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Biomedical subjects

B M Jones

Publications and source records attributed to B M Jones.

At least 127 records · Page 7Linked to original sources

Effects of interferon-gamma therapy on thyroid function, T-lymphocyte subpopulations and induction of autoantibodies.

Treatment with human leucocyte interferon (IFN alpha) has been associated with the development of thyroid autoimmunity and hypothyroidism, but it is not certain whether this phenomenon was a result of contamination with IFN gamma, which induced HLA class II antigen expression on T-lymphocytes. We prospectively studied 11 subjects (5 females and 6 males; mean age, 26.8 yr; range, 18-36) with chronic active hepatitis B who were randomized to receive recombinant human IFN gamma (rhIFN gamma; 10(6) U/m2.day, im, 3 times/week) for 16 weeks. Goiter was not present, and no patient had a history or family history of autoimmune diseases. Serial thyroid functions, including serum T4, T3, free thyroid hormone index, free T4 and TSH before, during, and on subsequent follow-up for a period of 1 yr were all normal. Eight patients had adequate serial samples for study of serological and lymphocyte subpopulations. None of the patients treated with rhIFN gamma developed thyroglobulin or thyroid microsomal antibodies. However, four patients developed antinuclear and smooth muscle autoantibodies during or after rhIFN gamma treatment. Treatment with rhIFN gamma resulted in a significant increase in circulating T-lymphocytes and HLA-DR-positive T-cells (P less than 0.05), with equal proportions of circulating CD4+ and CD8+ T-cells becoming DR positive. The percentage of HLA-DR-positive T-cells remained elevated after discontinuation of rhIFN gamma. Also, rhIFN gamma treatment led to a decrease in the number of circulating granulocytes and interleukin-2 receptor-positive cells. In conclusion, we did not observe any thyroid dysfunction or thyroid autoimmunity in our patients treated with the studied dose of rhIFN gamma, but induction of other autoantibodies was observed.

Adolescent↗

Minimal change glomerulopathy in two patients after thymectomy.

Two myasthenia gravis patients developed nephrotic syndrome due to minimal change glomerulopathy 3 to 14 years after thymectomy for malignant thymoma. Impaired cellular and humoral immunity has been documented in patients with thymoma and persists after thymectomy. The occurrence of minimal change disease lends support to the hypothesis that the glomerulopathy is secondary to T-cell dysfunction, resulting in production of a lymphokine which increases glomerular basement membrane permeability.

Adult↗

Comparison of monocyte separation methods using flow cytometric analysis.

We isolated normal, nonactivated human monocytes from peripheral blood by four different methods: (1) rosetting with sheep erythrocytes pretreated with 2-aminoethylisothiouronium bromide hydrobromide (AET) followed by monoclonal antibody (OKT3 (CD3), B1 (CD19), Leu7, Leu11 (CD16] and complement treatment; (2) adherence to gelatin/plasma-coated flasks; (3) adherence to plastic dishes; and (4) separation by the Sepracell technique. We monitored these monocyte separations by determining cell recoveries, OKT4A+ lymphocyte contamination, monocyte binding to human immunodeficiency virus (HIV), number of non-specific esterase-positive cells, and proportion of mononuclear cells reactive with a battery of monoclonal antibodies specific for monocytes. Our results indicate that of the four methods compared, adherence to gelatin/plasma-coated flasks produced the highest purity, recovery, and satisfactory binding to HIV with the fewest contaminating CD4+ T cells.

Antibodies, Monoclonal↗

Myelodysplastic syndrome with trisomy 8 in an adolescent with Fanconi anaemia and selective IgA deficiency.

We describe a patient with growth failure and multiple congenital anomalies characteristic of Fanconi anaemia, but without the classical feature of progressive bone marrow hypoplasia. Following treatment with growth hormone for a period of 8 years, he presented with myelodysplastic syndrome and a karyotypically abnormal clone in the bone marrow (47,XY,+8). The diagnosis of Fanconi anaemia was supported by the induction of abnormally high levels of characteristic chromosome aberrations in peripheral lymphocytes following exposure in vitro to the bifunctional alkylating agent mitomycin C. Immune function studies also identified a selective IgA deficiency. The relative importance of interacting constitutional and exogenous factors involved in the development of preleukaemia in this patient is discussed.

Adolescent↗

Relation between the rate of cell movement under agarose and the positioning of cells in heterotypic aggregates.

Single-cell suspensions prepared from 9-day-old chick tissues (skeletal muscle, liver, and neural retina) were used to investigate a possible relationship between intrinsic mobilities of different cell types and their positioning behavior in mixed (heterotypic) cellular aggregates. The relative mobilities of the three cell types, determined by comparing their ability to migrate under an agarose layer, was muscle greater than liver greater than neural retina. The gyratory shaker method was employed to produce heterotypic aggregates from mixed suspensions of muscle, liver, and neural retina cells and the tissue-specific positioning of cells after 24 h in culture was determined from histological and autoradiograph sections. The hierarchy for "inside" positioning of segregated cells was muscle greater than liver greater than neural retina cells, correlating with the rate of movement of these cells in the migration assay. The implication of the results is that relative speed of movement may determine the positioning of cells in heterotypic aggregates.

Animals↗

Lymphocyte immunophenotyping at the Centers for Disease Control: the program and special studies.

Lymphocyte immunophenotyping has been done at the Centers for Disease Control since 1981. The technology is constantly evolving, and changes have been instituted to keep up with and improve this technology. In the last 7 years we have analyzed approximately 8300 specimens from patients and persons at risk in projects related to the acquired immunodeficiency syndrome. Though several subsets of lymphocytes have been found to be increased or decreased in HIV infection, no lymphocyte determination is more sensitive than CD4 alone in predicting the outcome of human immunodeficiency virus infection.

Acquired Immunodeficiency Syndrome↗

Serial determinations of HIV-1 titers in HIV-infected homosexual men: association of rising titers with CD4 T cell depletion and progression to AIDS.

Lymphocyte subset enumerations, antibody titers to specific proteins of human immunodeficiency virus (HIV), and measurement of infectious HIV titers in peripheral blood mononuclear cells were performed on serial blood specimens from 15 HIV-infected homosexual men with chronic lymphadenopathy syndrome (LAS); 6 of these men have subsequently progressed to AIDS (progressors), and 9 have remained clinically stable (nonprogressors). For the earliest samples studied, no test distinguished those who would progress to AIDS from those who have not. The two groups diverged significantly about 1 year before AIDS diagnosis in the progressor group. Virus titers rose in progressors but remained relatively stable in nonprogressors. CD4 T cells and the CD4 T cell subset, 4B4, declined more rapidly in progressors than in nonprogressors. HIV antibody titers tended to decline in progressors, but the differences were significant only for antibody and to the pol-encoded proteins, p51/65, and the gag-encoded polyprotein, p55. Before the onset of clinical AIDS, progressors are distinguished from nonprogressors by markedly different rates of CD4 cell depletion and virus replication, but the elements that control these dynamics remain to be defined.

AIDS-Related Complex↗

Comparison of the in vitro activities of fenticonazole, other imidazoles, metronidazole, and tetracycline against organisms associated with bacterial vaginosis and skin infections.

The in vitro antibacterial activity of the antifungal compound fenticonazole was compared with those of clotrimazole, miconazole, tetracycline, and metronidazole against 177 strains of bacterial species associated with either bacterial vaginosis (BV) or skin infections by agar dilution MIC determinations. BV-associated Bacteroides isolates of the Bacteroides melaninogenicus-B. oralis group, Gardnerella vaginalis, Mobiluncus spp., and anaerobic, gram-positive cocci were highly susceptible to fenticonazole, clotrimazole, and miconazole; but Bacteroides spp. not associated with BV, Bacteroides ureolyticus and the Bacteroides fragilis group, were resistant. All Bacteroides strains were susceptible to metronidazole, but the susceptibility of G. vaginalis and Mobiluncus spp. varied. Among the skin bacteria, Staphylococcus aureus, coryneforms, and streptococci were highly susceptible to the imidazoles; but Staphylococcus epidermidis strains were generally resistant. This antibacterial activity may give fenticonazole a useful role in the topical treatment of vaginal discharge and in mycotic skin infections that are superinfected with bacteria.

Antifungal Agents↗

Double-marker analysis of B lymphocyte subsets using a combination of immunofluorescence and rosetting with immunomagnetic beads.

Double-marker assays were developed for enumerating CD5+ B-cells and CD25+ activated B-cells. To measure CD5+ B-cells, CD19+ (pan B-specific) cells were first isolated from peripheral blood mononuclear cells using anti-Leu12-coated immunomagnetic beads (Dynabeads). Positively selected cells were stained for surface immunoglobulin (sIg) and then incubated with anti-Leu1-coated Dynabeads. Fluorescent cells which also bound Dynabeads could be readily enumerated. The proportion of CD5+ B-cells was found to be significantly elevated in 9 of 20 patients with definite rheumatoid arthritis. B-cells bearing the interleukin-2 receptor (IL-2-R, CD25) were identified in pokeweed mitogen-stimulated PBM by sIg fluorescence and rosetting with anti-Tac-labelled Dynabeads. The kinetics of CD25 expression following activation were found to be different for B- and non-B-cells.

Antigens, CD↗

Screening for pre-leukaemia.

The pre-leukaemic state includes a variety of haematological conditions which in some patients precede the onset of acute leukaemia. These abnormalities may be primary or secondary to a known genetic insult. In some cases the condition may be associated with one of the constitutional syndromes characterised by genetic instability. The appropriate laboratory investigation to determine diagnosis and prognosis are examined.

Humans↗

The role of soluble immune response suppressor lymphokine in the prediction of steroid responsiveness in idiopathic nephrotic syndrome.

The role of serum soluble immune response suppressor (SIRS) lymphokine in the prediction of steroid responsiveness in idiopathic nephrotic syndrome was investigated. Serum SIRS was detected by its capacity to suppress the induction of plaque forming cells in pokeweed mitogen-stimulated in vitro lymphocyte culture in a dose dependent manner, and specificity was determined by the ability of monoclonal anti-SIRS coated beads to specifically absorb the suppressor activity. Serum SIRS was present in 7 of 18 patients with steroid responsive nephrotic syndrome and in 1 of 6 patients with nephrotic syndrome who were resistant to steroid treatment. It was also found in 2 of 4 patients with nephrotic syndrome which would be expected to be resistant to steroid treatment, in 2 of 10 patients with steroid responsive nephrotic syndrome in remission and in 2 of 8 normal healthy controls but was absent in 8 patients with non-nephrotic proteinuria secondary to a variety of renal disease. It was concluded that, although serum SIRS was present more often in patients with steroid responsive nephrotic syndrome, it is not a sensitive enough assay for predicting the response to treatment.

Humans↗

Psychological adjustment after cardiac transplantation.

Cardiac transplantation is viable therapeutic alternative for patients with end-stage heart disease, which offers a favourable short- and medium-term prognosis. The survival has improved from 20% of patients who survived at one year after transplantation in the 1960s to the present figures of 80%-85% of patients who are alive at one year, and 50%-70% of patients who are alive at five years, after transplantation. Therefore, it seems timely to focus attention on the psychological well-being of cardiac-transplant recipients. The medical literature is scant in regard to the psychiatric and the psychosocial impact of cardiac transplantation on recipients, and a systematic and prospective study of the psychosocial adaptation of recipients is lacking. Since 1984, we have been studying the emotional impact of cardiac transplantation on recipients and their families. This article presents the results for a group of recipients who have been assessed before transplantation, then followed-up at discharge from hospital and at four, eight and 12 months after transplantation. The study attempted to quantitate the recipients' anxiety, depression, body image and subjective quality of life by way of standardized self-assessment questionnaires. The recipients' satisfaction with relationships or their marital situation also was reported, as were their degree of rehabilitation at 12 months and their attitudes to various aspects of treatment after the transplantation. Before the transplantation, 53% of patients reported an increase in anxiety and 34% of patients recorded scores that indicated mild-to-moderate levels of depression. Thirty-seven per cent of patients showed a deterioration in the quality of their lives and 34% of patients had a negative body image. After the transplantation, significant improvements occurred in all parameters, which were maintained at follow-up.

Adaptation, Psychological↗

In vitro activity of azithromycin and erythromycin against organisms associated with bacterial vaginosis and chancroid.

The in vitro activity of the new macrolide azithromycin and erythromycin against Haemophilus ducreyi, Gardnerella vaginalis, Bacteroides spp. and Mobiluncus spp. was compared. Gardnerella vaginalis, Mobiluncus spp. and Haemophilus ducreyi were highly susceptible to both agents but azithromycin was more effective overall against all three groups of organisms. The activity of both antibiotics against Bacteroides spp. varied greatly, but azithromycin was again more active. Collectively, 62% of all Bacteroides strains were susceptible to erythromycin (MIC 1 mg/1) and 74% were susceptible to azithromycin.

Azides↗

Experience with the "floating forehead".

The effectiveness of the "floating forehead" operation for treating brachycephaly in infants has been assessed. All children who had undergone this procedure at the Hôpital des Enfants Malades between 1977 and 1984 were reviewed retrospectively by an independent observer. Particular attention was paid to the effects on cranial growth, facial growth and morphology.

Acrocephalosyndactylia↗

Phenotypic distribution of T cells of patients who have subsequently developed AIDS.

In a previous study of asymptomatic homosexual men, we found that CD8+ T-cell levels were higher in homosexual men infected with the human immunodeficiency virus (HIV) than in uninfected homosexual men because of higher numbers of CD8+ T cells that do not express the Leu15 marker, a phenotype associated with cytotoxic function. Among infected men, there was a positive correlation between the number of CD8+Leu15- T cells and the number of CD4+ T cells. If CD4+ T-cell levels are taken as a measure of severity of HIV infection and immunodeficiency, these results suggested that higher CD8+Leu15- cells may represent a phenotypic profile associated with less severe infection or better control of infection. In the present study, we extend the analysis to include a group of men who progressed to AIDS but were studied well before the onset of AIDS, and we compare results of CD8 subset analyses with results of infected men who have not progressed to AIDS. Phenotypic subsets associated with helper, suppressor, cytotoxic, and natural killer cell function were determined by two-color immunofluorescence. The only phenotypic subset that distinguished men who progressed to AIDS from those who have not was lower numbers of CD4+ T cells in the former group. If CD8+Leu15- cell numbers (or other phenotypic subsets examined) reflect effective control of HIV infection, the relationship is not strong enough to be of prognostic or predictive value with respect to outcome of infection.

Acquired Immunodeficiency Syndrome↗

Direct anastomotic assessment for postoperative microvascular monitoring.

An experimental comparison of two techniques for direct monitoring of anastomoses postoperatively is presented. Arterial differential temperature measurements indicated arterial occlusion (n = 24) in island flaps by mean temperature decreases in the affected artery of 0.5 degrees = C, but temperature changes in cases of venous occlusion (n = 17) were small (mean, 0.2 degrees C), inconsistent, and not of predictive value. The technique did not distinguish success (n = 4) from failure (n = 2) in experimental free flaps, and occlusion of deep arteries produced little or no change in the arterial wall temperature. In contrast, an implanted ultrasound Doppler probe reliably indicated arterial and venous occlusion in island flaps (n = 10), because in both circumstances the mean arterial Doppler signal invariably decreased to 0. The two could be distinguished between by changes in Doppler sound and instantaneous signal. In experimental free flaps, success (n = 10) was clearly distinguished from failure (n = 3) by characteristic patterns of Doppler sound and signal. Arterial differential thermometry had serious limitations, but implanted ultrasound Doppler showed great potential as a postoperative monitor applicable to all microvascular procedures.

Anastomosis, Surgical↗