Somatostatin receptor (SSTR) expression and function in normal and leukaemic T-cells. Evidence for selective effects on adhesion to extracellular matrix components via SSTR2 and/or 3.

We have examined normal T-cells and T-cell lines with respect to expression of various somatostatin receptor subtypes (SSTR1--5) using RT-PCR and PCR. To evaluate the function of these receptors we have further studied the effects of subtype specific signalling on T-cell adhesion using somatostatin analogs specific for various receptors as probes. Human T-lymphocytes showed SSTR expression related to activation and stage of differentiation. Normal T-cells (peripheral blood, T-cell clone) and T-leukaemia cell lines expressed SSTR2, SSTR3 and SSTR4. Normal T-cells expressed SSTR1 and SSTR5 while T-leukaemia lines did not. SSTR5 was selectively expressed in activated normal T-cells. T-lymphocytes produced no somatostatin themselves. Somatostatin and somatostatin analogs specific for SSTR2 and/or SSTR3 enhanced adhesion of T-cells to fibronectin (FN), and to a certain extent, also to collagen type IV (CIV) and laminin (LAM). T-lymphocytes express multiple SSTR and somatostatin may therefore regulate lymphocyte functions via distinct receptor subtypes as shown here for adhesion to extracellular matrix components (ECM) via SSTR2 and SSTR3. SSTR expression also distinguishes normal and leukaemic T-cells. Our findings suggest that SSTR subtypes may be useful targets for therapy during inflammatory diseases and malignancies affecting lymphocytes.

Expression and activity of matrix metalloproteases in human malignant mesothelioma cell lines.

The extracellular matrix metalloproteases (MMPs) secreted by various human tumor cells play a crucial role in tumor cell invasion and metastasis, but their expression in malignant mesothelioma (MM) cells has not been examined. In this study, we have investigated the spectrum of MMPs and tissue inhibitors of metalloproteases (TIMPs) produced by 8 MM cell lines. Using RT-PCR, we found that all investigated MM cell lines expressed genes encoding mRNA for MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-3 (stromelysin-1), MMP-9 (gelatinase B) and TIMPs 1, 2 and 3. We also found that 6/8 MM cell lines expressed MMP-7 (matrilysin) and 3/8 MM cell lines expressed MMP-10 (stromelysin-2). MMP-11 (stromelysin-3) was not detected in any of the MM cell lines. Production of MMP-2 and MMP-9 was confirmed using gelatin zymography. In addition, all MM cell lines secreted a 66 kDa metalloprotease, while 3/8 MM cell lines secreted 46, 48, 51 and 63 kDa metalloproteases which specifically degraded the extracellular matrix components fibronectin, vitronectin and laminin. The 66 kDa protease was identified as MMP-3 by Western blot. Our results reveal a broad spectrum of MMPs and TIMPs produced by MM cells and indicate that different substrate specificities of MMPs may play a role in MM cell invasion.

Defective chemokine production in T-leukemia cell lines and its possible functional role.

Peripheral blood lymphocytes and T-cell clones produced nanogram quantities of the chemokines RANTES, MIP-1alpha, MIP-1beta, MCP-1, IL-8 and GRO-alpha as well as the motogenic cytokine HGF. In contrast, various T-leukemia cell lines at different stages of differentiation did not produce the same chemokines/cytokines. In order to study the possible functional importance of the poor chemokine production different T-cell lines were compared with respect to development of motile forms and migration on extracellular matrix components in the absence and presence of various chemokines. RANTES, MIP-1alpha, MIP-1beta, IL-8, GRO-alpha and lymphotactin did not augment the development of motile forms including the size and appearance of the pseudopodia activity of the T-leukemia cell lines. The T-cell lines migrated spontaneously on/to fibronectin in a Boyden chamber assay system. Chemokines augmented the migration of the T-leukemia cell lines on fibronectin in the Boyden system in a chemotactic fashion with peak responses at 10 to 50 ng/ml. Thus, the production of chemokines is defective in neoplastic T-lymphocytes. The defective chemokine production does not seem to play any major role for the basic locomotor capacity of the cells but may modulate the responsiveness to exogenous chemokines.

Interaction of vasomotor and exocrine neurons in bullfrog paravertebral sympathetic ganglia.

A 2 min sample of an intracellular recording of in vivo synaptic activity from a vasomotor C-neuron in a bullfrog sympathetic ganglion was converted to a series of stimulus pulses. This physiologically derived activity was used to stimulate preganglionic C-fibres of similar ganglia studied in vitro. Intracellular recordings were made from exocrine B-cells within the ganglia. Although they do not receive fast, nicotinic synaptic input from preganglionic C-fibres, B-cell excitability was profoundly increased by stimulation of C-fibres with physiologically derived activity. Also, subthreshold depolarizing current pulses that failed to generate action potentials in B-cells under control conditions almost always generated action potentials whilst C-fibres were activated. These effects were attenuated or prevented by the luteinizing hormone releasing hormone antagonist, [D-pyro-Glu1,D-Phe2,D-Trp3,6]-LHRH (70 microM). The physiological release of luteinizing hormone releasing hormone from C-fibres therefore causes an interaction between vasomotor and exocrine outflow within a paravertebral sympathetic ganglion.

Infiltrative capacity of T leukemia cell lines: a distinct functional property coupled to expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1).

Infiltrative capacity was found to distinguish separate T leukemia cell lines. Of seven T-cell lines four exhibited capacity to infiltrate Matrigel. Analysis of infiltration was performed at the single-cell level throughout the Matrigel using a depth meter. Further, we examined differences in migration capacity and metalloproteinase production between infiltrating and non-infiltrating T-cell lines. The capacity to infiltrate was not directly correlated to the capacity to adhere to the Matrigel or to migrate on/to extracellular matrix components. It is concluded that infiltration capacity does not simply reflect capacity to migrate but represents a distinct functional property. The production of metalloproteinases and their inhibitors by the separate T-cell lines was analyzed using rt PCR, biosynthetic labelling, zymography, immunoprecipitation and ELISA. All T-cell lines with capacity to infiltrate produced matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) while non-infiltrating cell lines did not express MMP-9. Expression of MMP-1, 2, 3, 10, 14 and 17 showed no correlation to capacity to infiltrate. Analysis of infiltration in the presence of a metalloprotease inhibitor showed an increased number of cells within the gel. This enhancement of infiltration suggests that the function of MMPs and/or their inhibitors in lymphocyte infiltration is more complex than previously thought.

Stages of change profiles among incarcerated drug-using women.

This study investigated the utility and psychometric properties of the University of Rhode Island Change Assessment Scale (URICA) in a sample of 257 female inmates from a large urban prison. It addressed three major issues: (a) whether URICA captures stages of change among female offenders with a recent history of drug abuse; (b) whether distinct, reliable subgroup profiles would emerge from a cluster analysis of the URICA scale; and (c) whether women in these clusters would differ in their demographic characteristics, drug-use patterns, or psychological symptoms. Results indicate that the URICA is a useful, reliable, and valid tool to assess stages of change in drug-using incarcerated women. Consistent with other studies conducted with different populations, the scale yielded five distinct stages: precontemplation, contemplation, preparation, action, and maintenance. Cluster analysis using the hierarchical agglomerate method classified the subjects into five clusters, which correlated with subjects' psychological symptoms. Intervention implications of URICA are discussed.

On the role of muscarinic and peptidergic receptors in ganglionic transmission in bullfrogs in vivo.

Synaptic activity of individual B and C cells in the paravertebral sympathetic ganglia of urethan-anesthetized bullfrogs was monitored with intracellular electrodes. Postganglionic activity from the B and C fiber populations was monitored with suction electrodes. Intravenous infusion of muscarine (0.1 ml of 8 microM) excited individual B cells and increased the amplitude and rate of spontaneous, postganglionic B fiber population discharges. Muscarine also increased the number of action potentials (APs) within each burst of synaptic activity in individual C cells. Because atropine (0.1 ml of 0.1 microM) had little or no effect on postganglionic population B or C fiber activity, the muscarinic slow inhibitory postsynaptic potentials and slow excitatory postsynaptic potentials (EPSPs) are unlikely to be involved in the transmission, modulation, or integration of postganglionic outflow in vivo. Atropine did, however, decrease the number of APs per burst in individual C cells, an effect that could be explained if excitatory presynaptic muscarinic receptors exist on C fiber terminals. Stimulation of preganglionic C fibers at "physiological" frequencies evoked a lasting afterdischarge in postganglionic B fibers that was blocked by a combination of atropine and [D-pyro-Glu1,D-Phe2,D-Trp3,6]-luteinizing hormone-releasing hormone (LHRH). Release of LHRH from C fiber terminals and activation of the peptidergic, late-slow EPSP mechanism in B cells may therefore play a role in ganglionic transmission in vivo.

Correlates of crack abuse among drug-using incarcerated women: psychological trauma, social support, and coping behavior.

This investigation examines the relationship between psychological trauma and crack abuse among 158 women with a recent history of drug use who were incarcerated in a New York City jail facility. Interviewers obtained data on demographics, drug use, psychological trauma history, criminal history, social support, and coping behavior variables. Three-fourths of the total sample had used crack three or more times a week for a month in the past; a quarter had used other drugs, predominantly heroin, three or more times a week for a month in the past. Multiple logistic regression analysis was used to assess the association between adult psychological trauma variables (loss of custody of youngest child and lived in streets prior to arrest) and regular crack use in three sequential models. After adjusting for social support, coping behavior, demographics, and criminal history variables, women who had lost custody of their youngest child were 3.3 times more likely to be regular crack uses. Women who demonstrated more negative coping behavior and perceived themselves as having less emotional support were also more likely to be regular crack users. The association between childhood traumas (i.e., childhood sexual abuse, childhood physical abuse, parental alcohol abuse) and regular crack use was also assessed using multiple logistic regression; however, no significant associations were found between these childhood psychological traumas and regular crack use in both the unadjusted and adjusted models. Study findings underscore the importance of assessing environmental, interpersonal, and intrapersonal factors in tailoring treatment strategies for users of crack and other drugs.

In vivo activity of B- and C-neurones in the paravertebral sympathetic ganglia of the bullfrog.

1. Spontaneous, in vivo synaptic activity was recorded from 146 B-cells and 60 C-cells in the IXth and Xth paravertebral sympathetic ganglia of the urethane-anaesthetized bullfrog. Sympathetic outflow to the blood vessels, which are innervated by C-cells, is different from that received by targets in the skin, which are innervated by B-cells. 2. B-cells were divided into three groups: the first (61 cells) exhibited only action potentials (APs) at 0.01-0.3 s-1; the second (59 cells) exhibited APs and EPSPs and the third (26 cells) were silent. In addition to their usual suprathreshold input from the ipsilateral sympathetic chain, 53% of B-cells received subthreshold input which probably arose from fibres in the contralateral chain. 'Slow' B-cells exhibited less subthreshold activity and a slightly higher AP frequency than 'fast' B-cells. All B-cells are involved in a sympathetic reflex which is activated by tactile stimulation of the skin of the hindlimb. Activation of this reflex increased AP frequency without promoting long-lasting depolarization. 3. Sixty-seven per cent of C-cells exhibited rhythmic bursting activity with or without small intraburst EPSPs. Bursts tended to correlate with electrocardiographic (ECG) activity. The remainder exhibited an irregular pattern of activity which was not correlated with ECG activity and which included one to three APs and EPSPs interspersed between the bursts. Activity of both types of C-cell was inhibited following stimulation of the skin. 4. An average of twenty-three B-cells and twenty-one C-cells discharge simultaneously in vivo. This reflects branching of preganglionic fibres and results in synchrony of discharge in both postganglionic B- and C-fibres.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlates of problem drinking among drug-using incarcerated women.

The association between drug use--regular use of crack cocaine or heroin--and problem drinking was examined in a sample of 159 sentenced women at Rikers Island correction facility in New York City. Using logistic regression, this study tested the association between drug use and alcohol use, controlling for psychosocial variables (sexual abuse history, negative and positive coping skills, and depression), familial drug use (number of family members currently abusing drugs, and those currently abusing alcohol), and demographic variables and criminal history. The association between current, regular crack use and problem drinking approached significance in the final model, which adjusted for criminal behavior, demographic, familial abuse, and psychosocial variables. The results of this study point toward childhood sexual abuse, negative coping skills, and familial alcohol abuse as variables related to problem drinking among incarcerated women.

Sexual risk behavior of incarcerated, drug-using women, 1992.

In this study, sexual risk behavior of 104 incarcerated female drug users is examined. Findings demonstrate that incarcerated women who use drugs are at high risk for human immunodeficiency virus (HIV) infection because of their behavior prior to arrest. During the month prior to arrest, the majority of respondents were sexually active. Half reported past sexual contacts with injecting drug users, and more than one-third had traded sex for money or drugs. Consistent with other studies, condom use was more frequent with casual or commercial partners. Those who traded sex for money were less likely to be white Anglo or regular heroin users, and more likely to be regular crack users and alcoholic, have fathers who were drug or alcohol users, and perceive themselves as at-risk for contracting HIV and other sexually transmitted diseases.

Problem solving and suicidality among prison inmates: another look at state versus trait.

This research examines the relationships between means-ends problem solving and suicidality among adult male prison inmates in light of new evidence based on inpatient and college student populations suggesting that state, rather than trait, vulnerabilities may be responsible for problem-solving deficits and differences. Using the Means-Ends Problem-Solving Procedure (MEPS) with 93 state prison inmates, we found that among inmates with a history of parasuicide, current suicidality did not affect problem-solving performance. We further found that among nonsuicidal inmates, parasuicide history had no effect on problem solving or affect-suicidality measures. Although these results support new research suggesting that trait problem-solving deficits are not causally linked to suicidality, they raise questions about the potentially unique relationships among suicidality, problem solving, depression, and hopelessness in incarcerated populations.

The role of hopelessness and social desirability in predicting suicidal behavior: a study of prison inmates.

The purpose of this study is to further examine the relationships among hopelessness, social desirability, and suicidal behavior in the decade-long dispute about the role of social desirability and the ability of the Beck Hopelessness Scale to predict suicidal behavior. Using a stratified random sample of state prison inmates, we found that hopelessness and suicidal behavior remain significantly correlated even after social desirability is held constant, failing to replicate Linehan and Nielsen's (1981, 1983) findings. In addition, a multivariate regression analysis demonstrated that the utility of hopelessness in predicting suicidal behavior varies with the level of social desirability, consistent with Holden, Mendonca, and Serin's (1989) results describing an interaction between hopelessness and social desirability. Implications for the assessment of suicidality incorporating the role of social desirability are discussed.