Biomedical subjects
Publications and source records attributed to L Jackson.
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To examine the defect in cellular immunity in patients with acquired immunodeficiency syndrome (AIDS), we studied in vitro lymphocyte proliferation and interferon (IFN) release in response to cytomegalovirus (CMV) antigen and Concanavalin A mitogen in 40 homosexual men with AIDS, 10 homosexual men with chronic lymphadenopathy syndrome, 7 healthy homosexual men, and 18 healthy heterosexual subjects of either sex. CMV serology by an enzyme-linked immunosorbent assay and viral cultures for CMV were performed. Lymphocytes of patients with AIDS showed impaired CMV-specific release of IFN but normal mitogen-induced IFN release. The defect was not attributable to CMV infection per se. Cell proliferation in response to both CMV antigen and mitogen was impaired in patients with AIDS who had opportunistic infections. The defect could not be attributed to CMV viremia. We concluded that impaired release of IFN in response to a viral antigen is characteristic of lymphocytes in patients with AIDS and that this defect is distinct from a defect in mitogenic responsiveness, which coexists predominantly in patients with opportunistic infections.
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Herpesvirus infections were studied in persons with or at risk for the acquired immune deficiency syndrome (AIDS). The infections diagnosed were as follows: patients with AIDS, cytomegalovirus (CMV) in 34 of 34, Epstein-Barr virus (EBV) in 33 of 34, herpes simplex viruses (HSV) in eight of 34, and varicella zoster virus in four of 34; patients with chronic lymphadenopathy syndrome, CMV in eight of nine and EBV in nine of nine; in healthy homosexual men, CMV in five of 13 and EBV in seven of eight. Cytomegalovirus infections were frequently related to disease and death. Herpesvirus infections are frequent causes of serious diseases in AIDS. The prevalence of EBV and CMV infections in AIDS and the chronic lymphadenopathy syndrome may be the result of an important interaction between these viruses and the cause of AIDS.
Specific factors in a couple's history may influence the recurrence risk following repeated pregnancy loss (RPL). Couples with RPL were contacted several years following evaluation and information concerning subsequent pregnancies was obtained. Linear regression analysis was utilized to determine which factors in the history were significant predictors of pregnancy outcome following evaluation. A family history of RPL or a "genetic defect" was a highly significant predictor of subsequent unsuccessful pregnancies. Surgical, but not medical, treatment for RPL was a significant predictor of eventual successful outcome. The number of abortions prior to evaluation for RPL, presence of a liveborn child, maternal age at evaluation, and intercurrent infertility all failed to be significant predictors of pregnancy outcome after evaluation.
The Towne strain cytomegalovirus and a low-passage strain, Toledo-1, were compared for virulence and immunogenicity in healthy adult male subjects to determine the suitability of the Towne strain for vaccination. Five seropositive subjects who received the Toledo-1 strain developed infections ranging in severity from laboratory abnormalities to mild mononucleosis syndromes (mean incubation, 4.7 weeks). None of the four seronegative subjects receiving the Towne strain developed systemic infection, but all developed delayed local reactions at the injection sites. All subjects developed cytotoxic lymphocyte responses specific to cytomegalovirus, usually HLA-restricted, but these were of greater magnitude and duration in the Toledo-1 recipients. The latter also developed natural killer cell and interferon responses, atypical lymphocytosis, inversion of helper/suppressor cell ratios, and depressed responses to T-cell mitogens, none of which occurred in Towne strain recipients. The results further substantiate the avirulence and immunogenicity of the Towne strain cytomegalovirus.
While the role of cytogenetic study in couples with repeated pregnancy loss is well-established, little information is available for counseling these couples concerning future reproductive outcome. Couples evaluated by chromosome analysis for recurrent abortion between 1972 and 1979 were contacted by phone in 1981. Of those studied cytogenetically, 195 couples (50.1%) could be located, and information concerning outcome of subsequent pregnancies were obtained. Couples (91) with two consecutive pregnancy losses at the time of initial investigation had a 31.3% subsequent abortion rate, but most (68%) had at least one liveborn child. The rate of infertility following evaluation was slightly increased (18.7%), but that of prematurity (11.2%) and congenital anomalies (2.5%) was not. In contrast, couples with greater than or equal to 3 consecutive losses (84) experienced abortion in 45.7% of subsequent pregnancies, and only 54.8% of them eventually had a liveborn child. Again, the rate of infertility was increased (26.2%), but that of prematurity (10%) and congenital defects (3.2%) was not. Nine couples in which one individual was found to have a chromosome abnormality (two inversions and seven translocations) were considered separately. Of these, seven couples had nine liveborn offspring. Amniocentesis was performed in eight cases, with karyotypes showing a balanced translocation identical to that of the parent in 2. All children were phenotypically normal.
The recently described acquired immune deficiency syndrome (AIDS) is characterized by the occurrence of severe opportunistic infections and an aggressive form of Kaposi's sarcoma. A variety of profound defects in cell-mediated immunity have been reported in association with the AIDS, including deficiencies in natural killer (NK) cell activity and cytomegalovirus (CMV)-specific cytotoxicity. In the present study, the in vitro effects of interleukin-2 (IL-2) and interferon beta (IFN Beta) on these abnormalities were examined to assess the potential use of these lymphokines in the immunotherapeutic treatment of this syndrome. The peripheral blood lymphocytes (PBL) from six male homosexuals with AIDS and an active CMV infection exhibited markedly depressed NK cell and CMV-specific cytotoxic lymphocyte responses compared with uninfected, heterosexual control subjects. Incubation of PBL with IFN Beta enhanced the NK cell activity and the CMV-specific cytotoxicity of only one of six and neither of two AIDS patients, respectively, while enhancing the NK cell activity of all six control subjects. In contrast, IL-2 dramatically enhanced both the NK cell and the CMV-specific cytotoxic lymphocyte activities of all of the patients. These results indicate that IL-2 can substantially potentiate the depressed cytotoxic effector functions of PBL from AIDS patients, while IFN Beta has little effect.
We studied 58 recipients of bone-marrow transplants to evaluate immune responses to cytomegalovirus infection. Such infection developed in 43 patients; it was fatal in 12, nonfatal in 23, and present at death from other causes in eight. All patients had low or absent cytomegalovirus-specific cytotoxic lymphocyte activity before the onset of infection. Cytomegalovirus-specific cytotoxic responses developed in all survivors, whereas only two patients with fatal infection had even low-level cytomegalovirus-specific cytotoxic responses. Natural and antibody-dependent killer-cell activities were depressed both before and during infection in patients with fatal infections, but not in those who survived. The outcome of the infection did not correlate with the nature of the underlying disease, the type of transplant received, the pretransplantation cytomegalovirus-antibody status, or lymphocyte-proliferation responses to cytomegalovirus antigens or concanavalin A. The correlation between effective virus-specific cytotoxic response and recovery from infection indicates that these effector cells probably mediate recovery from cytomegalovirus infection.
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Prostaglandins have been shown to modulate water flow in anuran amphibian urinary bladders. These experiments examined which fatty acid precursor could be metabolized by bladders, and the effect of metabolites on osmotic water flow. Hemibladders were incubated with precursors or prostaglandins (1 microM) and water flow measured. In addition, hemibladders were incubated with 14C-labelled eicosatrienoic, arachidonic, or eicosapentaenoic acid, and products identified by thin layer chromatography. Addition of prostaglandins E1, E2 and I2 inhibited water flow. Eicosatrienoic acid did not affect water flow. Arachidonic acid inhibited basal water flow, an effect which was not completely reversed with the addition of indomethacin. Eicosapentaenoic acid stimulated water flow, and the stimulation was blocked with indomethacin. Frog urinary bladder did not synthesize any prostaglandins from 14C-eicosatrienoic acid. 14C-arachidonic acid was converted into PGE2 and PGD2. 14C-eicosapentaenoic acid was synthesized into compounds, presumably PGE3 and PGD3, with the opposite physiological effects of two-series prostaglandins. The data suggest that effects of prostaglandins on amphibian bladder depend on the substrate which is metabolized.
1 Changes in hepatic blood flow have been estimated by measurement of single-dose indocyanine green kinetics in groups of healthy individuals. 2 The effects of change in posture, exercise and ingestion of milk on estimated hepatic blood flow have been assessed. 3 The erect posture and exercise significantly decreased ICG clearance. However, no consistent change was noted after ingestion of milk. 4 The effects of the adrenoceptor blocking drugs phenoxybenzamine, propranolol and labetalol on hepatic blood flow were also assessed. 5 Propranolol and labetalol caused a significant fall in ICG clearance in the supine position. Phenoxybenzamine did not show a consistent change. 6 Posture, exercise and adrenoceptor blockade appear to be important variables affecting hepatic blood flow. They should be considered when kinetics of high-clearance drugs are measured, and may provide a useful model for the assessment of the effects of alterations in hepatic blood flow on the clearance of drugs.
Dapsone given over 14 weeks in a dose of 50 mg a day for 1 week and thereafter 100 mg a day was found to have a beneficial effect in rheumatoid arthritis when compared with placebo administration to a matched group of patients. Significant improvement in 5 out of 7 clinical measurements and in erythrocyte sedimentation rate, viscosity, C-reactive protein was found in those patients taking dapsone. There was significant improvement compared to the placebo group in 2 out of the 7 clinical measurements and again in all 3 acute-phase reactants. The drug was quite well tolerated over the 14-week duration of the trial. The tendency to cause haemolysis will be its main limiting factor as a practical alternative to other suppressive agents currently in use.
Blood pressure was measured in the rural and urban male and female Polynesian populations of Western Samoa to determine if differences existed in mean blood pressures or in the prevalence of hypertension between these groups. It was found that, in the urban population, both males and females had higher mean blood pressures and approximately double the prevalence of hypertension found in their rural counterparts. There was an age-related rise in mean blood pressure and in the prevalence of hypertension in all groups. Approximately half of the difference in mean blood pressure and hypertension prevalence between rural and urban groups appeared to be due to difference in adiposity. Age and body mass index were significantly and independently correlated with systolic and diastolic blood pressure in each group. The prevalence of hypertension was greater in obese subjects.
The prevalence of hypertension and the change in blood pressure with age were investigated in a Polynesian population (Tuvalu), and in a Micronesian population (Nauru) in the South Pacific region. Hypertension was present in 27.2 percent of the Nauruans and 11.1 percent of the Tuvaluans. Both population groups also showed a rise in mean blood pressure with increasing age--a phenomenon apparently absent in traditional-living populations of the world but present in western societies.
Electrocardiographic changes defined as probable or suspect ischaemic heart disease and coded according to the Minnesota coding system, were found in 14 (10.3 percent) of 136 Funafutians surveyed. Of these abnormal electrocardiograms, nine were classified as "probable" ischaemia and five as "suspect" ischaemia. There was a higher prevalence of electrocardiographic ischaemia in the female population compared with the male population of Funafuti. This is consistent with the greater degree of obesity and higher prevalence of diabetes previously reported in females in this population.