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Biomedical subjects

L Tucker

Publications and source records attributed to L Tucker.

At least 19 recordsLinked to original sources

Specialized extended hospital treatment for borderline patients.

The intensive psychoanalytically oriented hospital treatment described by the authors was developed specifically for borderline patients. This unique treatment, an integrated multimodal approach, is based on the theory that the disturbed behaviors and relationships of borderline patients are manifestations of intrapsychic impairment. The authors use a detailed case report to illustrate how the theory is transformed into technical precepts and applied to all aspects of the treatment.

Activities of Daily Living

Independent analysis of the 16/6 idiotype lupus model. A role for an environmental factor?

The recent description of a lupus-like disease in normal mice after injections of human mAb that bind DNA and carry the common Id 16/6 Id has excited much attention. In an effort to reproduce this model we have performed two experiments using eight human mAb three of which bear the 16/6 Id. Despite using an injection protocol very similar to that of the original authors and waiting for up to 1 yr we were unable to detect any autoantibodies or any evidence of renal disease. We suspect that our failure to reproduce the model may be due to differences in either or both the batches of CFA used, or in the animal house environments. It supports the view that a mosaic of effects is required to induce clinical expression of an autoimmune disease.

Animals

Interaction of intact type VI collagen with hyaluronan.

The capacity of non-pepsinyzed type VI collagen to bind to hyaluronan was investigated. Type VI collagen was extracted from bovine meniscal cartilage with 6 M GuHCl and purified by extraction of PEG precipitates and dissociative Sephacryl S-500 HR chromatography. Type VI collagen, detected with a monoclonal antibody, bound in 0.5 M NaCl to hyaluronan-coated micro-wells, the degree of binding being higher at 37 degrees C than 23 degrees C and 4 degrees C. Incubation of type VI collagen in competitive inhibition assays with testicular hyaluronidase digests of hyaluronan in liquid phase, reduced binding of the protein to hyaluronan-coated microwells to background levels. Thus, non-pepsinyzed type VI collagen binds to hyaluronan in vitro.

Animals

Molecular analysis of a germ line-encoded idiotypic marker of pathogenic human lupus autoantibodies.

Id-16/6 is an idiotypic marker found in both IgM and IgG antibodies, as well as in the tissue lesions of patients with SLE. The prototypic Id-16/6+ mAb is 18/2, whose VH3-derived H chain is encoded by an unmutated germ-line gene. We found that the H chains of VH3-derived Id-16/6+ antibodies contain the major determinants of Id-16/6. Moreover, B cell clones from which those antibodies were harvested produce RNA that hybridized under conditions of high stringency to oligonucleotide probes corresponding to the CDR of the VH segment of 18/2. Western blots of Id-16/6+ mAbs with anti-Id confirmed the association of the Id with H chains. Id-16/6 can identify a subgroup of VH3-derived antibodies we have termed the 18/2 CDR family. However, Id-16/6 can also be expressed in some antibodies unrelated to the 18/2 CDR family. No characteristic Ag-binding specificity was found among the members of the 18/2 CDR family. The principal phenotypic feature shared by all known members of the family is Id-16/6.

Amino Acid Sequence

Individual VH genes detected with oligonucleotide probes from the complementarity-determining regions.

The germ-line and expressed Ig repertoire was examined with three oligonucleotide probes from the CDR regions of VH18/2, a VH gene from the largest human VH gene family, VHIII. Each oligonucleotide probe detected small numbers of germ-line bands (1-5) under conditions in which single base differences can be detected; more than half of these bands were polymorphic. The combined results from pairs of oligonucleotides from CDR1 and CDR2 identified a single band on Southern blots, as did a probe from the 5' end of CDR2. This band contains the 18/2 germ-line gene. The nucleotide sequence of expressed VH genes that hybridized to both CDR probes or to the 5' CDR2 probe were greater than or equal to 97% homologous to 18/2 in both the framework and CDR regions. This group of closely related VH genes, the 18/2 CDR family, appears to be overexpressed. The role of polymorphisms and differential expression of individual V genes in multigenic autoimmune diseases, as well as the organization and expression of individual V genes, can be examined with pairs of oligonucleotides from CDR1 and the 3' end of CDR2, or with probes from the 5' end of CDR2.

Amino Acid Sequence

Relationships among measures of alcohol drinking behavior, life-events and perceived stress.

Two measures of stress (life-events and perceived stress) and a measure of alcohol-drinking behavior were administered to 6,747 adult males. Analysis was carried out to examine the extent to which subjects classified into drinking-behavior groups differed on stress measures while controlling for age, income, and race. Significant differences held up under age, race, and income controls for life-events and perceived stress between the abstinence, common-use, and problem-drinking groups. Stress scores increased sequentially across the drinking-behavior groups. Apparently, men who are life-long abstainers (teetotallers) experience fewer life-events and perceive less stress than moderate drinkers, while moderate drinkers experience less stress than heavy drinkers.

Adaptation, Psychological

Effects of some metabolites of pyritinol (Encephabol) on ACH release from brain slices.

The K+ stimulated release of radioactively labelled ACH from cortical slices obtained from rats was increased by some pyridine derivatives that are metabolites of pyritinol. It appears that this effect is not mediated by an interaction with cholinergic receptors but may be related to the lipid solubility of the compounds. It is suggested that an effect of these metabolites on the membrane of nerve endings may be part of the mechanism by which pyritinol treatment increases ACH levels and release in old rats.

Acetylcholine

Long-term hospital treatment of borderline patients: a descriptive outcome study.

The authors report a prospective 2-year outcome study of 40 inpatients with severe personality disorders who were treated on a specialized long-term unit for patients with "borderline conditions." Treatment goals included improving interpersonal relationships and facilitating a lasting discharge from the hospital. Data were collected at admission, discharge, and 1 and 2 years after discharge. The data reflect change from admission to follow-up in impulsivity, psychotherapy, and social adjustment. Mediating effects of length of stay on outcome are discussed.

Adolescent

Autonomic interactions in the aging heart: age-associated decrease in muscarinic cholinergic receptor mediated inhibition of beta-adrenergic activation of adenylate cyclase.

The ability of the muscarinic receptor agonist, carbachol, to inhibit beta-adrenergic activation of adenylate cyclase was examined in cardiac membranes from 6-month (young adult) and 24-month (aged) old rats in an effort to assess the effect of aging on adrenergic-cholinergic interactions in the heart. At varying concentrations (0.1-100 microM) of carbachol, GTP plus isoproterenol-stimulated adenylate cyclase activity was inhibited 5-39% in cardiac membranes from 6-month-old rats; this inhibition was statistically significant at all but the lowest concentration (0.1 microM) of carbachol used. In contrast, in cardiac membranes from 24-month-old rats, the inhibition of GTP plus isoproterenol-stimulated adenylate cyclase activity by carbachol was very weak (3-20% with 0.1-100 microM carbachol), and statistically insignificant. The muscarinic receptor antagonist, atropine, blocked the inhibition of GTP plus isoproterenol-stimulated enzyme activity by carbachol showing that the observed inhibitory effect of carbachol was muscarinic receptor dependent. The basal adenylate cyclase activity (which showed no significant age-related difference) was unaffected by carbachol. No significant age-related differences were evident in: (a) the concentration of carbachol required for half-maximal inhibition of GTP plus isoproterenol-stimulated adenylate cyclase activity; (b) the density of muscarinic receptor sites; and (c) their agonist and antagonist binding affinities. The GTP plus isoproterenol-stimulated cyclase activity measured in the absence of carbachol was approximately 70% lower in cardiac membranes from 24-month-old, compared to 6-month-old rats, confirming an age-associated decline in beta-adrenergic activation of the cyclase observed in our previous study [Mech. Ageing Dev., 19: (1982) 127-139]. The above findings suggest an apparent age-related decline in the postsynaptic antiadrenergic action of cholinergic stimulus in the heart; thus, exaggerated cholinergic antagonism of beta-adrenergic stimulus does not seem to contribute to the impaired adrenergic control of the heart in aging. On the other hand, autonomic imbalance, due to excessive weakening of the antiadrenergic influence of cholinergic stimulus, may compromise the ability of the cholinergic system to counteract the tendency of unrestrained adrenergic drive to increase ventricular vulnerability to fibrillation; this, in turn, may favor the high incidence of cardiac arrhythmias in aging.

Adenylyl Cyclases

Felodipine as a replacement for minoxidil in the treatment of severe hypertension.

The new calcium antagonist felodipine has been compared with minoxidil in the management of severe hypertension in a group of 17 men. Satisfactory control of blood pressure was achieved in all patients with a combination of beta blocker, loop diuretic and minoxidil after inadequate control on a standard regimen of beta blocker, thiazide and vasodilator. The optimal dose of felodipine was titrated after a placebo phase. In a double blind crossover trial blood pressure on felodipine (150/88 +/- 19/8 mmHg, SD) was the same as on minoxidil (148/87 +/- 23/11 mmHg, NS) and the postural difference was similar (NS) on both drug regimens. Body weight was lower on the felodipine regimen (P less than 0.01), as was supine heart rate (P less than 0.05). There was a small rise in plasma liver enzymes on felodipine therapy (P less than 0.01). Felodipine was well tolerated and may be useful in the management of severe hypertension.

Aged

Felodipine can replace minoxidil in the treatment of refractory hypertension.

In a group of 15 men with severe hypertension in a double-blind crossover trial, the new calcium antagonist felodipine has been shown to lower blood pressure as effectively as minoxidil when used in combination with a beta-blocker and a loop diuretic. Felodipine was well tolerated and may have a role in the management of severe hypertension.

Aged