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Biomedical subjects

J Gotto

Publications and source records attributed to J Gotto.

6 recordsLinked to original sources

The impact of HBV-DNA fluctuations on virus-specific CD8+ T cells in HBeAg+ chronic hepatitis B patients treated with a steroid and lamivudine.

Restoration of anti-viral immune response may be a requisite for sustained virological response to treatment in chronic hepatitis B patients. Over a 13-month period, we examined the dynamics of hepatitis B virus (HBV)-specific CD8+ cells in six human leucocyte antigen (HLA)-A2+ hepatitis B e antigen (HBeAg)+ 'immunotolerant' chronic hepatitis B patients treated sequentially with corticosteroid and lamivudine. Our results show that the combination treatment did not result in a sustained restoration of anti-viral specific CD8+ cells in five of the six patients studied. However, HBV-specific CD8+ cells, despite being severely compromised, were not totally deleted. Paradoxically, steroid treatment was not associated with inhibition but with a minimal increase of the HBV-specific CD8 response, and we observed that nucleocapsid-specific CD8 responses were not rescued by stable and prolonged inhibition but became detectable after rapid rebounds of HBV replication. In most patients, the transient and minimal restoration of HBV-specific immunity was not associated with clinical benefits. Our results describe a dynamic relationship between HBV-specific CD8+ cells and HBV-DNA values, that could potentially be used for a better design of HBV treatment in HBeAg+ 'immunotolerant' chronic hepatitis B patients.

Adult↗

Sensorimotor adaptations to microgravity in humans.

Motor function is altered by microgravity, but little detail is available as to what these changes are and how changes in the individual components of the sensorimotor system affect the control of movement. Further, there is little information on whether the changes in motor performance reflect immediate or chronic adaptations to changing gravitational environments. To determine the effects of microgravity on the neural control properties of selected motor pools, four male astronauts from the NASA STS-78 mission performed motor tasks requiring the maintenance of either ankle dorsiflexor or plantarflexor torque. Torques of 10 or 50% of a maximal voluntary contraction (MVC) were requested of the subjects during 10 degrees peak-to-peak sinusoidal movements at 0.5 Hz. When 10% MVC of the plantarflexors was requested, the actual torques generated in-flight were similar to pre-flight values. Post-flight torques were higher than pre- and in-flight torques. The actual torques when 50% MVC was requested were higher in- and post-flight than pre-flight. Soleus (Sol) electromyographic (EMG) amplitudes during plantarflexion were higher in-flight than pre- or post-flight for both the 10 and 50% MVC tasks. No differences in medial gastrocnemius (MG) EMG amplitudes were observed for either the 10 or 50% MVC tasks. The EMG amplitudes of the tibialis anterior (TA), an antagonist to plantarflexion, were higher in- and post-flight than pre-flight for the 50% MVC task. During the dorsiflexion tasks, the torques generated in both the 10 and 50% MVC tasks did not differ pre-, in- and post-flight. TA EMG amplitudes were significantly higher in- than pre-flight for both the 10 or 50% MVC tasks, and remained elevated post-flight for the 50% MVC test. Both the Sol and MG EMG amplitudes were significantly higher in-flight than either pre- or post-flight for both the 10 and 50% MVC tests. These data suggest that the most consistent response to space flight was an elevation in the level of contractions of agonists and antagonists when attempting to maintain constant torques at a given level of MVC. Also, the chronic levels of EMG activity in selected ankle flexor and extensor muscles during space flight and during routine activities on Earth were recorded. Compared with pre- and post-flight values, there was a marked increase in the total EMG activity of the TA and the Sol and no change in the MG EMG activity in-flight. These data indicate that space flight, as occurs on shuttle missions, is a model of elevated activation of both flexor and extensor muscles, probably reflecting the effects of programmed work schedules in flight rather than a direct effect of microgravity.

Adaptation, Physiological↗

Psychiatric interview and psychometric predictors of cardiac transplant survival.

OBJECTIVE: This study prospectively investigated the relation between pretransplant assessment of psychiatric diagnosis, coping skills, and social support and outcome measures of survival and health care utilization. METHOD: Ninety-four heart transplant patients underwent structured interviews and completed a battery of self-report psychometric tests assessing coping style, health status, and psychosocial supports. Follow-up that ranged from 9 to 56 months after transplant produced a group of 63 survivors and 31 nonsurvivors, who were found to be comparable in terms of pretransplant cardiac status and severity of illness. RESULTS: Survival analysis showed that dimensional psychometric measures of coping and social support based on patient self-assessment were the best significant predictors of survival. Considered separately, interview-determined ratings of social support and pretransplant compliance with treatment regimens were also potential predictors. Formal DSM-III-R diagnoses were related specifically to posttransplant hospital utilization (axis I diagnoses) and posttransplant health behavior (axis II diagnoses). CONCLUSIONS: The data demonstrate the value of multifaceted assessment, since psychiatric diagnosis, coping style, and psychosocial support may contribute differently to prediction of such aspects of outcome as mortality and health care utilization.

Adaptation, Psychological↗

Evaluation of antibodies elicited by immunization with pertussis toxin.

The monoclonal antibody termed 1B7 neutralizes pertussis toxin in vivo in cell culture systems and can also passively protect mice from a challenge with live Bordetella pertussis (9). It has been suggested that most other independently derived neutralizing monoclonal antibodies recognizing the S1 subunit apparently recognize the same epitope as 1B7, and that the S1 subunit contains only one immunodominant protective epitope (1). These antibodies have been termed Class A antibodies (8) and inhibit the ADP-ribosyltransferase but not the NAD glycohydrolase activity of the toxin (7). We are testing the hypothesis that immunization with inactivated preparations of pertussis toxin that lead to protection are associated with the production of Class A antibodies. If true, then identification of Class A antibodies in sera might provide a serological correlate of protection. If false, then development of assays designed to detect the important protective antibodies are necessary. Our initial results suggest that Class A antibodies are not the predominant neutralizing antibody in mice immunized with vaccines containing formalin-treated pertussis toxin.

Animals↗

Self-report evaluation of health behavior, stress vulnerability, and medical outcome of heart transplant recipients.

OBJECTIVE: The purpose of this study was to explore the value of patient self-report assessment in heart transplant candidacy evaluation, utilizing the Millon Behavioral Health Inventory (MBHI). Patient's MBHI measures were related to important pretransplant patient characteristics and posttransplant measures of health behavior, medical morbidity, and mortality. METHOD: Ninety heart patients with end-stage cardiac disease completed the MBHI during pretransplant candidacy evaluations, and also were interviewed concerning their coping effectiveness, support resources, and compliance history. Postransplant follow-up of 61 living and 29 deceased patients included measures of survival time, postsurgical medical care, rejection and infection episodes, and nurse ratings of medication compliance and problematic interpersonal health behaviors. RESULTS: The MBHI coping scales were found to significantly discriminate good and poor pretransplant compliance, and interview judgments of good and poor coping and support resources, with modest accuracy. The MBHI also was superior to these interview judgments in predicting posttransplant survival time and medical care used. Certain scales were also positively associated with physical parameters of pretransplant and posttransplant status. CONCLUSIONS: Patient self-report with the MBHI can contribute to identification of patients at risk for a problematic outcome with transplant, by providing information pertinent to clinical decision making and outcome management analysis with this special population of cardiac patients.

Adult↗