Behavioral treatment of isolated systolic hypertension in the elderly

Fifteen hypertensive patients were recruited from a geriatric medicine clinic for a research project designed to evaluate a Behavioral Stepped-Care treatment program of high blood pressure (HBP). All patients met the selection criteria of the Isolated Systolic Hypertension (ISH) in the Elderly (SHEP) clinical trial. During baseline, subjects recorded BP at home 9 times/day (3 times each, shortly after awakening, during the middle of the day, and within an hour of retiring) for 1 month and mailed that data to us daily. In addition, they came to the clinic weekly and had their BP recorded by a nurse. During treatment 1, systolic (SBP) feedback, they were trained to lower SBP at home using their sphygmomanometers. They also continued to monitor BP and to obtain weekly professional BP readings. During treatment 2 (relaxation), they were trained to relax; they followed the self-administration and data-collection protocol as in treatment 1. Each treatment phase lasted 3 months. Average monthly self-determined BP fell significantly from 166.4/85.8 (SBP/DBP) mm Hg during baseline to 153.3/81.2 by the end of the relaxation phase; average monthly professionally measured BP fell significantly, from 164.7/87.1 to 156.9/81.5. These findings show that a nurse-supervised, patient-administered behavioral treatment program of ISH can yield sustained, significant falls in BP.Ms. Pearce and Dr. Burton were supported in part by the Johns Hopkins Academic Nursing Home Award, PO, AG04402, from the National Institute on Aging. This material was presented in part at the annual meeting of the Gerontological Society of America, November 1988, San Francisco.     

Short- and Long-Term Alterations of Gene Expression in Limbic Structures by Repeated Electroconvulsive-Induced Seizures

Rats were submitted to a series of 10 daily electroconvulsive shocks (ECS). A first group of animals was killed 1 day after the last seizure and a second group 30 days later. Tyrosine hydroxylase (TH) activity was measured using an in vitro assay in the nucleus caudatus, anterior cortex, amygdala, substantia nigra, ventral tegmental area, and locus ceruleus. The mRNA corresponding to this enzyme (TH-mRNA) was evaluated using a cDNA probe at the cellular level in the ventral tegmental area, substantia nigra, and locus ceruleus. Met-enkephalin (MET)-immunoreactivity and the mRNA coding for the preproenkephalin (PPE-mRNA) were assayed in striatum and the central nucleus of the amygdala. The day after the last ECS an increase of TH activity was observed in the ventral tegmental area, locus ceruleus, and substantia nigra in parallel with a similar increase in the amygdala and striatum; in the anterior cortex TH activity remained unchanged. TH-mRNA was increased in the locus ceruleus, evidencing the presence in this structure of a genomic activation. The amounts of MET and PPE-mRNA were unaffected in the striatum but increased in the amygdala. Thirty days after the last ECS we observed a decrease of TH activity in the amygdala and of TH-mRNA amount in the ventral tegmental area. In the locus ceruleus TH-mRNA remained higher in treated animals than in controls whereas TH activity returned to control levels. These results demonstrate that a series of ECS induces an initial increase of the activity of mesoamygdaloid catecholaminergic neurons followed by a sustained decrease through alterations of TH gene expression which could mediate the clinical effect of the treatment.     

Age differences in responsiveness of brainstem chemosensitive neurons to extracellular pH changes

The sensitivity of neurons in the caudal chemosensitive area on the ventrolateral surface of the medulla oblongata (VMS) to extracellular pH changes was examined in newborn and young developing kittens and compared to that of adult cats. The pH was varied by superfusion of the VMS with mock cerebrospinal fluid (CSF) of pH 7.4 (control), 7.0 (acid) and 7.8 (alkaline). A total of 97 neuronal units in the three age groups changed their firing rates inversely in response to extracellular fluid (ECF) pH changes. The greatest sensitivity was found in the adult group where acid superfusion caused an increase in neuronal activity. The least sensitivity was observed in the newborn group (1-6 days old), whereas the young kitten group (4-6 weeks old) exhibited an intermediate sensitivity. Neurons of kittens older than 7 weeks of age demonstrated a response pattern characteristic of the adult group. Neurons of neonates older than seven days, exhibited a response pattern characteristic of the young kitten group.     

Peripheral T-lymphocyte activation by human T-cell leukemia virus type I interferes with the CD2 but not with the CD3/TCR pathway

Human T-cell leukemia virus type I (HTLV-I) is etiologically associated with adult T-cell leukemia, an aggressive lymphoproliferative disorder, and with chronic neurological diseases. In vitro it can infect several types of cells but transforms only human T lymphocytes. We have previously shown that HTLV-I viral particles, even when noninfectious, were able to activate human resting T lymphocytes, suggesting that this activation step may be important in the initiation of the lymphoproliferative process. In the present study, we first demonstrate that in contrast to other mitogenic stimuli, HTLV-I has the unique property to activate human resting T cells in the absence of accessory cells. We then investigate the relationship between HTLV-I-induced T-cell activation and the classical well-known pathways of activation, namely, the CD3/TCR and CD2 pathways. Competitive blocking experiments were performed in which the effects of monoclonal antibodies (MAb) to the CD3/TCR complex or to the CD2 molecule were evaluated on the HTLV-I activation of T cells and compared with that obtained on phytohemagglutinin (PHA)-stimulated cells. It was found that anti-CD3 or -TCR MAb strongly suppress the proliferative response of T cells to PHA, but are significantly less efficient in inhibiting the activation initiated by HTLV-I. By contrast, MAb recognizing specific epitopes of the CD2 molecule inhibit the proliferative response of T cells to PHA or to HTLV-I to the same extent. The results provide evidence that HTLV-I virions interfere mainly with activation via CD2 but not via the CD3/TCR complex. Considering the earlier expression of the CD2 molecule on human T-cell precursors, these observations might be relevant to the characterization of the differentiation stage at which viral infection could interfere with the development and the maturation of T lymphocytes.     

Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma.

The action of retinoids on gene regulation is mediated by three distinct nuclear retinoic acid receptor (RAR) subtypes called RAR alpha, beta and gamma. Since RAR gamma is predominantly expressed in adult skin, specific ligands for this subtype could (i) represent valuable tools to evaluate the biological role of RAR gamma in skin and (ii) provide therapeutic entities with a higher therapeutic index at lower teratogenic risk. Using in vitro binding studies and a functional transactivation assay, we have identified three compounds with high RAR gamma selectivity.     

Functional analysis of a complex oncogene arrangement in biotype III Agrobacterium tumefaciens strains

The ubiquitous grapevine-associated octopine/cucumopine Ti plasmids of biotype III Agrobacterium tumefaciens strains carry two T regions, TA and TB, with a complex oncogene arrangement. Within the octopine/cucumopine group, two main strain types were identified: large TA strains with a TA region resembling the TL region of the biotype I octopine strain Ach5 and small TA strains with a similar T region organization as the large TA strains but with a large internal TA deletion. Structural and functional studies of the representative large TA strain Tm4 revealed six oncogenes. Each oncogene was inserted in a disarmed vector and tested for biological activity using the corresponding oncogenes of Ach5 as standards. Five Tm4 oncogenes, TA-iaaM, T-ipt, T-6b, TB-iaaH and TB-iaaM, were shown to be active, the IS-interrupted TA-iaaH gene was inactive. To study the role of each gene in the pTiTm4 context, several single and multiple pTiTm4 mutations were constructed. It was shown that whereas TA-iaaM and TB-iaaH are essential for tumour formation on grapevine, T-ipt, T-6b and TB-iaaM are not. The avirulence of the TA-iaaM ^- mutant was shown to be due to an inhibitory effect of the T-ipt gene, since a TA-iaaM ^- /T-ipt ^- double mutant was fully virulent. We conclude that the TA-iaaM gene of large TA strains is specifically required to counteract the tumour growth inhibiting activity of the T-ipt gene. Both TA-iaaM and T-ipt are absent from the small TA strains. A model on the roles and interactions of the different oncogenes in large TA and small TA strains is presented.