Gradual hearing loss with bilateral labyrinthine hemorrhage in chronic myelogenous leukemia.
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Cochlea↗
Biomedical subjects
M Cherchi
Publications and source records attributed to M Cherchi.
Oesophageal motility in adult coeliac disease.
Coeliac sprue is a relatively frequent disease with protean clinical manifestations. Recent studies suggest that gastrointestinal motor abnormalities may explain some symptoms complained of by such patients. We investigated whether coeliac patients have oesophageal motor abnormalities from both a clinical and a physiological point of view. Thirty-six consecutive adult sprue subjects (14 during the florid phase and 22 on gluten-free diet) were studied. A clinical questionnaire on gastrointestinal symptoms (with emphasis on those of oesophageal origin) was administered. Moreover, 18 patients (13 on free and five on gluten-free diet) gave their consent for oesophageal manometry and eight subjects for pH-metry also. Oesophageal clinical symptoms were compared with those of 144 age- and sex-matched controls from a general population sample, and manometry with that of 34 healthy volunteers. Of coeliac patients 50% complained of dysphagia (P < 0.001 vs. controls) and 14% noncardiac chest pain (P = NS vs. controls). Manometric examination showed motor abnormalities in 67% of the subjects examined, consisting of nutcracker oesophagus, hypotonic lower oesophageal sphincter associated with simultaneous contractions, and frequent repetitive (> 3 peaks) contractions. These abnormalities were equally distributed among free and gluten-free diet patients. pH-metry showed only one pathological reflux out of eight subjects studied. We conclude that patients with coeliac sprue may display abnormal oesophageal motility. This confirms previous studies suggesting that gastrointestinal motor abnormalities should probably be added to the clinical spectrum of the disease.
Adult↗
Detection and characterization of apoptotic peripheral blood lymphocytes in human immunodeficiency virus infection and cancer chemotherapy by a novel flow immunocytometric method.
We have developed a quantitative and sensitive flow cytometric method for the detection of human apoptotic lymphocytes that, unlike previously described assays, allows their identification in mixed populations of peripheral blood leukocytes as well as their immunophenotyping. Apoptotic lymphocytes are identified on the basis of peculiar light scatter changes, reflecting their smaller size and their modified nucleus/cytoplasm organization, and of the decreased expression of surface CD45 molecules. Based on these criteria, apoptotic lymphocytes generated by exposure to ionizing radiation can be easily distinguished from viable cells and from necrotic lymphocytes generated by treatment with antibody and complement. Using this assay, we reappraised the phenomenon of the in vitro apoptosis of lymphocytes from patients with human immunodeficiency virus (HIV) infection. Lymphocytes from HIV patients, unlike those from normal HIV-negative subjects, undergo apoptosis upon simple in vitro culture. We found that the percentages of lymphocytes undergoing apoptosis were significantly higher in patients with low CD4 cell counts (< 400/microL) than in patients at earlier stages (> 400 CD4 cells/microL). However, phenotypic analysis disclosed that apoptotic lymphocytes generated in these cultures were mostly CD8+ T cells and CD19+ B cells. Thus, in contrast to what has been previously suggested, the phenomenon of in vitro lymphocyte apoptosis might not be pathogenetically related to the depletion of CD4+ T cells in acquired immunodeficiency syndrome. Nevertheless, it might represent an useful marker of disease progression. Our assay allows the analysis of unfractionated peripheral blood leukocytes and thus the identification of apoptotic lymphocytes circulating in vivo. Apoptotic lymphocytes could indeed be detected in the circulation of a patient with cancer shortly after high-dose cytotoxic chemotherapy. By contrast, no apoptotic lymphocytes could be detected in vivo in patients with early or advanced HIV infection.
Adult↗
Activated and "memory" phenotype of circulating T lymphocytes in intrauterine life.
We examined the expression of T cell markers in the peripheral blood of five immunologically normal human fetuses at 18-20 weeks of gestational age. The distribution of T cells expressing CD1, CD3, CD4, CD8, CD56, and the alpha/beta and gamma/delta receptors for antigen was comparable to that of newborns and normal adults, except for the absence of gamma/delta cells expressing the delta TCS-1 epitope. The V beta repertoire, as evaluated by two-color flow cytometry using mAbs to specific V beta families, was also comparable to that of adult samples. A significant fraction (8.9 to 16.4%) of fetal CD3+ T cells expressed the alpha chain of IL-2R (CD25) in the absence of HLA-DR; this suggests that antigenic stimuli trigger, during intrauterine life, an unusual pathway of T cell activation. Consistent with this, 7 to 27% of fetal T cells were found to express the CD45R0 marker of "memory" cells.
Antigens, CD↗
Absence of antibodies to human herpesvirus-6 in patients with slowly-progressive human immunodeficiency virus type 1 infection.
To evaluate a possible role for Human Herpesvirus-type 6 (HHV-6) coinfection as a co-factor in the progression of HIV-1 disease, we investigated the prevalence of seropositivity for HHV-6 in a cohort of HIV-1 infected patients. These patients were retrospectively divided into two groups according to the decline of CD4+ T cells during the follow up: 11 were classified as rapid decliners (less than 400 CD4+/cmm within 1 year), and 38 as slow decliners (greater than 400 CD4+/cmm after at least 4 years' follow up). HHV-6 antibodies were detected by a commercial immunofluorescence assay and by a Western blotting assay developed in our laboratory. Our results show that Western blot appears to provide results satisfactorily free of false positivities. We found that the frequency of HHV-6 seropositivity was significantly lower in the group of slow decliners, compared both to rapid decliners and to the general population. These data suggest a role for HHV-6 co-infection in the progression of HIV-1 disease.
Adolescent↗
T-lymphocyte reactivity to the recombinant mycobacterial 65- and 70-kDa heat shock proteins in multiple sclerosis.
Owing to their conservation and immunogenicity, heat shock proteins (hsps) represent a class of potential autoantigens. Moreover, they could be targets for gamma delta T lymphocytes, which are prominent in various immune disorders. We studied the T cell proliferative primary responses to recombinant M. bovis 65 kDa hsp (hsp65) and M. tuberculosis 70 kDa hsp (hsp70) in 31 patients with multiple sclerosis (MS), 19 patients with other neurological diseases (OND) and 19 healthy individuals. Positive responses to hsp70, but not to hsp65 were significantly more frequent in patients with MS than in patients with OND or in healthy individuals. In order to verify and refine these results and to characterize the hsp reactive T lymphocytes, we screened 147 PPD-specific long-term T cell lines (76 from 10 patients with MS and 71 from 12 healthy donors) for their proliferative response to hsp65 and hsp70. hsp70-reactive T lines were significantly more common in patients with MS than in healthy controls. The number of T lines responding to hsp65 increased in the MS group only slightly. In 19 T lymphocyte lines from patients with MS and healthy donors, a cytofluorometric analysis was performed with special attention paid to distinct T cell receptor gamma delta determinants. With one exception, in each line the population of gamma delta T cells remained a minority. We conclude that an increased T cell response to mycobacterial hsp70 may be present in patients with multiple sclerosis.
Adolescent↗
Relative increase of T cells expressing the gamma/delta rather than the alpha/beta receptor in ataxia-telangiectasia.
In ataxia-telangiectasia, B-cell and T-cell deficiencies are thought to be due to a defect of rearrangements of immunoglobulin and T-cell receptor genes. T cells recognize antigens through two types of CD3-associated receptors: alpha/beta chains on mature cells and gamma/delta chains mostly on immature cells. We studied 10 patients with ataxia-telangiectasia and found that most had a relative increase of circulating T cells bearing gamma/delta receptors rather than alpha/beta receptors, as compared with normal subjects (P less than 0.001). Patients with other immune deficits, including eight with common variable immunodeficiency, one with Wiskott-Aldrich syndrome, two with hyperimmunoglobulinemia E syndrome, and one with severe combined immunodeficiency, had normal ratios of gamma/delta-bearing to alpha/beta-bearing cells. A marked predominance of gamma/delta-bearing T cells was found in a patient with a primary T-cell defect. The relative increase in gamma/delta-bearing T cells in the patients with ataxia-telangiectasia was largely accounted for by cells that reacted with the monoclonal antibody BB3, an apparently distinct subset of T cells that selectively express the C gamma 1 gene product of the T-cell receptor. Although they had normal ratios of gamma/delta-bearing to alpha/beta-bearing T cells, the patients with common variable immunodeficiency had a significant increase (P = 0.01) in the number of T cells expressing C gamma 2 that reacted with the monoclonal antibody delta-TCS-1. We conclude that the increased ratio of gamma/delta-bearing to alpha/beta-bearing T cells in ataxia-telangiectasia may reflect both a recombinational defect that interferes with T-cell and B-cell gene rearrangements and an inability to repair damage to the DNA.
Adolescent↗
CD4 as the receptor for retroviruses of the HTLV family: immunopathogenetic implications.
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Autoantibodies↗
Cellular and humoral modifications during response to HBsAg vaccine in healthy subjects: comparison between French and American vaccines.
Two groups of 18 healthy adults, chosen from a risk population, were vaccinated against hepatitis B virus with French (Hevac B, Pasteur) or American (HB-VAX, MSD) vaccine; immunological and biochemical parameters (HBsAb titers, Ig, IgM-rheumatoid factor (IgM-RF) levels, autologous mixed lymphocyte reaction (AMLR), T4/T8 ratio, lymphocyte migration inhibition test (LMIT) with specific antigen and transaminase levels) were compared at preselected time intervals. The vaccines were found to be clinically safe, as documented by the absence of demonstrable side effects and changes in serum transaminase levels. The positivity of the LMIT test demonstrated an early immunization on day 45 in all subjects tested, along with a marked reduction in AMLR, independent of the vaccine used. A slightly higher, though not statistically significant, percentage of seroconversion was observed for the Pasteur vaccine. This same preparation induced a significant increase in the main Ig classes and in Ig;-RF levels on day 45. This data indicates that aspecific modification of the immune system occur to a greater extent with Hevac B, presumably for its lower degree of purification. Thus, despite the slightly lower efficacy, the HB-VAX might be the preparation of choice in subjects with immunological disturbances.
Adult↗
Alpha interferon treatment in HIV infected patients restores gamma interferon production in vitro.
We studied gamma interferon (IFN) production in vitro by lymphocytes from 5 patients with AIDS and 2 with advanced AIDS-related complex (ARC) before and during treatment with r-alpha 2a IFN at low doses, for up to 12 months. Patients were divided in responders (three) and non responders according to clinical data after six months of treatment. No immunological parameter was predictive of the clinical results. We found that subpopulations of T lymphocytes and lymphoproliferative response were not significantly modified in responders, while severely decreased in non responder patients. In 5/7 cases we observed a small but significant increase of gamma IFN production after six months of therapy, which rose to normal values after 12 months in responders.
AIDS-Related Complex↗
Immunological responses of patients with recurrent herpes genitalis.
Immunological responses of patients with recurrent herpes genitalis (RHG) were assayed in comparison to those of patients affected by recurrent herpes labialis (RHL) and to those of normal seropositive and seronegative controls. Total T cells were normal while a significant (p less than 0.001) reduction of cells with helper phenotype was found only in people with RHG, who were also lacking specific cell-mediated immunity (CMI) to herpes simplex virus (HSV) antigen. HSV-type 2 was demonstrated in their active lesions. Number of human NK-1 positive (HNK-1 +) cells was increased in RHG showing an inverse correlation with depressed natural killer (NK) activity. These abnormalities were found irrespective or not if tests were carried out during the active phase of the disease or during quiescence and were confirmed during the 2-year follow-up period to which patients were submitted. Similar abnormalities were found in RHL only during the active phase and reversed to normal during quiescence. Our data indicate the presence of specific cellular and NK unresponsiveness in subjects with severe and long-lasting herpes genitalis.
Adolescent↗
Chronic T-cell leukaemias. III. T-colonies, PHA response and correlation with membrane phenotype.
The functional capacity of T lymphocytes from 28 cases of chronic T-cell leukaemia--T-CLL, T-PLL, T-LCL and Sézary syndrome--was evaluated in a T-colony forming system and in a PHA response assay. Reduced or absent T-colony growth was observed in 23 cases (82%) while in five the growth was normal. Although a good correlation was generally observed between colony formation and PHA transformation, in a few cases a low PHA response was accompanied by moderate colony growth and vice versa. Characterization of the leukaemic T lymphocytes using monoclonal antibodies (OKT series) indicates that cases with a helper/inducer phenotype (OKT4+) showed moderately reduced or near-normal T-colony numbers, whilst cases with a suppressor/cytotoxic phenotype (OKT8+)--confined to T-CLL in this study--had a very low or absent colony growth. The functional abnormalities reported here suggest that neoplastic T-cells with a helper/inducer phenotype show a low proliferative response in the assay systems used, although expressing mature T-cell characteristics. The low growth observed in T-CLL confirms that cells with a suppressor/cytotoxic phenotype form few T-cell colonies.
Cell Division↗
The membrane phenotype of T-prolymphocytic leukaemia.
Cells from 13 cases of T-prolymphocytic leukaemia (T-PLL) were studied with a battery of immunological techniques in order to define their membrane phenotype. All cases were E-rosette positive and were negative with OKT6, anti-HLA-DR, anti-Ig and M-rosettes; in 3, 20-30% of the cells had receptors for C3b. 7 cases had predominantly a 'helper/inducer' T-subset phenotype, (OKT4+, OKT8-) and 4 had a 'suppressor/cytotoxic' phenotype (OKT8+, OKT4-). Cells in 2 cases coexpressed OKT4 and OKT8 in 48% and 95% of prolymphocytes and in another, both OKT4 and OKT8 were negative. Terminal transferase (TdT) was negative by IF in all the cases, but a low positive level was detected biochemically in one. Although T-PLL appears to be heterogenous in respect of membrane phenotype, the observation of unexpected features in 8 of the cases raises the possibility that it may originate in a cell of intermediate maturation between late thymocytes and mature T-lymphocytes. These features plus the clinical manifestation of the disease - typical morphology, splenomegaly, lymphadenopathy, skin lesions, high WBC and aggressive clinical course - help define T-PLL as a distinct clinicopathological entity.
Aged↗
Unusual T-cell phenotype in advanced B-chronic lymphocytic leukaemia.
T-lymphocytes isolated by E-rosetting from 22 patients with B-cell chronic lymphocytic leukaemia (B-CLL) showed membrane phenotype features distinct from those of normal T-lymphocytes. These changes were particularly marked in advanced disease (Rai stages II, III, IV and WBC over 100x10(9)/l). The most significant finding was the demonstration, in 10 cases, of a major population of E-rosette positive cells (40-80%) unreactive with the OKT monoclonal antibodies against mature or immature T-cells; 15-30% of the cells were unreactive in seven other cases. A significant reduction in OKT4 positive (helper) lymphocytes was seen in 18 cases. The proportion of OKT8 positive cells was increased in two and normal or low in the rest. Only four patients with early disease (stages 0 and I) had a normal T-cell phenotype. These findings could explain abnormalities previously described in the T-lymphocytes of B-CLL and provide new insights into the pathogenesis of the disease.
Antibodies, Monoclonal↗
Heterogeneity of B-cell leukemias demonstrated by the monoclonal antibody FMC7.
A new monoclonal antibody, FMC7, was studied in 68 patients with chronic B-cell leukemia. All 17 cases of prolymphocytic leukemia (B-PLL) and 8 of 9 of hairy-cell leukemia were positive. In contrast, FMC7 was negative in 32 of 38 chronic lymphocytic leukemias (B-CLL; p less than 0.001) and 4 cases of B-cell lymphoma. Four of the 6 positive B-CLL cases were in "prolymphocytoid" transformation; two of them had bright membrane Ig (SmIg) staining and may represent an intermediate form between B-CLL and B-PLL. Although there was a tendency for the intensity of the immunofluorescence reaction with FMC7 and SmIg to change in parallel, FMC7 did not correlate with any Ig class. In addition, almost all FMC7-negative B-CLL had weak expression of SmIg. FMC7 is different from other monoclonal antibodies raised against B-lineage cells in that it recognizes only some subsets, presumably those at a late stage of maturation. This property confers diagnostic potential to this reagent and may contribute to the better characterization of the B-cell neoplasias.
Animals↗
Characterization of B-cell leukemias: a tentative immunomorphological scheme.
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B-Lymphocytes↗
Stimulation of chronic lymphatic leukaemia cells by pokeweed mitogen after treatment with neuraminidase-galactose oxidase.
CLL lymphocytes gave a low response upon stimulation with PHA or PWM in 3-day cultures. However, after treatment with neuraminidase-galactose oxidase (NGO), in the presence of PWM, CLL lymphocytes transformed into blasts and incorporated 3H-thymidine in 3-day cultures. This response of CLL lymphocytes was similar to that given by normal lymphocytes to PWM in 3-day cultures. The best stimulation of CLL lymphocytes was achieved when conditioned medium (CM) from normal T lymphocytes was present in PWM cultures. Purified B lymphocytes from CLL (T lymphocytes and monocytes removed) did not respond to PHA or PWM. However, after NGO treatment these cells were stimulated by PWM, but only in the presence of CM. PHA failed to stimulate NGO-treated CLL lymphocytes or purified B lymphocytes. This study shows that CLL lymphocytes, which usually fail to respond to mitogens, can be stimulated by PWM to proliferate after treatment with neuraminidase-galactose oxidase (NGO). This technique of B cell stimulation has been found useful in cytogenetic studies of B cell proliferative disorders.
B-Lymphocytes↗
Cell surface and enzyme markers of cord blood lymphocytes.
Human cord blood (CB) lymphocytes were studied with several markers for T- and B-cells and the results compared with those of adult peripheral blood (PB) samples. The proportion of E-rosettes was significantly lower in CB (mean 24.7+/-13.5 SD) than in PB (67.5+/-7.3 SD). Treatment with neuramidase produced a marked increase in the proportion of E-rosettes in CB (mean 47 +/-13.9 SD), still below the PB values. The proportion of CB lymphocytes showing block positivity with alpha-naphthyl-acetate-esterase correlated closely with the percentage of E-rosettes in neuraminidase treated cells. The percentage of H-rosettes (human RBC) was significantly higher in CB (7.2+/-6.0) than in PB (3.2+/-1.6 SD). Re-rosetting experiments showed that in CB about 30% of the E-positive cells formed H-rosettes, in contrast to 5% in PB. These findings indicate that in CB the real number of T-lymphocytes is higher than shown by conventional E-rosette formation. The proportion of B-lymphocytes, tested by surface immunoglobulins and by rosette formation with mouse RBC (M-rosettes), was similar in CB and in adult PB. A slight increase in cells with IgM on the surface was found in CB. The overall proportion of lymphocytes with negative B and T markers in CB is three times greater than in adult PB. Levels of the enzyme terminal deoxynucleotidyl transferase were marginally increased in CG; in two out of 41 samples the levels were above those found in normal bone marrow. CB may be a suitable model for the study of lymphocyte subsets with negative B and T markers in man.
Adult↗