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Biomedical subjects

G Serban

Publications and source records attributed to G Serban.

At least 19 recordsLinked to original sources
PubMed1999

The effects of low density lipoproteins modified by incubation with chondroitin 6-sulfate on human aortic smooth muscle cells.

One of the first changes that take place within the artery intima at the inception of atherosclerosis is the accumulation of LDL-derived modified lipoproteins which appear as subendothelial lipid droplets and vesicles. With time, the LDL retention and interaction with intimal chondroitin sulfate-proteoglycans may induce further structural and functional modification of the lipoproteins. The aim of this study was to produce 'in vitro' modified lipoproteins by LDL incubation with chondroitin 6-sulfate (CS, at 37 degrees C, for 48 h, in the absence of antioxidants) and to test their effects on cultured human aortic smooth muscle cells (SMCs). CS induced LDL modification (CS-mLDL) consisted in formation of a mixture of fused particles (up to 150 nm diameter) and monomers with a small content of lipid peroxides and a partially degraded apo B-100, corresponding to a mild oxidation. Upon incubation with SMCs, CS-mLDL produced a concentration-dependent stimulation of 3H-thymidine incorporation, that, at low concentration (25 microg/ml), was 2-3-fold higher than that obtained when native LDL was used; this increase correlates well with the level of CS-mLDL uptake at the same concentration. Besides the mitogenic effect, CS-mLDL induced a significant stimulation of SMCs migration, comparable with that reported for oxidized LDL. Upon incubation with CS-mLDL, SMCs accumulated lipid droplets of various number and dimension, as revealed by Nile red staining and electron microscopy. Competition studies performed in the presence of 20-fold excess of native LDL and acetyl LDL showed that 125I-CS-mLDL were taken up both by LDL receptor and scavenger receptor. At high concentration (200 microg/ml), CS-mLDL had a cytotoxic effect that was not significantly different from that of native LDL. Together these results provide evidence of (i) the direct alteration produced by CS on LDL and (ii) the effect of CS-mLDL on SMCs migration, proliferation and transformation in lipid-laden cells, events that are crucial in the development of fibro-muscular atherosclerotic lesions.

Aorta↗
PubMed1999

High glucose induces enhanced monocyte adhesion to valvular endothelial cells via a mechanism involving ICAM-1, VCAM-1 and CD18.

Upon induction of experimental hyperglycemia (i.e. diabetes) pathological modifications are early detected (approximately 7 days) at the level of the cardiac valves leading rapidly to the development of valvular atheroma. Monocyte adhesion to the vascular endothelium is one of the initial event at the onset of atherosclerosis. We questioned whether high glucose enhances monocyte adhesion to the valvular endothelial cells (VEC) so as to explain, in part, the accelerated atheroma formation that occur in diabetic conditions. To this purpose we compared the adhesion of monocytes to VEC cultured in 5.5 mM (normal) glucose (NG) or in 33 mM (high) glucose (HG) or in high mannitol (HM) (27.5 mM mannitol plus 5.5 mM glucose), a concentration known to simulate the hyperosmolar effect of high glucose. After incubation for 30 min at 37 degrees C, the adhesion of monocyte cell line (U937 cells) to VEC was quantitated by a fluorimetric assay or by direct counting. Statistical data showed a significant increased adhesion of monocytes to VEC grown in HG (up to 4 fold) or in HM (up to 2.7) when compared to normal conditions. Using a battery of specific monoclonal antibodies molecules it was found that the increased adhesion of monocytes to VEC grown in high glucose was specifically inhibited (p < 0.05) by anti-ICAM-1, anti-VCAM-1 and anti-CD18 monoclonal antibodies. Together, the results indicate that high glucose induces enhanced monocyte adhesion to VEC via a mechanism involving in part an osmotic effect and mainly the cell adhesion molecules: ICAM-1, VCAM-1 and CD18.

Animals↗
PubMed1997

Transcytosis of albumin in endothelial cells is brefeldin A--independent.

To determine whether in endothelial cells (EC) the pathways of endocytosis and transcytosis of macromolecules interconnect, the effect of Brefeldin A (BFA) on these processes was tested. To this purpose EC were grown to confluence on plastic culture dishes or on cell culture chamber inserts placed into corresponding wells, so as to obtain a dual chamber system. The cells maintained the typical characteristics of EC and had an electrical resistance in the range of 30-60 Ohm.cm2. Transendothelial transport of albumin conjugated to the fluorochrom Texas Red (Alb-TR) and of horseradish peroxidase (HRP) added to the upper compartment, in the absence or presence of BFA (0-25 micrograms/ml), was evaluated in aliquots collected from the lower compartment. At different time intervals, quantitative data were obtained by fluorimetry and spectrophotometry. In other experiments transcytosis of Alb-TR was examined in the presence of 100 microM forskolin (an inhibitor of BFA effect). The endocytosis of Alb-TR and HRP was evaluated by incubating EC with the probes, and the internalized tracers determined in the cell lysate using the methods described above. The results showed that BFA has no significant effect on transcytosis of albumin and HRP. In contradistinction, BFA (5 micrograms/ml) reduced markedly endocytosis of HRP (by 47%). Forskolin has no effect on transcytosis. The data indicate that the BFA-induced perturbance in the endocytic route does not affect the transcytotic pathway of albumin, and suggest that in EC, transcytosis of macromolecules may represent a shortcut for rapid and direct transport of some plasma molecules across the cell.

Animals↗
PubMed1997

Expression of transferrin receptors in endothelial cells transfected by electroporation.

Transferrin is the primary iron-binding protein in the plasma. Transferrin receptors (TfR) were detected in brain and liver endothelial cells (EC); however, little information exists about their intracellular routes. To detect the EC structures involved in TfR biosynthetic and endocytotic pathways, cultured aortic EC were transfected with the plasmid pSR alpha containing a construct encoding the human TfR, to which horseradish peroxidase (HRP) was anchored as reporter molecule. Since EC are difficult to be transfected, we tried different techniques, and two forms of the plasmid (circular and linearized), of which the electroporation method and the linearized plasmid were the most efficient in producing stable cell lines. Transfected cells were selected with geneticin, and the expression of TfR-HRP tested by cytochemistry. The stable transformants preserved the general characteristics of EC. At the ultrastructural level, TfR-HRP was associated with the nuclear envelope, rough endoplasmic reticulum, Golgi complex and adjacent secretory vesicles, cytoplasmic vesicles of various sizes (50-130 nm diameter), endosomes, plasma membrane, plasmalemmal pits, and a fraction of plasmalemmal vesicles. The intensity of the reaction product varied, suggesting a different concentration of TfR, in specific organelles. For example, (i) a gradient of HRP-reaction product was found within the Golgi cisternae, (ii) the plasmalemmal pits were more intensely stained than the adjacent plasma membrane, and (iii) the vesicle membrane was decorated stronger than the endosomal membrane (to which it fuses). A striking feature was the coexistence within the same EC of two vesicle populations (or subtypes): some containing TfR-HRP, whereas others lack the receptor. Quantitative data indicated a stronger expression of TfR in confluent cells (approximately 8-fold higher) than in EC at 2 days after plating; a significant decrease (approximately 9-fold) of TfR was found in postconfluent transfectants. Together, the data demonstrate that (i) after electroporation of EC, the stable lines maintain the characteristics of native cells; (ii) the newly synthesized TfR is located in variable concentration within the organelles involved in endocytosis and exocytosis, and (iii) the expression of TfR-HRP is particularly high in confluent cells.

Animals↗
PubMed1996

Identification of albumin-binding proteins of thymocyte plasmalemma.

In the present work we examined whether the interaction between albumin molecules and thymocytes involves albumin-binding proteins (ABP). Two plasmalemma-rich fractions obtained by differential centrifugation from rat thymus lymphocytes were characterized biochemically and morphologically. These fractions were examined by ligand-blotting and ligand affinity chromatography techniques. Plasmalemma proteins separated by SDS-PAGE were electrotransferred onto nitrocellulose membranes and incubated with 125I-albumin, in the presence or absence of excess native albumin. The autoradiogram revealed specific binding to two sets of polypeptides of 16-18 and 29-31 kDa, which could be blocked by native albumin. To elucidate whether albumin-binding proteins are exposed on the cell surface, intact lymphocytes were surface radioiodinated and membrane fractions prepared from them were subjected to affinity chromatography on albumin-agarose beads. The protein thus purified had, like ABP, M(r) of 16 and 31. These data indicate that ABP (i) are components of thymocyte plasma membrane, (ii) have apparent molecular mass of 16-18 and 29-31 kDa, and (iii) are exposed on the outer membrane surface.

Albumins↗
PubMed1992

Multiple personality: an issue for forensic psychiatry.

The formulation of Multiple Personality (MP) as a distinctive entity by DSM-III while helpful clinically requires, at best, very rigid evaluatory criteria based on independent verification when used as a defense in a Court of Law. The use of the set of eight criteria developed by specialists are helpful guidelines. A case of MP disorder discovered under hypnosis by a psychiatrist and later on vehemently denied by the patient became the object of legal action as part of a malpractice suit. While some well-known experts consulted during treatment believed that she was a MP, the expert witnesses at the trial felt that the patient was not. As a mixed (borderline-histrionic) personality, the patient possibly might have dissociated under stressful life circumstances. The case raises serious issues about the role of auto-suggestion in mimicking MP. It questions the validity of the use of the diagnosis in Court. Legally only carefully evaluated independent data about incongruent past patterns of behavior suggesting alternate personality, can be considered reliable reference for the diagnosis.

Adult↗
PubMed1992

Response of negative symptoms of schizophrenia to neuroleptic treatment.

BACKGROUND: In view of the inconclusive reports in the literature about the response to neuroleptics of chronic schizophrenics with negative symptoms, the authors further evaluated this issue. METHOD: A sample of 30 ambulatory chronic schizophrenics meeting DSM-III-R criteria who had to a marked degree at least two negative symptoms of the five on the Scale for the Assessment of Negative Symptoms (SANS) received various therapeutic dosages of thiothixene for 3 months. The average dose was 26.75 mg/day. Subjects were periodically evaluated with the Brief Psychiatric Rating Scale, Negative Symptoms Rating Scale (a modified version of the SANS), and the Randt Memory Test. The time effect on treatment was calculated by repeated measures of analysis of variance. The relationship between the positive and negative symptoms was tested by an analysis of covariance. RESULTS: Both negative and positive symptoms improved with treatment. The negative symptoms tended to respond to treatment predominantly independently of the positive ones. At the end of the study, 63% (N = 19) of patients had improved moderately, 16% (N = 5) had improved slightly, and 20% (N = 6) had not improved. CONCLUSION: The data require further support from a long-term follow-up study that may show the extent to which these gains are maintained over time.

Adult↗
PubMed1990

Computed tomography scans and negative symptoms in schizophrenia: chronic schizophrenics with negative symptoms and nonenlarged lateral ventricles.

Computed tomography scans of 31 chronic schizophrenics with negative symptoms and 31 age-matched normal volunteers were assessed for ventricular size, cortical atrophies, third ventricle diameter, and cerebellar atrophies. No significant differences were found in the size of the lateral ventricles or third ventricles between the chronic schizophrenics and the controls. The frontal horns in patients did show a tendency toward increased size compared with controls. Sulci width showed significant differences between patients and controls. The clinical variables, except for the memory test, did not correlate with any brain morphology. A meta-analysis was performed on 17 studies that used the planimetric method in order to evaluate the relationships between the size of the lateral ventricles in patients and their respective controls. We found significant differences between the group of studies using normal controls and the group using medical controls.

Adult↗
PubMed1987

Borderline and schizotypal personality disorders: mutually exclusive or overlapping?

This article is concerned with one aspect of the validity of DSM-III Axis II diagnoses, namely, the discriminability of borderline and schizotypal disorders. Forty-nine patients diagnosed by DSM-III criteria as borderline, schizotypal, or "mixed" personality disorders completed the Borderline Syndrome Index (BSI), an independent self-report 52-item instrument that has been shown to be reliable and to have discriminative validity. A one-way analysis of variance and a discriminant function analysis were conducted. Our major finding was that there were no significant differences among the groups on the BSI self-report test, although there were differences on clinical grounds. We discuss this in terms of "fuzzy set" theory and prototypic systems of classification.

Adult↗
PubMed1984

Response of borderline and schizotypal patients to small doses of thiothixene and haloperidol.

The improvement in the clinical methods of identifying borderline subjects makes it necessary to reevaluate the efficacy of the treatment offered them. A random sample of 52 borderline and schizotypal patients was treated with two major neuroleptics, thiothixene and haloperidol, in a double-blind study. Eighty-four percent were markedly to moderately improved at 3-month follow-up; the patients responded better to thiothixene than to haloperidol. The main areas of positive response were those of cognitive disturbance, derealization, ideas of reference, anxiety, and depression. The patients also showed improvement in self-image and social functioning. There was no significant relationship between diagnosis and outcome of treatment.

Adult↗
PubMed1981

Sexual activity in therapy: legal and ethical issues.

The new modalities of therapy based on sensitivity training and behavioral modifications techniques, including sexual therapy, have changed the relationship between therapist and patient, making the therapist vulnerable to malpractice suits. The whole legality of the court cases involving sexual intimacy between patient and doctor in the mental health field relies essentially on the interpretation of transference, a questionable psychological concept, but its court value is even more disputable since the damages are ill-defined from the psychological point of view. The ethical aspect of this issue, however, rests primarily on the Hippocratic oath which rightly attempts to separate therapeutic from nontherapeutic practicing of care. Yet, if the sexual interaction as a part of behavior modification is included under care, this changes even the existing concept of the ethical code. We need a better regulation of the doctor-patient relationship in order to avoid the intrusion of a questionable legality which for the most part rests on untested psychological dynamics.

Ethics, Professional↗
PubMed1979

Mental status, functioning, and stress in chronic schizophrenic patients in communicity care.

The author studied the interactions between functioning, stress, and psychological deficit, variables considered essential to the schizophrenic patient's adjustment in the community. The results indicate that comprehensive measurement of functioning and stress correlates significantly with mental status. A breakdown by the components of functioning and stress revealed further areas of interaction between these variables. An important finding was that anxiety contributed maximally to the prediction of stress and depression to that of functioning. These data seem relevant to the schizophrenic patient's degree of social adjustment in the community.

Adaptation, Psychological↗
PubMed1979

Relationship between cognitive defect, affect response and community adjustment in chronic schizophrenics.

The relationship between mental status and community adjustment has been examined in 100 outpatient chronic schizophrenics. Sixty-six per cent presented at least one of the signs of Schneiderian First Rank Symptoms, which, however, failed to discriminate the diagnostic subgroups. Total adjustment correlated with total mental status and appeared to differentiate the diagnostic subclassifications of schizophrenia. From the major components of mental status, anxiety and depression appear to be significantly correlated with the functioning and stress of the individual in community adjustment while primary symptoms are only peripherally correlated with adjustment.

Adult↗
PubMed1978

New approach to the rehabilitation of the hard core drug addict (heroin methadone addicts) a pilot community study.

The limitation of the methadone maintenance program has pressed for a re-evaluation of our understanding of the underlying causes of addiction. Apparently, one of theunderlying causes or end result produced by the drug itself is that of depression. It explains why the addicts try to maintain to the maximum, the euphoric state and are unwilling to rehabilitate. A pilot study was conducted for the treatment of ex-methadone addicts with large dosages of antidepressants and anxiolytics. Out of 117 ex-methadone and soft drug addicts treated with antidepressants and anxiolytics, 46% ex-methadone and 46.3% soft drug abusers failed to become abstinent. The failures were basically related to the management of treatment. The study suggests a possibility for detoxification from methadone and control of relapse by antidepressants and anxiolytics.

Anti-Anxiety Agents↗
PubMed1975

Differentiating criteria for acute-chronic distinction in schizophrenia.

Type of onset, presence of precipitating events, mental status, and premorbid instrumental functioning, commonly associated with prognosis in schizophrenia, were studied in relation to the acute-chronic distinction and short-term outcome in 641 schizophrenic patients. Contrary to the general position held by some researchers, none of the clinical predictors (type of onset, precipitating crises, and mental status) appeared to distinguish the two types of schizophrenics, or to contribute substantially to the prediction of readmission. Preadmission social functioning of the two patient groups was more similar than generally indicated by previous reserach. As regards prediction of short-term rehospitalization, the study identified poor relationships with parents, friends, and opposite-sexed peers as important factors for acute patients and antisocial behavior and inability to relate to the opposite sex and others in the community as important variables for chronic patients.

Acute Disease↗
PubMed1975

Relationship of mental status, functioning and stress to readmission of schizophrenics.

A study was conducted to determine the interrelations among the variables of patient functioning, life stress, mental status and readmission to the hospital after release. The population consisted of 516 chronic and 125 acute schizophrenic men and women. Stress and functioning were measured by the Social Stress and Functionability Inventory for Psychotic Disorders. Mental status was assessed through the use of a standard Problem Appraisal inventory. Results demonstrated that mental status variables correlated at a low level with readmission, accounting for a minimal amount of variance, and that the factor of patient functioning had more predictive value, but its effectiveness was hampered by the long-standing cycle of admission-release-readmission in regard to chronic patients. Apparently there is no justification for considering mental status as a factor in prognosis, as some researchers have done in the past, based on the same low correlations.

Adaptation, Psychological↗
PubMed1975

The phenomenology of depression.

The article attempts to identify the basic mechanism of depression as implied by various clinical formulation of depression. In this context, depression appears to result from a faulty system of thinking, developed during the individual's formative years. The depressed person perceives reality based on either absoluted social moral values or distorted evaluations of his limitations and expectations.

Adult↗