to show that the sounds may be an intrinsic property of muscle contraction.
Humans↗
Ureteral segment replacement using a circumferential small-intestinal submucosa xenogenic graft.
We wished to determine whether small-intestinal submucosa (SIS) will epithelialize when used as a ureteral replacement material. An 11-mm segment of native ureter was excised from eight New Zealand White rabbits and replaced with an 11-mm porcine SIS graft, which was circumferentially wrapped around a ureteral stent. The SIS ureteral grafts were harvested at 11 days or 35 days postimplantation and examined grossly and by standard light microscopy techniques. Partial epithelialization with the ingrowth of urothelium, smooth muscle cells, and blood vessels was observed in the grafts harvested at 11 days postimplantation. The SIS ureteral grafts examined at 35 days postimplantation showed additional restructuring of the smooth muscle cell layer and more organized epithelialization in comparison to the SIS graft examined at 11 days. After 35 days of regenerative healing, elements of all three layers of the native ureter were observed within the collagen matrix of the SIS graft. No significant complications were observed, but all subjects (8/8) demonstrated mild intra-abdominal adhesions. Mild collecting system dilatations were observed in 4/4 (100%) of the animals harvested at 35 days and in 0/4 (0%) of the animals harvested at 11 days. We have this demonstrated in this preliminary study that SIS xenografts will epithelialize when used as a ureteral replacement material. The repair mechanism of these ureteral grafts occurred through a regenerative healing process rather than by scar formation. With further studies, this material may prove to be a useful treatment option in patients with ureteral injuries.
Animals↗
An alternative to synthetic aortic grafts using jejunum.
Synthetic materials currently used for arterial grafts can provoke serious complications such as infection, rejection, and incomplete reendothelialization. Porcine small intestinal submucosa (SIS) allografts (homografts) may not share these disadvantages yet still may provide an effective graft alternative. This study was designed to provide additional information concerning the performance of this material when used as an allo-patch graft. A porcine model was selected to enable hemodynamic comparisons to the adult human physiology. Slaughterhouse small intestine was used to prepare the SIS graft material. A well-vascularized section ofjejunum was resected, rinsed, and maintained in 0.9% NaCl solution containing 10% gentamicin. The graft was prepared by removing the serosal layer, inverting the material, and discarding the mucosal surface in a similar manner. The remaining submucosa and stratum compactum constituted the graft material and was subdivided into sizes from 1.5 to 3.0 cm2 tacked to foil for manageability, and was returned to the gentamicin solution. The surgery was initiated with a femoral arterial line in the anesthetized swine, followed by isolation and preparation of the infrarenal aorta for grafting. Cross-clamps were applied and a 1.0 x 1.5-cm section of aortic wall was resected. Two sides of allograft were freed from the foil and sewn into the aorta. Then the remaining sides were removed from the foil and final graft placement was completed. The graft was harvested at postoperative day 28 and presented for microscopic examination. Results confirmed that reendothelialization with neovascularization had occurred during this interval.
Animals↗