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Biomedical subjects

C Gomez

Publications and source records attributed to C Gomez.

At least 19 recordsLinked to original sources

Cross-species reactivity of the anti-idiotype anti-OKT3 cascade between mice and humans.

The administration of murine mAb specific for the CD3 epsilon subunit of the TCR complex (OKT3) has been demonstrated to engender in humans an anti-OKT3 idiotypic cascade. This study used murine-derived anti-OKT3 (Ab2) as a bioreagent to determine whether this Ab2 and polyclonal anti-(anti-OKT3) (Ab3) generated in some human kidney transplant patients are idiotypically connected. Two anti-OKT3 mAbs G-880 (IgG1) and M-12 (IgM) were derived by immunizing BALB/c mice with the OKT3-secreting hybridoma. The two mAbs exhibited specificity for OKT3 F(ab)'2 idiotypic determinants. Both mAbs were tested for their ability to inhibit OKT3 induced mitogenesis and to block FITC-OKT3 binding to cell surface CD3 epsilon chain. The M-12 mAb inhibited OKT3-induced mitogenesis and blocked (approximately 60%) the binding of OKT3 to peripheral blood (PBL) T-cell CD3 epsilon chain in flow cytometry. In contrast, the G-880 mAb did not inhibit mitogenesis and only weakly blocked OKT3 binding to CD3 epsilon chain (approximately 12%). Sera of kidney transplant recipients who received OKT3 antirejection therapy and who developed antiidiotypic anti-OKT3 antibodies could be divided into two subgroups exhibiting anti-OKT3 activity: (a) those who had similar specificity as M-12 and failed to enhance the M-12 inhibition of OKT3 binding to PBL T-cell CD3 epsilon chain when added as a third component (n = 3), and (b) those with anti-OKT3 antibodies with idiotype specificity dissimilar to M-12 and who were able to increase the (maximum 60%) inhibition obtained with M-12 in the OKT3 to T-cell CD3-binding assay (n = 4). From these observations, we conclude that M-12 had the characteristics of an Ab2 beta and G-880 that of an Ab2 alpha. Additionally, there was an idiotypic connectivity of mouse-derived M-12 anti-OKT3 (Ab2) and OKT3-engendered human polyclonal anti-(anti-OKT3) (Ab3), in that three of seven patients examined had human serum IgG antibodies that specifically recognized M-12 idiotypic determinants as demonstrated in ELISA.

Animals

Laterality, alternation, and perseveration relationships on the T-maze test.

The T-maze test has been used to study several entirely different issues: spontaneous alternation behavior (SAB), perseveration behavior (PB), and behavioral lateralization. Despite the fact that in this test the behavior studied is always the same one (i.e., side choice), the possible relationships among SAB, PB, and lateralization have not been previously evaluated. The present study investigated the relationships among these functions. The results demonstrated that (a) shock increases PB and lateralization but decreases SAB, (b) practice increases lateralization and decreases SAB but does not modify PB, and (c) there are sex differences for alternation and SAB. Because these functions are expressed by the same behavioral pattern, they must be quantified simultaneously to avoid mistaken conclusions when the T-maze test is used.

Animals

[Paraneoplastic encephalomyelitis and Lambert-Eaton syndrome].

In two men presenting with muscle weakness and disturbances of equilibrium neurophysiological examination by repeated stimulations revealed responses suggestive of Lambert-Eaton syndrome. In the first month of the disease very high levels of anti-Hu antibody were found in the serum and CSF, betraying a malignant lesion. This was confirmed by autopsy 4 months later in one patient and by bronchial biopsy 16 months later in the other patient. Both had small-cell lung carcinoma associated with paraneoplastic encephalomyelitis.

Aged

Assessment of antigenic determinants for the human T cell response against myelin basic protein using overlapping synthetic peptides.

Immunization of experimental animals with myelin basic protein (MBP) or with specific MBP encephalitogenic determinants induces an autoimmune central nervous system (CNS) disease, experimental allergic encephalomyelitis, often studied as a model for human demyelinating disorders. This study examines the antigenic determinants of MBP recognized by human T cells using overlapping, synthetic peptides and T cell lines and clones isolated from four HLA-typed, neurologically normal subjects. T cell lines and clones isolated from individual subjects recognized at least one and as many as five distinct T cell determinants. In some instances the peptides recognized included determinants previously shown to induce experimental allergic encephalomyelitis (EAE) in experimental animals. In this group of four subjects, some determinants of MBP, including residues 5-25, 35-47, 65-75, and 81-100, were recognized by T cells derived from more than one individual suggesting that these regions may be particularly immunogenic for humans.

Antigen-Presenting Cells

Factors affecting the ten-year outcome of human renal allografts. The effect of viral infections.

Long-term (10-year) results of kidney transplantation have been analyzed from this center with respect to several variables. In this report the influence of viral disease was added in studying the effect of cadaver versus living-related donor, recipient race, and compliance. Over all, 10-year actuarial patient and graft survival were 68% and 48%, respectively. Cytomegalovirus, hepatitis B and C, and HIV-1 were studied for their effects, and survival curves analyzed statistically. Although cadaver and living-related donor, recipient race, and compliance were 3 main variables influencing graft survival, these 4 viruses were not selective in their effects on any of them. Hepatitis B surface antigen positivity and hepatitis C antibody positivity did not influence overall mortality or graft survival. Only cytomegalovirus seronegative status was important (as opposed to seropositive status, which was not). Of seronegative patients only those receiving a kidney from a seropositive donor were adversely affected. The presence of HIV-1 antibody had an adverse effect on graft survival, but the question remains as to whether overall mortality in HIV seropositive patients is any worse than those receiving dialysis therapy.

Cadaver

Differential memory and executive functions in demented patients with Parkinson's and Alzheimer's disease.

Selected aspects of verbal memory and executive function were compared in 11 demented Parkinson's disease (PD) patients and 11 Alzheimer's disease (AD) patients with equally severe dementia, with 11 healthy controls matched for age and education. Semantic and episodic memory were impared in all patients compared with controls, but to a relatively greater degree in AD patients than in those with PD. In contrast, demented PD patients were relatively more compromised on executive tasks. These findings, taken in the context of the neuropathological and neurochemical overlap between demented PD and AD patients, suggest that differences in neurobehavioural patterns in patients with these diseases are relative, rather than absolute.

Aged

Frontal lobe function in progressive supranuclear palsy.

Performance on tasks evaluating "executive and attentional" processes presumably subserved by prefrontal cortex were compared in patients with progressive supranuclear palsy and with age- and education-matched control subjects. The results indicated that patients with progressive supranuclear palsy were particularly impaired when a task required sequential movements, conceptual shifting, monitoring the frequency with which stimuli are presented, or rapid retrieval of verbal knowledge. These deficits could not simply be accounted for by slowed information processing or by a deficit in representational knowledge. Conceivably, "weak activation" of frontal lobe representational knowledge characterized by an observed attentional deficit results in the neuropsychological impairments noted in patients with progressive supranuclear palsy. The oral administration of physostigmine, under double-blind placebo-controlled conditions, did not facilitate executive or attentional performance as evaluated by our tasks.

Affect

Memory impairment in patients with progressive supranuclear palsy.

Verbal memory was compared in 12 patients with progressive supranuclear palsy and 12 healthy control subjects matched for age, sex, and education. Learning, consolidation, and retrieval were significantly impaired in patients with progressive supranuclear palsy. Information scanning, which requires the use of short-term memory processes, remained intact. Duration of symptoms and degree of motor dysfunction correlated with intrusions during learning. No relation between central dopamine metabolism and memory dysfunction could be established.

Aged

Physostigmine treatment of progressive supranuclear palsy.

Cognitive and extrapyramidal effects of cholinomimetic therapy were evaluated in 8 patients with progressive supranuclear palsy. Each was randomized to a 10-day double-blind crossover trial of physostigmine and placebo. Physostigmine treatment was associated with marginal and inconsistent changes in long-term memory, suggesting that cholinergic therapy alone is insufficient to restore cognitive function. Motor scores remained unchanged.

Aged

Evaluation of pediatric cadaver kidneys transplanted into adult recipients receiving cyclosporine.

The major problem in clinical transplantation is the imbalance between the need for cadaveric organs and the available numbers of donors. If pediatric kidneys were transplanted into adult recipients when no pediatric recipient was available, the potential number of renal donors would be increased by 15 to 20%. Some centers are reluctant to use pediatric kidneys for adult recipients because of recent reports indicating poorer patient and allograft survival, increased delayed graft function, increased post-transplant hypertension and increased technical complication. (There also has been concern that the nephrotoxic effect of cyclosporine A would retard the organ growth that is necessary to provide normal renal function in adults.) A retrospective analysis was performed on 18 adult recipients who received kidneys from cadaver donors 14 months to 12 years old (group 1). These patients were compared to 106 adult recipients who received kidneys from donors greater than 12 years old (group 2). Actuarial patient survival at 1 year was 85% for group 1 and 95.8% for group 2 (p equals 0.13), while 1-year actuarial allograft survival was 83.1% for group 1 and 81.1% for group 2 (p equals 0.87). There was no significant difference between groups 1 and 2 in the frequency of delayed graft function, serum creatinine at 1, 3 and 6 months after transplantation, incidence of post-transplant hypertension or frequency of surgical complications. It is of interest that the pediatric kidneys had significant growth during the initial post-transplant month. Sonographic examination at postoperative days 1 and 30 demonstrated a mean increase in size from 80.7 to 143.5 cm. (p less than 0.001). In this series pediatric kidneys were safe and effective donor organs in adult recipients, and increased the available number of organs by 15%.

Adolescent

[Glossectomies].

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Adolescent

Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy.

Experimental allergic encephalomyelitis (EAE) is a paralytic autoimmune disease induced in susceptible animals by active immunization with myelin basic protein (MBP) or by passive transfer of MBP-specific T helper (TH) lymphocytes. We have analyzed the T cell receptor genes of 33 clonally distinct TH cells specific for a nonapeptide of MBP inducing EAE in B10.PL (H-2u) mice. All 33 TH cells used two alpha variable gene segments (V alpha 2.3, 61%; V alpha 4.2, 39%), the same alpha joining gene segment (J alpha 39), and two V beta and J beta gene segments (V beta 8.2-J beta 2.6, 79%; V beta 13-J beta 2.2, 21%). The anti-V beta 8 monoclonal antibody F23.1 was found to block completely recognition of the nonapeptide by V beta 8 TH cells in vitro and to reduce significantly the susceptibility of B10.PL mice to peptide-induced EAE.

Animals