Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Yersinia enterocolitica is enteropathogenic for man and rodents. Previous studies provided evidence that Y. enterocolitica invades the lymphoid follicles of the Peyer's patches (PP) of the small intestine. In this study Y. enterocolitica-induced tissue alterations of the follicle-associated epithelium (FAE) and the underlying PP tissue were analysed by scanning (SEM) and transmission electron microscopy (TEM) as well as by conventional histological examination. For this purpose, an experimental mouse infection model including orogastric infections as well as ileal loop experiments were used. A rapid and selective colonisation of the FAE after orogastric yersinia infection was observed by SEM. TEM studies confirmed that Y. enterocolitica adhered closely to the FAE including M cells and enterocytes. Histological studies and TEM revealed that Y. enterocolitica selectively invaded the PP via M cells but not via other cells of the FAE. One day after Y. enterocolitica infection the FAE was altered and small micro-abscesses comprising yersiniae expressing the major outer-membrane protein YadA were observed immediately beneath the FAE. Adjacent villi were dilated from lymphangiectasis and transmigrating polymorphonuclear leucocytes (PMNL) were found within the epithelium. At 5-7 days after infection the FAE and parts of PP were destroyed. Profound alterations of the cyto-architecture of the PP were due to the enormous recruitment of PMNL. By day 5 after infection, abscesses were found in the mesenteric lymph nodes. However, TEM studies revealed evidence that Y. enterocolitica may disseminate from the PP not only via the lymphatics but also by invasion of blood vessels. Taken together, the results of this study demonstrate that the FAE is the primary site of host-pathogen interaction in Y. enterocolitica infection and that this pathogen penetrates M cells and subsequently induces destruction of the PP.
 ...
PMID:Penetration of M cells and destruction of Peyer's patches by Yersinia enterocolitica: an ultrastructural and histological study. 860 57

Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular brush border, is a cell surface peptidase identical to the CD10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transplantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs of graft rejection, to signs of immunoactivation in transplant fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum levels of C-reactive protein. The serum NEP levels remained normal (peak level 10.3 +/- 1.8 micrograms/l on days 6-9 after Tx, initial level after Tx 7.3 +/- 1.4 micrograms/1 on day 2; mean values +/- SEM) in patients who neither showed clinical signs of rejection nor had findings of immunoactivation in FNAB samples. On the contrary, the serum NEP levels rose clearly in patients developing acute rejection verified clinically and in FNAB samples (peak value 90.4 +/- 18.7 micrograms/l on days 6-9 post-Tx; p < 0.001 compared with patients without sings of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 +/- 22.4 micrograms/l, p < 0.001). Serum NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive findings in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory function, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotransplantation associated with early phases of immunoactivation and development of acute graft rejection. Because of the limited number of patients studied, the clinical implications of these preliminary observations for kidney transplant monitoring clearly need confirmation in larger studies.
 ...
PMID:Increased serum neutral endopeptidase activity in acute renal allograft rejection. 873 78

The mechanisms of activation and termination of autoimmune responses are poorly understood. We have studied the sites and mode of activation and elimination of T cells in actively induced experimental autoimmune neuritis (EAN) and in adoptively transferred by P2-specific T cells (AT-EAN). The bromodeoxyuridine (BrdU) technique was employed to detect in situ proliferating cells in spleen and sciatic nerve. We assessed the nuclear morphology of infiltrating T cells using morphological criteria of apoptotic cell death. Apoptosis of lymphoid cells was also investigated using molecular labeling techniques. In AT-EAN, the number of BrdU positive cells in splenic germinal centers peaked at day 2 after cell transfer [554 +/- 267] (mean +/- SEM per mm2, controls 98 +/- 35), 1 day before disease onset, and declined thereafter. BrdU incorporation in spleens from animals with active EAN peaked at day 11, around disease onset, but reached lower total values (165 +/- 29 per mm2). In neither model did we observe a significant proportion of BrdU-positive T cells in the peripheral nervous system. However, T cells exhibiting morphological signs of apoptosis were detected in the sciatic nerve immediately after disease onset. The number of these cells was highest on day 7 in AT-EAN (6.6 +/- 3.2 per mm2) and on day 17 in active EAN (11.2 +/- 2.2 per mm2) corresponding to the maximum of T cell infiltration in both animal models. T cell activation occurs systematically and not just in the autoimmune lesion. Infiltrating T cells are eliminated by apoptosis in situ, terminating the inflammatory process. Further insight into these mechanisms may help to develop new therapeutic strategies for autoimmune disorders of the peripheral nervous system.
 ...
PMID:In situ demonstration of T cell activation and elimination in the peripheral nervous system during experimental autoimmune neuritis in the Lewis rat. 892 12

The objective of the present study was to evaluate the prognostic utility in determining the risk of AIDS progression in HIV-1-infected asymptomatic hemophiliacs by in vitro immunoglobulin (Ig) synthesis. With this aim, a cohort of 28 HIV-1-seropositive hemophiliacs were studied. All showed the number of CD4 lymphocytes higher than 400 positive cells/mm3. In all cases the spontaneous and pokeweed mitogen-induced in vitro production of Ig by peripheral blood lymphocytes was evaluated at the beginning of the study and the ratio stimulated/spontaneous (Stim/Spon) synthesis was calculated. At the same time, the absolute CD8+ cell count, IgA serum immunoglobulin, p24 HIV-1 antigenemia, and beta2 microglobulin were calculated. These data were monitored during the 4-year follow-up of patients and compared with the stimulated/spontaneous Ig synthesis ratio to evaluate the predictive significance on the progression of HIV infection. According to the stimulated/spontaneous Ig synthesis ratio, hemophilic patients were separated into two categories. Group I included 12 subjects with a Stim/Spon ratio higher than 2 (the lowest value of normal controls) and group II included 16 cases with a ratio lower than 2. As control, in 36 HIV-1-negative hemophiliac individuals the stimulated/spontaneous Ig ratio ranged between 2 and 42; mean +/- SEM, 12.9 +/- 1.8. At the end of the 4-year follow-up, group I patients showed a CD4 count and clinical staging consistent with those of the first evaluation; in contrast group II demonstrated a significant decrease in CD4 lymphocytes and deterioration of clinical conditions. Our results show that a low Stim/Spon Ig ratio when the CD4 lymphocyte count was still normal appears to predict the depletion of this lymphoid subset and progression to AIDS before T CD8, IgA immunoglobulin, p24 HIV-1 antigenemia, and beta2 microglobulin abnormalities. In this setting, the stimulated/spontaneous Ig ratio may represent a useful tool for clinical decisions in HIV-1-infected hemophiliacs.
 ...
PMID:Predictor of the rate of CD4 lymphocyte loss in HIV-1-seropositive asymptomatic hemophiliacs by in vitro immunoglobulin synthesis. 893 98

The mode of heterosexual transmission of human immunodeficiency virus (HIV) is not yet understood. The semen of HIV-infected men contains free virus and infected cells, and it is not known which of these is more important for sexual transmission of the virus to women. Some investigators have presented in vitro studies supporting a cellular mode of transmission of HIV and have suggested that infected lymphoid cells may act as the primary source of infection. This has become known as the "Trojan Horse" hypothesis. In vivo demonstrations of such events are lacking and are not likely to be forthcoming using human subjects. To investigate the ability of normal lymphoid cells to invade the cervicovaginal mucosa in an experimental animal, we stained C3H/He (H-2Kk) mouse peritoneal lymphoid cells with bisbenzimide, a vital fluorescent DNA-binding dye, and inoculated the cells atraumatically into the vaginas of progestin-treated, BALB/c (H-2Kd) recipient mice. Donor cells were identified in recipient tissues by their bisbenzimide-fluorescent nuclei and by fluorescein staining of the membrane antigen, H-2Kk. Donor lymphoid cells were observed in histological sections of recipient cervicovaginal mucosa and also in the iliac lymph nodes of 34 of 36 recipient mice 24 h after inoculation into the vagina. The number of donor cells in the iliac lymph nodes was 8.6 +/- 1.4 (mean +/- SEM) cells per mouse with a range of 0-35 cells per mouse. Approximately 28% of the donor lymphoid cells in recipient lymph nodes expressed CD4, which in humans is the receptor for HIV. We did not detect F4/80, a marker of mature mouse macrophages in the donor cell population, on any of the migrating cells in recipient lymph nodes. However, this negative result is equivocal, because the marker might be down-regulated after transfer or the migrating macrophages might be difficult to dissociate from the recipient lymph node tissue. These observations in mice support the suggestion that HIV-containing lymphoid cells in the semen of infected men may invade the cervicovaginal mucosa after sexual intercourse and deliver the virus to a woman's internal environment. However, both the donor cells and the recipient reproductive tract of the mice in the present study differed in significant respects from their counterparts in humans that might be involved in heterosexual HIV transmission. Further studies are needed to determine whether this possible mode of virus transmission is mainly responsible for heterosexual transmission of HIV in humans.
 ...
PMID:Migration of foreign lymphocytes from the mouse vagina into the cervicovaginal mucosa and to the iliac lymph nodes. 911 58

The overall architecture and structure of the perivascular space in the rat thymus were studied by light microscopy using silver-impregnated sections and sections stained immunohistochemically with anti-cytokeratin antibody, and by transmission and scanning electron microscopy (TEM and SEM). In silver-impregnated sections, the perivascular space was delimited by a thin sheath of delicate argyrophilic fibers from the thymic parenchyma in the cortico-medullary region and medulla. This space was continuous with the septal connective tissue, indicating that this was the connective tissue compartment rather than with the epithelial compartment of the parenchyma. In the medulla, the perivascular space widened at places, where the argyrophilic sheath was often discontinuous and the boundary between the perivascular space and parenchyma was indistinct. Lymphatics were located in the perivascular space of the corticomedullary region and sometimes in the wide perivascular space of the medulla. The presence of a thymic epithelial sheath surrounding the perivascular space was confirmed by light microscopy of anti-cytokeratin antibody immunostained sections and by TEM. SEM observations revealed three-dimensionally that the epithelial sheath lined by collagen fibrillar (i.e., argyrophilic) layer form a rather continuous tubular structure in the cortico-medullary region, while it often interrupted in the medulla. These findings indicated that the perivascular space (i.e., the connective tissue compartment) is extensively open to the parenchyma (i.e., the epithelial compartment) in some portions of the medulla, where medullary lymphocytes are probably freely exposed to blood borne substances similar to the peripheral lymphoid tissues.
 ...
PMID:Three-dimensional ultrastructure of the perivascular space in the rat thymus. 916 92

Insulin-like growth factor-I (IGF-I) is a polypeptide mitogen which is regulated by growth hormone (GH). IGF-I mediates many of the biological functions of GH, including the maintenance of lymphoid mass and functions. Since GH secretion declines with age, we asked whether changes in the availability of IGF-I might contribute to age-associated alterations in immune functions. As a first step, we examined relationships between plasma levels of IGF-I and in vitro correlates of immunity in young and elderly subjects. Heparinized plasma and lymphocytes were collected from the peripheral blood of 34 healthy young (aged 27 +/- 0.9 years, mean +/- SEM) and 41 elderly (79 +/- 1.3 years) volunteers (31 males and 44 females in total). Plasma levels of IGF-I, measured by radioimmunoassay after the removal of IGF-I-binding proteins, were reduced among elders compared to young controls (138 +/- 8.7 ng/mL vs 80.2 +/- 4.7 ng/mL, P < 0.001). The number of circulating lymphocytes did not change with age. The proliferative response ([3H]thymidine uptake into DNA) of T-cells to concanavalin A and B-cells to pokeweed mitogen were reduced among elders (P < 0.05). An increased spontaneous antitumor natural killer (NK) activity (P < 0.001) was accompanied by a higher percentage of CD16(+) NK cells among lymphocytes in older subjects (P < 0.001). The NK cell number was positively related to IGF-I levels in young volunteers but not among elders. Correlation analysis demonstrated a highly significant relationship between plasma IGF-I levels and T-cell (but not B-cell) proliferative response during aging (r = 0.492, P < 0.001). Our results imply that reduced immunocompetence may be one of the consequences of reduced IGF-I levels in human aging. Among the three types of immune cells tested, the T-cells were most sensitive to fluctuations in IGF-I levels. Reduced IGF-I availability may be one of the determinants of the decline in T-cell-mediated immune function in the elderly. To our knowledge, this is the first report presenting correlative data on concurrent changes in IGF-I levels and immune parameters in human aging.
 ...
PMID:Relationship between plasma IGF-I levels, in vitro correlates of immunity, and human senescence. 974 13

The authors examined the pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in 17 patients (4 children, 13 adults) with B-lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5 patients with non-Hodgkin's lymphoma (NHL). The immunoconjugate was administered intravenously as a 1-hour continuous infusion at a dose level of either 0.1 mg/kg (N = 12) or 0.18 mg/kg (N = 5), and the plasma concentration-time data were modeled by using the WinNonlin program to estimate the pharmacokinetic parameters. Pharmacokinetic analyses revealed a plasma half-life of 19 +/- 4 hours, mean residence time of 22 +/- 4 hours, and a systemic clearance of 18 +/- 2 mL/h/kg. The average (mean +/- SEM) values for the maximum plasma concentration Cmax, volume of distribution at steady state (Vss), and area under curve (AUC) were 1092 +/- 225 ng/ml, 291 +/- 37 mL/kg, and 9987 +/- 2021 micrograms x h/L, respectively. The AUC values were higher at the 0.18 mg/kg dose level than at the 0.1 mg/kg dose level (16,848 +/- 5118 micrograms x h/L vs. 7128 +/- 1156 micrograms x h/L, p = 0.009). Patients with ALL had a significantly larger volume of distribution at steady state (332 +/- 47 mL/kg vs. 191 +/- 12 mL/kg, p = 0.04), faster clearance (21 +/- 3 mL/h/kg vs. 11 +/- 2 mL/h/kg, p = 0.03), and lower dose-corrected AUC than patients with NHL (6010 +/- 836 micrograms x h/L vs. 12,044 +/- 2707 micrograms x h/L, p = 0.006). There was a trend toward faster clearance rates (23 +/- 4 mL/h/kg vs. 16 +/- 3 mL/h/kg, p = 0.1), shorter elimination half-lives (5.7 +/- 3.6 hours vs. 13 +/- 8.8 hours, p = 0.1), and shorter mean residence times (11 +/- 3 hours vs. 25 +/- 5 hours, p = 0.08) for non-Caucasian patients as compared to Caucasian patients. When compared to adult patients, pediatric patients showed a significantly larger volume of distribution at steady state (418 +/- 82 mL/kg vs. 252 +/- 34 mL/kg, p = 0.02) and a longer elimination half-lives (18.4 +/- 13.6 hours vs. 8.7 +/- 6.7 hours, p = 0.04). The pharmacokinetics of B43-Genistein was not affected by the gender of the patients or by bone marrow transplantation in past medical history. Overall, B43-Genistein showed favorable pharmacokinetics in this heavily pretreated leukemia/lymphoma patient population, which is reminiscent of its recently reported favorable pharmacokinetics in cynomolgus monkeys. To our knowledge, this is the first clinical pharmacokinetics study of a tyrosine kinase inhibitor containing immunoconjugate.
 ...
PMID:Clinical pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in patients with B-lineage lymphoid malignancies. 1058 90

A recombinant immunotoxin was constructed from the hybridoma antibody TH-69 directed against human CD7, a surface antigen of leukemic T cells. The antibody was subcloned as a single chain Fv (scFv) fragment and genetically linked to a truncated Pseudomonas exotoxin A fragment containing the catalytic domains II and III but lacking the receptor binding domain I. Domain I was replaced by the scFv, thus conferring restricted specificity for CD7-positive cells. The bacterially expressed and purified toxin retained binding specificity for CD7-positive cells. It promoted apoptosis in two CD7-positive cell lines derived from T-lineage acute lymphoblastic leukemias, CEM and Jurkat, but not in the CD7-negative B-lymphoid lines REH, Nalm-6, and SEM. Maximum killing in excess of 95% was reached after 96 h in CEM and Jurkat cells with a single dose of 100 ng/ml. Cells treated with a similarly constructed scFv-exotoxin A immunotoxin against melanoma-associated chondroitin sulfate proteoglycan, an antigen absent from leukemic T cells, remained unaffected. Lysis of target cells occurred via apoptosis as evidenced by staining with Annexin V and specific cleavage of poly(ADP-ribose) polymerase. Approximately 20% of leukemic cells from a patient with CD7-positive acute T-cell leukemia kept in long-term primary culture for 30 cell generations were killed within 96 h after treatment with the toxin. These findings justify further evaluation of the agent in view of potential therapeutic applications.
 ...
PMID:A recombinant CD7-specific single-chain immunotoxin is a potent inducer of apoptosis in acute leukemic T cells. 1201 63

We evaluated the expression of T cell-restricted intracellular antigen (Tia-1), granzyme B, and perforin by lymphocytes and the degree of epithelial apoptosis in oral and cutaneous lichen planus (LP) in 51 untreated cases, including 27 oral LP (OLP) and 24 cutaneous LP (CLP) cases. The number of total dermal-positive lymphocytes in OLP and CLP was similar, indicating similar activity of the inflammatory process. Intraepithelial Tia-1-positive, perforin-positive, and granzyme B-positive lymphoid cells were more numerous in OLP than in CLP (P < .05). The epithelial cell apoptotic index (AI) was increased significantly in OLP (P < .05), particularly in erosive-atrophic variants. A linear correlation between AI and the mean +/- SEM number of intraepithelial and dermal perforin+ cells (6.85 +/- 2.44 and 27.48 +/- 10.19, respectively), per 10 high-power fields for OLP and for CLP (1.17 +/- 0.88 and 10.42 +/- 5.74, respectively), was found (intraepithelial, r = 0.50; dermal, r = 0.51; P < .01). These data suggest a pivotal role for perforin in triggering epithelial cell apoptosis. The differences of infiltrating cytotoxic cells and related AI observed in OLP and CLP are in keeping with the clinical behaviors that distinguish these LP variants.
 ...
PMID:Cytotoxic molecule expression and epithelial cell apoptosis in oral and cutaneous lichen planus. 1515 Dec 17


<< Previous 1 2 3 4 5 Next >>