Brief report: recurrent severe infections caused by a novel leukocyte adhesion deficiency.
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Biomedical subjects
Publications and source records attributed to S Pollack.
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Cerebrospinal fluid studies have reported that low concentrations of the dopamine metabolite homovanillic acid are associated with suicidal behavior in depression. Although only a small proportion of homovanillic acid in the urine derives from the brain, we decided to examine 24-hour urinary outputs of homovanillic acid in relation to suicidal behavior in depression. Patients with depression who had attempted suicide had significantly smaller urinary outputs of homovanillic acid, dihydroxyphenylacetic acid, and total body output of dopamine (sum dopamine) than did patients with depression who had not attempted suicide. Patients with depression who reattempted suicide during 5-year follow-up had significantly smaller urinary outputs of homovanillic acid and sum dopamine than did patients who did not reattempt suicide, patients who never attempted suicide, and normal control subjects, and had significantly smaller outputs of dihydroxyphenylacetic acid than patients who never attempted suicide or control subjects. These data suggest that urinary outputs of homovanillic acid may be peripheral correlates of suicidality in depression. These data add to data on the low levels of homovanillic acid in cerebrospinal fluid in suggesting that diminished dopaminergic neurotransmission may play a part in suicidal behavior in depression.
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Spouse and adult child caregivers of older adults with major depressive disorder (N = 150) were asked what was most difficult and most rewarding about providing assistance to their relatives. Content analysis of their responses revealed seven areas of difficulty and three areas of reward. Difficulties and rewards were selectively associated with the caregiver's identity, patient clinical characteristics, and caregiver emotional adjustment. Caregiver perceived family difficulties and emotional difficulties were associated with the course of patient psychiatric illness over 1 year.
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Familial Mediterranean fever (FMF) is an inherited disorder of unknown etiology characterized by recurrent episodes of serous membrane inflammation. Interleukin 1 (IL-1) is a mediator of inflammatory processes. We hypothesized that IL-1 may play a role in acute attacks of FMF. Thus we tested IL-1 production by monocytes derived from patients with FMF. Nine patients were tested during acute attacks and 9 were asymptomatic when tested. Monocytes derived from peripheral blood of patients and controls were stimulated with lipopolysaccharide (LPS) and IL-1 activity in the supernatant was tested using a T helper cell line (D10-4G.1). IL-1 secretion during acute attacks was decreased whereas IL-1 production in asymptomatic patients was comparable to healthy controls. Followup of symptomatic patients during the recovery period revealed normalization of IL-1 secretion. Addition of indomethacin (prostaglandin E2 inhibitor) to LPS stimulated monocytes did not change IL-1 activity in patients or healthy controls. We conclude that in vitro IL-1 activity in patients with FMF is associated with the intensity of the inflammatory process.
Ligation of CD3/TCR on T-cells induces transient activation of lymphoid MAP-2 kinase (MAP-2K), a 43 kDa serine kinase which itself is a substrate of an unidentified tyrosine kinase (pp43). The reversibility of the MAP-2K response agrees with removal of tyrosine phosphates from pp43. Since both activity as well as tyrosine phosphorylation of MAP-2K could be prolonged by Na3VO4, a phosphotyrosine phosphatase inhibitor, we studied the effect of the common CD45 isoform, which is a member of the CD45 phosphatase family, on MAP-2K activity in vivo and in vitro. We demonstrate the ability of purified CD45 phosphatase to remove tyrosine phosphates from partially purified lymphoid MAP-2K. Utilizing the approach of heterologous receptor aggregation, we also showed that CD45 could inhibit the induction of MAP-2K activity in intact Jurkat cells during CD3 or CD3 + CD4 stimulation. We therefore suggest that this phosphatase may control the activity of lymphoid MAP-2K in vivo.
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Eight children aged between 1.3 and 13 years suffering from epilepsy refractory to conventional anticonvulsive therapy were treated with high dose intravenous gamma globulin (200 mg/kg, 3 times per week, repeated after 3 weeks). Immunological studies after therapy showed normal results. In four children, clinical and EEG findings markedly improved. In one other case a partial response was noted. No improvement was observed in the remaining three cases. We confirm that although the mechanism is still obscure, high doses of i.v. gammaglobulin may have a beneficial effect in a significant number of children with intractable epilepsy.
Salivary electrolyte secretion is under the control of the autonomic nervous system. In this paper we report that HSY, an epithelial cell line derived from the acinar-intercalated duct region of the human parotid gland, responds to muscarinic-cholinergic (generation of Ca2+ signal) and beta-adrenergic (generation of cAMP signal), but not to alpha-adrenergic (lack of Ca2+ signal), receptor stimulation. The muscarinic response was studied in detail. Carbachol (10(-4) M, muscarinic agonist) or A23187 (5 microM, calcium ionophore) stimulation of HSY cells increases both 86Rb (K+) influx and efflux, resulting in no change in net equilibrium 86Rb content. Atropine (10(-5) M, muscarinic antagonist) blocks both the carbachol-generated Ca2+ signal and carbachol-stimulated 86Rb fluxes, but has no effect on either the A23187-generated Ca2+ signal or A23187-stimulated 86Rb fluxes. Carbachol- and A23187-stimulated 86Rb fluxes are substantially inhibited by two K+ channel blockers, quinine (0.3 mM) and scorpion venom containing charybdotoxin (33 micrograms/ml). The inhibition of these stimulated fluxes by another K+ channel blocker, tetraethylammonium chloride (5 mM), is less pronounced. Protein kinase C (PKC) seems to be involved in the regulation of the 86Rb fluxes as 10(-7) M PMA (phorbol ester, phorbol-12-myristate-13-acetate) substantially inhibits the muscarinic-stimulated 86Rb efflux and influx. Because this concentration of PMA totally inhibits the carbachol-generated Ca2+ signal and only 80% of the muscarinic-stimulated 86Rb influx, it seems that a portion of the carbachol-stimulated 86Rb flux (i.e. that portion not inhibited by PMA) might occur independently of the Ca2+ signal. PMA fails to inhibit the A23187-stimulated 86Rb fluxes, however, suggesting that PKC regulates Ca(2+)-sensitive K+ channel activity by regulating the Ca2+ signal, and not steps distal to this event. 4-alpha-Phorbol-12,13-didecanoate, a phorbol ester which fails to activate PKC, fails to inhibit either the carbachol-stimulated increase in intracellular free Ca2+, or carbachol-stimulated 86Rb fluxes.
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.
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.
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.