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Biomedical subjects

K Tate

Publications and source records attributed to K Tate.

12 recordsLinked to original sources

Induction of a pharmacologically active clonotypic B cell response directed to an immunogenic region of the human beta 2-adrenergic receptor.

It has been reported that autoantibodies against the beta 2-adrenergic receptors are involved in the pathology of allergic disorders and of Chagas' disease. Therefore, the immune response against a peptide (H26Q) corresponding to the putative second extracellular loop of the human beta 2-adrenergic receptor, which could be a target for autoantibody attack, was analysed in view of its possible immunogenicity. The free peptide induced a T cell-mediated humoral response in the context of three different murine MHC haplotypes. The T cell epitope was found to be localized in the N-terminal region of the peptide. Highly specific T helper cells were capable of stimulating B cells with the potential to generate a large antibody repertoire reactive with the loop peptide. MoAbs were screened to analyse this B cell response for antibodies potentially interfering with receptor function and a MoAb was found that impaired ligand binding to the receptor.

Animals

Bronchopulmonary lavage for pulmonary alveolar proteinosis.

In summary, total-lung bronchopulmonary lavage was performed five times on two patients under general anesthesia with controlled ventilation using a Robert-Shaw double lumen ETT. One lavage was complicated by a hydrothorax that was treated without untoward sequelae. No significant hypoxemia, circulatory impairment or leakage of lavaged fluid into the opposite lung was noted on any occasion. The average time of all procedures was 108 minutes (range 80-150 minutes), and patients were extubated on all occasions 2 to 5 hours after the treatment. Patients were discharged 24 to 36 hours after the last lavage with improvement, though not resolution, of the alveolar infiltrates radiographically. The ABG analysis revealed minimal improvement in oxygenation in Case No.1 from a preoperative paO2 of 60 mmHg on room air to a paO2 of 74 mmHg on the day of discharge. However, the patient was able to resume his normal activity level. In Case No.2, the patient's resting paO2 did not improve significantly from the preoperative value of 82 mmHg. Subjectively, however, the patient noted marked improvement. Prior to bronchopulmonary lavage, this patient's SaO2 decreased from 97% to 81% after walking 800 feet. Approximately a week and a half after discharge, the patient reported being able to run without symptoms and generally was feeling well. With careful attention to detail and the coordination of resources from the departments of anesthesia, pulmonary medicine, respiratory therapy and nursing services, bronchopulmonary lavage can be performed safely and efficiently in order to curtail the progressive hypoxemia which often develops in patients with PAP.

Adult

Haplotype specific homology scanning algorithm to predict T-cell epitopes from protein sequences.

We present a homology scanning microcomputer program to predict functional T-cell epitopes within proteins. By taking into account particular human or mouse restriction elements the predictions are made haplotype-specific. The generality of this approach is confirmed by (i) identification of well-characterized immunogenic T-cell determinants in lysozyme (ii) search for potential T epitopes on unanalysed proteins like the human beta 2-adrenoreceptor (iii) modification of non-immunogenic peptide sequences in order to generate T-cell determinants.

Algorithms

Mortality in a large southeastern facility for persons with mental retardation.

Mortality rates for institutionalized persons with mental retardation were presented. Rates were provided for two time intervals, 1974 through 1979 and 1980 through 1985, and by age, race, and gender. Consistent differences between black and white residents or by gender were not indicated. However, significant improvement in mortality did occur between the two time periods. Persons with profound retardation were found to have higher mortality than those whose retardation was mild to severe. Respiratory disease was the most prevalent cause of death among the individuals with profound mental retardation, whereas heart disease and cancer were the most common causes of death among persons with mild, moderate, or severe retardation. Aging of the population was noted over the period of the study, indicative of the increasing frailty of the institutionalized population.

Adolescent

Molecular characterization of the human beta 3-adrenergic receptor.

Since the classification of beta-adrenergic receptors (beta-ARs) into beta 1 and beta 2 subtypes, additional beta-ARs have been implicated in the control of various metabolic processes by catecholamines. A human gene has been isolated that encodes a third beta-AR, here referred to as the "beta 3-adrenergic receptor." Exposure of eukaryotic cells transfected with this gene to adrenaline or noradrenaline promotes the accumulation of adenosine 3',5'-monophosphate; only 2 of 11 classical beta-AR blockers efficiently inhibited this effect, whereas two others behaved as beta 3-AR agonists. The potency order of beta-AR agonists for the beta 3-AR correlates with their rank order for stimulating various metabolic processes in tissues where atypical adrenergic sites are thought to exist. In particular, novel beta-AR agonists having high thermogenic, antiobesity, and antidiabetic activities in animal models are among the most potent stimulators of the beta 3-AR.

Adrenergic beta-Agonists

The influence of carbohydrate structure on the clearance of recombinant tissue-type plasminogen activator.

Modification of the carbohydrate structures of recombinant tissue-type plasminogen activator (rt-PA) can increase or decrease its rate of clearance in rabbits. When rt-PA was treated with sodium periodate to oxidize carbohydrate residues, the rate of clearance was decreased from 9.6 +/- 1.9 ml min-1 kg-1 to 3.5 +/- 0.6 ml min-1 kg-1 (mean +/- SD, n = 5). A similar change in the clearance of rt-PA was introduced by the use of endo-beta-N-acetyl-glucosaminidase H (Endo-H), which selectively removes high mannose asparagine-linked oligosaccharides; the clearance of Endo-H-treated rt-PA was 5.0 +/- 0.5 ml min-1 kg-1. A mutant of rt-PA was produced with an amino acid substitution at position 117 (Asn replaced with Gln) to remove a potential glycosylation site that normally contains a high mannose structure. The clearance of this material was also decreased, similar to the periodate and Endo-H-treated rt-PA. Conversely, when rt-PA was produced in the CHO 15B cell line, which can produce only high mannose oligosaccharide structures on glycoproteins, the clearance was increased by a factor of 1.8. These results demonstrate that the removal of rt-PA from the blood depends significantly upon the nature of its oligosaccharide structures.

Animals

A technique for transfer of patients to a fracture table.

A simple method of transfer of patients from a surgical transport trolley to a fracture table, using a modified canvas stretcher, is described. It is believed that this technique offers increased safety to the patients and the hospital personnel.

Equipment Design