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Biomedical subjects

S Pollack

Publications and source records attributed to S Pollack.

At least 73 records · Page 4Linked to original sources

Classic Kaposi's sarcoma: T-lymphocyte subsets, T4/T8 ratio, and NK cell activity.

Lymphocyte function as expressed by T-lymphocyte subsets and natural killer cell activity was evaluated in a group of Israeli patients with classic Kaposi's sarcoma. T-cell subsets were examined in 28 patients, 14 with lesions limited to the lower extremities and 14 with diffuse cutaneous or systemic involvement. CD4 and CD8 lymphocytes and CD4/CD8 ratio were in the normal range in all patients, and mean values of the entire group were similar to a control group. However, CD8 was in the upper limits of the normal range in some patients with diffuse cutaneous or systemic involvement. This factor led to a significantly decreased CD4/CD8 ratio in that group as compared with the group of patients with the disease limited to the lower extremities. Mean values of natural killer cell activity in three effector/target cell ratios were significantly decreased in 13 of the patients with Kaposi's sarcoma with lesions limited to the lower extremities and in all of the patients with normal T-cell subsets and CD4/CD8 ratios.

Adult

Influence of the mobile phase on salmon calcitonin analysis by reversed-phase liquid chromatography.

The retention properties of calcitonins on a reversed-phase column are examined using salmon calcitonin as the model compound. The effect of the concentration of organic modifier, buffer strength, pH of the mobile phase, and ion-pair reagent are studied. In the absence of an ionic modifier in the eluent the calcitonin peak shapes are not symmetrical. The addition of 0.1% trifluoroacetic acid (TFA), however, results in good peak characteristics without the need to add nonvolatile salts. The retention of the calcitonins was found to be very sensitive to the concentration of the organic modifier (acetonitrile) present in the mobile phase. A change of pH between 2 and 5 has only a slight effect of the k' of salmon calcitonin, but the k' increases significantly at higher pH values. The addition of a phosphate buffer to the mobile phase and an increase in the buffer concentration (0-0.2 M) causes a decrease in the retention of salmon calcitonin. Evidence shows that reproducible, quantitatively measurable data can be obtained using reversed-phase chromatography if the ion-pairing reagent and organic modifier concentrations are carefully controlled. The system also shows a good selectivity for the calcitonin series. Therefore, both highly selective methods (qualitative) as well as quantitative methods for analytical, pharmaceutical, and manufacturing use can be developed by adjusting the high-performance liquid chromatography (HPLC) conditions as discussed.

Amino Acid Sequence

The comorbidity of borderline personality disorder and other DSM-III-R axis II personality disorders.

OBJECTIVE: This study examines the comorbidity of DSM-III-R borderline personality disorder and the other axis II personality disorders. The extent and direction of overlap provides a measure of the clarity of its diagnostic boundaries and descriptive validity. METHOD: In 110 outpatients without concurrent major axis I conditions, axis II diagnoses were assessed in semistructured format and all DSM-III-R personality disorder criteria were rated. Multiple diagnoses were recorded. RESULTS: Twenty-two patients (20%) met criteria for borderline personality disorder; 18 (82%) had at least one additional personality disorder diagnosis. Using measures of frequencies and intercorrelation coefficients, the authors found that overlap was extensive and not confined to any one of the three designated axis II clusters. Factor analysis revealed 1) a group containing borderline personality disorder with paranoid, histrionic, narcissistic, antisocial, and passive-aggressive personality disorders and 2) another grouping of schizoid, schizotypal, avoidant, obsessive-compulsive, and self-defeating personality disorders. CONCLUSIONS: Borderline personality disorder appears to constitute a broad, heterogeneous category with unclear boundaries that embraces a general personality disorder concept. Both further refinement of the borderline personality disorder construct and investigation into alternative models to the DSM-III-R axis II classification system are suggested.

Adolescent

Psychological comorbidity and length of stay in the general hospital.

OBJECTIVE: As general hospitals search for ways to cut costs without sacrificing efficiency, particular attention has been focused on factors that may prolong hospital stay. The results of prior studies that have reported an association between psychological and psychiatric comorbidity and longer hospital stays have been subject to different interpretations because of methodological design flaws. The current paper reports on a study of psychological comorbidity and length of stay that has been designed to avoid the methodological problems of earlier investigations. METHOD: The study was performed at a 429-bed tertiary-care, university-affiliated, voluntary, teaching hospital. During hospital days 3 to 5, patients were tested as available with the Mini-Mental State examination, the Zung Depression Inventory, and the SCL-90 and were rated for physical impairment with the Karnofsky Performance Status Scale. Statistical analyses were performed for correlations between length of stay and test scores, rating scales, and demographic and discharge data from the chart. RESULTS: Of 424 patients approached, 321 (76%) agreed to participate and 278 (65.6%) completed the test battery. Depression, anxiety, and organicity, measured by psychological tests, were significantly correlated with longer hospital stay. These correlations remained significant after the authors controlled for degree of physical impairment, emergency versus elective admission, and medical versus surgical service, which were themselves correlated with longer hospital stay. DISCUSSION: This study confirms a significant correlation between psychological comorbidity and length of stay after correcting for the methodological pitfalls found in earlier studies. The clinical, research, economic, and policy implications of these findings are discussed.

Adolescent

The long term benefits of a comprehensive teenage pregnancy program.

A comprehensive program was founded in 1982 to provide adolescents with prenatal and family planning care. The program's impact through its first five years of operation on medical aspects of pregnancy course and fetal outcome will be the subject of a separate report. This study examines subsequent maternal and infant health of the patients attending the program compared to a control group. Four hundred ninety-eight adolescents and their newborns attending the program's mother-baby family planning clinic from 1982 to 1989 (subject group) were compared to ninety-one adolescents and their newborns receiving postpartum family planning and pediatrics clinics from 1980 through 1989 (control group). Seventy-five percent of the subject group regularly attended mother-baby clinic, compared to 18% of the control group attending family planning and pediatric clinics (P less than or equal to .0001). The subject group experienced less maternal and infant morbidity, greater school attendance, graduation, employment, and contraceptive use than the control group (P less than or equal to .0001). Many parameters improved with each program year indicating continued wide acceptance of our program by area adolescents.

Adolescent

The effects of clozapine on tardive dyskinesia.

This article reviews eight published studies that describe clozapine's effects on TD and examines the outcome of 30 patients with TD treated with clozapine for up to 36 months. These data indicate that TD response to clozapine is variable but that approximately 43% of cases, particularly those with dystonic features, improved after clozapine treatment. Methodological limitations of the studies described, however, preclude definitive conclusions, which must await appropriately controlled trials.

Adult

Two types of receptors for iron on mitochondria.

ATP, the major ligand for Fe in the reticulocyte's low-Mr chelatable pool, transfers Fe to a mitochondrial receptor from which the Fe is incorporated into haem. However, the utilization of Fe bound to this receptor for haem synthesis is slow in comparison with that bound to a second receptor that does not accept Fe from ATP, but does accept it from AMP. The major pathway by which Fe is delivered for haem synthesis may be through hydrolysis of cytosolic ATP-Fe to AMP-Fe.

Adenosine Monophosphate

CD-3-mediated activation of MAP-2 kinase can be modified by ligation of the CD4 receptor. Evidence for tyrosine phosphorylation during activation of this kinase.

The CD4R has been shown to exert variable effects on T cell activation responses. Depending on the manner of ligation, the CD4R has been demonstrated to have positive as well as negative effects on the generation of [Ca2+]i flux by the CD3R. Coaggregation of CD3 with CD4 enhanced Ca2+ flux while their independent ligation and aggregation diminished this response. To further elucidate these paradoxical CD4 effects, we studied induction of a microtubule-associated protein 2 kinase (MAP-2K) activity during ligation of the CD3R. Lymphoid MAP-2K activation by CD3 is an evanescent event that is dependent on phosphorylation of 43-kDa MAP-2K via a pathway that involves protein kinase C. Coaggregation of CD4 and CD3 with cross-linking antibodies and avidin enhanced the CD3-mediated MAP-2K response almost twofold. In contrast, independent ligation and cross-linking of CD4 reduced the CD3-induced MAP-2K response by approximately 50%. An important requirement for this inhibitory effect was that CD4 be ligated before stimulation with anti-CD3. The negative effect of anti-CD4 mAb was specific as other mAb failed to simulate this event. The PMA-induced MAP-2K response was not inhibited by anti-CD4. Intact 32P-labeled Jurkat and normal human T cells demonstrated the appearance of a single 43-kDa tyrosine phosphoprotein during stimulation with PMA and anti-CD3. When these crude cellular extracts were extensively fractionated across DEAE- and hydrophobic columns, MAP-2K was resolved into two peaks of activity, each containing a single tyrosine phosphoprotein around 43 kDa. In addition to tyrosine-specific labeling, mitogenic stimulation of normal human T cells also induced threonine-specific labeling of MAP-2K. These results imply that activation of lymphoid MAP-2K is a dual process requiring at least two independent kinases for optimal activity. Inasmuch as CD3 activates protein kinase C and CD4 is associated with a tyrosine kinase, pp56lck, we suggest that their coaggregation may create the conditions whereby MAP-2K may be activated by dual phosphorylation. Independent aggregation of these receptors may lead to physical separation and breakdown of this interactive mechanism.

Adult

Stimulation of MAP-2 kinase activity in T lymphocytes by anti-CD3 or anti-Ti monoclonal antibody is partially dependent on protein kinase C.

Signaling via the alpha-beta T cell Ag receptor (Ti)-CD3 complex is a complicated event that implicates several protein kinases, most notably protein kinase C (PKC). We have recently identified a serine kinase in T lymphocytes with the following characteristics: molecular mass 43 kDa, in vitro substrate affinity for microtubule associated protein 2 (MAP-2) with a preference for Mn2+ during the catalytic reaction, and elution from DEAE resin over a salt range 100 to 200 mM NaCl. This kinase is activated in a rapidly reversible fashion during ligation of CD3/Ti by a process which involves prior phosphorylation; in vitro exposure of activated 43-kDa MAP-2 kinase (MAP-K) to an immobilized phosphatase abrogated its kinase activity. We now show that a MAP-2K response could also be obtained during treatment with mAb to Ti and the specific PKC agonist, PMA. Although the kinetics of the former response was rapidly reversible, PMA elicited a more prolonged response. The dose responsiveness for PMA was similar to the requirements for PKC activation in intact lymphocytes. Moreover, as with PKC, we found that the CD3-induced MAP-2K response could be further enhanced by using a second layer cross-linking antibody. The specificity of CD3/Ti in the Jurkat cell response is demonstrated by the fact that OKT-11(CD2) and anti-CD4 mAb did not stimulate a MAP-2K response. It was also not possible to elicit a response in a Jurkat cell mutant that lacks surface expression of CD3 and Ti. The specificity of PKC in these events was further explored with the cell permeant diacylglycerol, 1-oleoyl-2-acetylglycerol, and the nonagonist phorbol ester, 4 alpha-phorbol 12,13-didecanoate: whereas the former was an effective inducer of the MAP-2K response, the latter failed to yield any stimulation. Prior exposure of Jurkat cells to 100 mM PMA for 24 h eliminated greater than 60% of the MAP-2K response during anti-CD3 treatment. This response could also be inhibited in dose-dependent fashion by prior treatment of Jurkat cells with the potent PKC inhibitor 1-(5-isoquinolinesulfonyl) 2-methylpiperazine dihydrochloride. Although a Ca2(+)-ionophore failed to synergize with PMA at inducing a MAP-2K response, depletion of extracellular Ca2+ by EGTA abrogated anti-CD3 responsiveness. The events culminating in MAP-2K activation were slightly inhibited in the presence of cholera toxin but not pertussis toxin.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal

Mitochondria have Fe(III) receptors.

Recent work has provided new evidence that ATP is the major constituent of the low-Mr iron pool in the reticulocyte. The interaction of the iron complex of ATP with mitochondria was investigated in the present experiments. When ATP-Fe3+ was incubated with mitochondria, Fe3+, free of ATP, bound with high affinity to Fe3+ receptors on the mitochondria. The binding was saturable and reversible. Iron which was complexed to PPi, nitrilotriacetate, citrate, ADP and GTP also showed saturable binding to mitochondria; Fe3+ complexed to AMP bound non-specifically, as did Fe2+/ascorbate complexed to AMP bound non-specifically, as did Fe2+/ascorbate and Fe2+/dithionite.

Adenosine Triphosphate

Iron bound to low MW ligands: interactions with mitochondria and cytosolic proteins.

The iron in the low MW pool of the cell is the precursor of iron in haem and is bound primarily to ATP. This precursor-product relationship suggested that reticulocytes might accumulate ATP-iron if their haem synthesis were blocked. However reticulocytes, treated with succinylacetone or rotenone and taking up iron from transferrin, accumulated iron in nonhaem cytosolic proteins and in mitochondria and not in the low MW pool. This was demonstrated by NMR and also by disrupting the cell with shear stress, separating the cytosol and pellet and fractionating the cytosol with ammonium sulfate. This constancy of the low MW iron pool in the face of blocked haem synthesis could not be explained by saturation of cytosolic ATP or by sluggish exchange of the low MW pool with other compartments. Rather, nonhaem cytosolic proteins and mitochondria appeared to have a higher affinity for iron and to exchange it rapidly with that in the low MW pool.

Animals

Two pathways for iron uptake by guinea pig reticulocytes.

We have demonstrated that the intracellular processing of transferrin to effect iron removal involves two pathways, one sensitive to rotenone and the other not. We have also found that the effect of the rotenone is dependent on the transferrin concentration: iron uptake was suppressed with concentrations of transferrin in the micromolar range, and was not suppressed at physiologic concentrations of transferrin. Rotenone does not disturb transferrin's interaction with its extracellular receptor, indicating that its action must be intracellular. The following model is suggested: that separate pathways are entered by transferrin in the cell. The first pathway is preferentially utilized when transferrin is in short supply. It begins with an intracellular site which has a high affinity (and low capacity) for either iron or transferrin. The second pathway begins with an intracellular site which has a high capacity (but low affinity) for either iron or transferrin and is utilized when transferrin is in physiologic concentration (and the low-capacity, high-affinity site is saturated); the pathway it initiates is dominant when transferrin is abundant. We speculate that the high-affinity low-capacity pathway may serve to direct intracellular iron to sites which would be critically injured by iron excess.

Animals

Iron binding to apotransferrin.

The classic analysis of metal transfer between ligands suggests that the metal-binding ligand (M-L1) and the uncomplexed ligand (L2) form a mixed complex (L2-M-L1), and that transfer is effected with the dissociation of this complex to L2-M and L1. Spectroscopic data suggested that such mixed complexes formed when pyrophosphate-Fe and acetohydroxamate-Fe were added to apotransferrin: the initial species had a different absorbance maximum than the final transferrin-iron complex. We now show that similar spectroscopic changes are seen when free ferrous iron or iron liganded to ATP, citrate or nitrilotriacetate are added to apotransferrin. The evolving spectrum on the addition of iron to apotransferrin may thus reflect iron binding per se rather than the formation of a mixed ligand complex.

Adenosine Triphosphate

Decreased natural killer cell function in patients with classical Kaposi's sarcoma.

Natural killer (NK) cell activity of peripheral blood lymphocytes was evaluated in a group of 13 patients with classical Kaposi's sarcoma (KS). All patients had a normal T4/T8 ratio, and the disease was confined to the skin of the lower extremities. A group of 5 healthy subjects served as controls. NK cell function was significantly decreased in patients as compared to controls. Our result is similar to that found in another group of patients with AIDS-related KS with lymphadenopathy and an abnormal T4/T8 ratio. This suggests that decreased NK cell function is not a result of a progressive process and might be directly involved in the development of KS.

Aged

NMR studies of intracellular free calcium, free magnesium and sodium in the guinea pig reticulocyte and mature red cell.

During the maturation process reticulocytes lose their intracellular organelles and undergo changes in membrane lipid composition and ion transport properties. While several reports indicate differences in the levels of magnesium, sodium and calcium in reticulocytes and erythrocytes, controversy remains concerning the actual magnitude and direction of ionic alterations during reticulocyte maturation. One problem with all of these studies is that the techniques used are invasive and are limited to measuring only the total cell ion content. We have used 31P, 23Na and 19F nuclear magnetic resonance (NMR) spectroscopy to compare the intracellular free ion and phosphometabolite levels in guinea pig reticulocytes and mature red blood cells. In contrast to a sharply decreased concentration of ATP in erythrocytes in comparison to reticulocytes, the intracellular free magnesium, measured using 31P-NMR, was increased by about 65% upon maturation (150 mumol/l cell water in reticulocytes in comparison to 250 mumol/l cell water in erythrocytes). Sizeable but opposite changes in intracellular sodium (5.5 mumol/ml cells in reticulocytes vs. 8.5 mumol/ml cells in erythrocytes) and intracellular free calcium (99 nM vs. 31 nM in reticulocytes and mature red cells, respectively) were also observed, suggesting that alterations in the kinetics of membrane ion transport systems, accompanying changes in phospholipid and cholesterol content, occur during the process of red cell maturation. However, in contrast to dog red blood cells, there was no evidence for the presence of a Na+/Ca2+ exchanger in guinea pig reticulocytes or erythrocytes.

Animals