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Biomedical subjects

E S Mingioli

Publications and source records attributed to E S Mingioli.

11 recordsLinked to original sources
PubMed1991

Changes in leukocyte recirculation, NK cell activity, and HLA-DR expression in peripheral blood mononuclear cells of MS patients treated with Poly ICLC.

To investigate the cellular immune effects of the interferon inducer, Poly ICLC, in humans, peripheral blood mononuclear cells from patients with multiple sclerosis receiving Poly ICLC as part of a preliminary clinical trial were studied. Peripheral blood mononuclear cell phenotype analysis using fluoresceinated monoclonal antibodies and flow microfluorometry showed decreases in the percentages and absolute numbers of all lymphocyte subsets 24 h after infusion. These changes returned toward baseline at 48 h except the percentage of CD-4 positive cell which increased above baseline levels. The percentage of HLA-DR antigen positive cells and CD-16 (Leu 11a) positive cells were increased 24 h after infusion but returned to baseline at 48 h. NK activity as determined by chromium release from K562 target cells was decreased at 24 h but increased 48 h after drug infusion. The increases in percentages of HLA-DR antigen and CD-16 positive cells at 24 h and NK activity at 48 h are consistent with the in vitro effects of IFN while the decreases in peripheral blood mononuclear cells are suggestive of changes in cell recirculation.

Antigens, CD↗
PubMed1988

Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis.

Tropical spastic paraparesis (TSP) is a slowly progressive myelopathy associated with increased serum and cerebrospinal fluid antibodies to the human T-lymphotropic retrovirus type I (HTLV-I) (ref. 1), and has been observed in many regions of the world. A similar condition known as HTLV-I-associated myelopathy occurs in the Kagoshima prefecture of Japan. Recent but controversial reports suggest involvement of virus related to HTLV-I in multiple sclerosis. Magnetic resonance imaging and electrophysiological studies indicate that TSP lesions are like multiple sclerosis in that they are disseminated throughout the nervous system. Complete virus from patients with TSP has proved difficult to isolate using techniques successful in adult T-cell leukaemia cases associated with HTLV-I. Here we report the isolation of an HTLV-I-like virus from T-cell lines derived from the peripheral blood and cerebrospinal fluid of TSP patients. The monoclonal antibody OKT3 was used to generate non-transformed T-cell lines that express HTLV-I antigens. Infectious virus was demonstrated by co-cultivation and complete, replicating virions were visualized ultrastructurally.

Antigens, Viral↗
PubMed1988

Humoral and cellular immune responses to matrix protein of measles virus in subacute sclerosing panencephalitis.

The immune response to matrix (M) protein of measles virus was examined in patients with subacute sclerosing panencephalitis (SSPE) and controls. Antibodies specific for M and nucleocapsid (NC) proteins in 11 serum and 8 cerebrospinal fluid (CSF) samples from patients with SSPE were quantitated by enzyme-linked immunosorbent assay by using affinity-purified measles virus proteins. Geometric mean anti-NC antibody titers were higher in the serum (6.58 +/- 0.98 [mean +/- standard deviation]) and CSF (4.38 +/- 0.74) of SSPE patients compared with controls. Anti-M antibodies were present in the serum and CSF of all SSPE samples tested but in titers lower than those of anti-NC antibodies. Geometric mean anti-M antibody titer was 3.35 +/- 0.53 in sera from patients with SSPE compared with 3.05 +/- 0.66 in sera from patients with other neurological diseases and 3.12 +/- 0.74 in sera from healthy individuals. Geometric mean anti-M antibody titer was 2.59 +/- 0.86 in the CSF of eight patients with SSPE compared with a mean less than 1.00 for patients with other neurological disease (controls). Intrathecal synthesis of anti-M or anti-NC antibodies was established in four patients with SSPE. The cellular immune responses to M, F, HA, and NC proteins were examined in four of the patients with SSPE by lymphoproliferation and were not significantly different from those in five healthy controls. The results demonstrate humoral and cellular immune responses to M protein in patients with SSPE and indicate that it is unlikely that a defect in the immune response to this virus component accounts for the disease process in the patients studied.

Adolescent↗
PubMed1986

Polypeptide specificities of measles virus-reactive T cell lines and clones derived from a patient with multiple sclerosis.

Eleven cloned and uncloned measles virus-specific T cell lines were generated from peripheral blood lymphocytes obtained from a patient with multiple sclerosis and were assayed for measles polypeptide specificity. Three clones reacted specifically with the fusion (F) protein and one recognized the hemagglutinin (HA). Two reacted with whole virus but not with any of the purified proteins. Five cell lines proliferated in response to multiple measles polypeptides. The addition of anti-HA or anti-F monoclonal antibodies to two of the multispecific cell lines each resulted in partial suppression of the proliferative response to whole virus by the cell lines. Two of the three F-reactive clones recognized antigen in association with a subgroup of HLA-DR4; the third responded to F only in the presence of autologous antigen-presenting cells. Of the two clones that reacted only with whole virus, one was restricted to DP3 and one to autologous cells. The HA-specific clone was DP3 restricted. Several cell lines recognized multiple measles polypeptides in association with a single HLA antigen. Recognition of individual measles polypeptides does not segregate with specific genetic restriction elements.

Antigens, Viral↗
PubMed1985

Myelin basic protein-specific T cell lines and clones derived from SJL/J mice with experimental allergic encephalomyelitis.

Myelin basic protein (BP)-specific T-cell lines and clones have been derived from SJL/J mice which had been sensitized with BP in complete Freund's adjuvant. Cell lines which were initiated and maintained in the presence of BP were specific for this antigen. Cell lines specific for tuberculin-purified protein derivative (PPD) were also established. BP-reactive cell lines maintained for 1 month in culture produced experimental allergic encephalomyelitis (EAE) when transferred to recipient mice. The number of cells required was only slightly less than that necessary for transfer of disease after 3-day culture of sensitized lymph node cells. In contrast, proliferative responses to BP were significantly enhanced after 1 month in culture. Cell lines lost the capacity to transfer EAE after 4 months in culture, but retained a vigorous proliferative response to BP. Similarly, cloned BP-reactive T cells failed to transfer disease, even when recipient mice were treated with IL-2, pertussis vaccine, or low-dose irradiation. Serial FACS analyses demonstrated alterations in cell surface antigen expression, particularly loss of reactivity with anti-Ia antibody, which correlated temporally with loss of ability to transfer disease. Persistence of antigen-induced proliferation by both cloned and uncloned T-cell lines should render these populations suitable for detailed study of the T-cell BP receptor.

Animals↗
PubMed1979

Detection of B cell antigens in multiple sclerosis. Use of serum from multiparous women.

Sera from two multiparous wives of patients with multiple sclerosis (MS) were used to detect B cell antigens in other patients. With serum X, 11 of 16 patients were positive as compared with ten of 16 controls (.05 less than P less than .1). With serum Y, a positive response was found in 11 of 16 patients and two of 23 controls (P less than .0005). Ten of the 11 patients who were positive with serum Y were also HLA-Dw2, which suggests that the B cell antigen detected by this serum is linked to Dw2. Three of four Dw2-positive controls were negative with serum Y, which raises two alternative hypothetical possibilities concerning the B cell antigen. These findings indicate that serum from multiparous wives may be an important tool in the investigation of the genetic components associated with MS.

Antigens↗
PubMed1978

Quantitation of IgG, IgA and IgM in the CSF by radioimmunoassay.

A radioimmunoassay (RIA) for quantitating IgG, IgA and IgM in unconcentrated CSF has been developed. The amounts and percentages of these immunoglobulins in CSF from 31 normal individuals were determined. Using these values as normal, CSF from patients with syphilis, encephalitis, subacute sclerosing panencephalitis (SSPE), and multiple sclerosis (MS) was studied. Abnormalities were detected, indicating the potential relevance of more extensive study of the CSF immunoglobulins. CSF from patients with myotonic dystrophy and myasthenia gravis was normal. RIA was compared with rocket electroimmunodiffusion (EID) for the quantitation of IgG. Although RIA consistently gave lower absolute values, both assays reliably detect elevated IgG in CSF. However, an advantage of RIA is its capacity to quantitate IgA and IgM.

Humans↗
PubMed1978

Increased CSF IgM in multiple sclerosis.

CSF IgM levels have been measured by radioimmunoassay in 56 patients with MS, 62 patients with other neurologic diseases, and 31 normal controls. Forty-eight percent of the patients with MS had a raised CSF IgM level compared with 5 percent of the patients with other diseases. The IgM level did not correlate with the IgG level. Forty percent of the MS patients with normal IgG levels had high IgM levels. No relationship was found between the CSF IgM level and length or severity of the MS, relapses, or steroid therapy. Attempts to identify the IgM as being anti-measles were unsuccessful.

Antibodies, Viral↗
PubMed1976

The disposition and pharmacokinetics in humans of 5-azacytidine administered intravenously as a bolus or by continuous infusion.

The disposition of 5-[4-14C]azacytidine, administered i.v. as a bolus or continuous infusion, was studied in cancer patients. After bolus, plasma 14C levels exhibited as multiphasic disappearance pattern; half-life (t1/2, beta phase) = 3.4 to 6.2 hr. Of 14C in plasma, less than 2% was associated with 5-[4-14C]azacytidine 30 min after dose. The ratios of 14C levels were: red cells/plasma, approximately 0.8; leukocytes/plasma, 1.1 to 2.3; nucleic acids/leukocytes, 0.2 to 0.43; sputum/plasma, 0.05 to 0.17. Urinary excretion (3 days) accounted for 73 to 98% of 14C, LEss than 1% in feces. The relative concentration of 5-azacytidine in plasma with continuous infusion stayed higher than with bolus; urinary excretion was similar. Fewer side effects were observed with continuous infusion than with bolus. The stability of 5-azacytidine was determined in various media at several temperatures by thin layer chromatography and nuclear magnetic resonance. At 20 degrees in Ringer's lactate (pH 6.2), the t1/2 was 94 to 100 hr. Stability increased with lowering of temperature and pH. From our data we conclude that 5-azacytidine should be given by continuous infusion rather than as a bolus.

Azacitidine↗
PubMed1975

Enrichment of colony forming cells by methotrexate and isokinetic density gradient centrifugation.

Purification of target cells responsive to granulopoietic regulators would be of importance in understanding their mechanism of action. Previous studies have shown that mouse marrow could be enriched 3- to 7-fold with respect to agar colony forming cells (CFU-C) by appropriately scheduled doses of Methotrexate. To further increase this enrichment, such marrow has been subjected to centrifugation through an isokinetic gradient of Ficoll in culture medium. Under optimal conditions (17.5 min at 77.5 X g) the combination of chemotherapy and velocity sedimentation yielded a 17-fold enrichment of CFU-C's.

Animals↗