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Biomedical subjects

R Sturm

Publications and source records attributed to R Sturm.

At least 91 records · Page 5Linked to original sources
PubMed1995

Mental health care utilization in prepaid and fee-for-service plans among depressed patients in the Medical Outcomes Study.

OBJECTIVE: We compare mental health utilization in prepaid and fee-for-service plans and analyze selection biases. DATA SOURCE: Primary data were collected every six months over a two-year interval for a panel of depressed patients participating in the Medical Outcomes Study, an observational study of adults in competing systems of care in three urban areas (Boston, Chicago, and Los Angeles). STUDY DESIGN: Patients visiting a participating clinician at baseline were screened for depression, followed by a telephone interview, which included the depression section of the NIMH Diagnostic Interview Schedule. Patients with current or past lifetime depressive disorder and those with depressed mood and three other lifetime symptoms were eligible for this analysis. We analyze mental health utilization based on periodic patient self-report. ANALYTIC METHODS: We use two-part models because of the presence of both nonuse and skewness of use. Standard errors are corrected nonparametrically for correlations across observations due to clustered sampling within participating physicians and repeated observations on the same individual. PRINCIPAL FINDINGS: The average number of mental health visits was 35-40 percent lower in the prepaid system, adjusted and unadjusted for observed differences in patient characteristics, including health status. Utilization differences were concentrated among patients of psychiatrists, with only minor differences among patients of general medical providers. Analyzing the effect of switches that patients make between payment systems over time, we found some evidence of adverse selection into fee-for-service plans based on baseline utilization, but not based on utilization at the end of the study. In particular, after adjusting for observed patient characteristics and health status, patients switching out of prepaid plans had higher baseline use than predicted, whereas patients switching out of fee-for-service had lower use than predicted. Switching itself appears to be related to an immediate decline in utilization and was not followed by an increase or "catch-up" effect. CONCLUSIONS: The absence of the commonly found "catch-up" effect following switching and the significant decrease in utilization during the switching period suggests an interruption in care that does not occur for patients staying within a payment system. This finding emphasizes the need for integrating new patients quickly into a system, an issue that should not be neglected in the current policy discussion.

Boston↗
PubMed1994

Switches between prepaid and fee-for-service health systems among depressed outpatients: results from the Medical Outcomes Study.

We analyzed switches between prepaid and fee-for-service health care plans among depressed outpatients in the longitudinal part of the Medical Outcomes Study. Patients of mental health specialists in fee-for-service plans had the lowest adjusted rate of plan switching (8.1%), compared to fee-for-service general medical patients (13.5%) and prepaid patients of both types of providers (10.1% to 11.7%). Although there were no substantial differences in initial sickness by payment system among enrolled patients, differing switching rates by provider specialty and payment system indicated biased selection over time. In addition, we found that married, nonwhite, and wealthier individuals were significantly more likely to leave fee-for-service than prepaid care plans. We analyzed whether system switching had an effect on patient satisfaction and outcomes. None of the results were highly significant, but the power of the data to analyze this issue was limited. Nevertheless, it appears that patients switching from prepaid to fee-for-service may be at risk for poorer functioning outcomes, although there was no similar effect on mental health status.

Adult↗
PubMed1993

Outcomes for adult outpatients with depression under prepaid or fee-for-service financing.

OBJECTIVE: To compare change over time in symptoms of depression and limitations in role and physical functioning of patients receiving prepaid or fee-for-service care within and across clinician specialties. METHOD: Observational study of change in outcomes over 2 years for 617 depressed patients of psychiatrists, psychologists, other therapists, and general medical clinicians in three urban sites in the United States. RESULTS: Psychiatrists treated psychologically sicker patients than other clinicians in all payment types. Among psychiatrists' patients, those initially receiving prepaid care acquired new limitations in role/physical functioning over time, while those receiving fee-for-service care did not. This finding was most striking in independent practice associations but varied by site and organization. Patients of psychiatrists were more likely to use antidepressant medication than were patients of other clinicians, but among psychiatrists' patients, there was a sharp decline over time in the use of such medication in prepaid compared with fee-for-service care. Outcomes did not differ by payment type for depressed patients of other specialty groups, or overall. CONCLUSION: Depressed patients of psychiatrists merit policy interest owing to their high levels of psychological sickness. For these patients, functioning outcomes were poorer in some prepaid organizations. The nonexperimental evidence favors (but cannot prove) an explanation based on care received, such as a reduction in medications, rather than on preexisting sickness differences.

Adult↗
PubMed1993

Pharmacological characterization of WAY-121,520: a potent anti-inflammatory indomethacin-based inhibitor of 5-lipoxygenase (5-LO)/phospholipase A2 (PLA2).

WAY-121,520 inhibited human synovial fluid PLA2 (HSF-PLA2) (IC50 = 4 microM) using arachidonic acid-labeled E. coli as substrate. Further biochemical characterization of WAY-121,520 demonstrated potent inhibition of 5-lipoxygenase (5-LO) activity in the murine macrophage (LTC4, IC50 = 4 nM) and rat PMN (LTB4, IC50 = 10 nM) and an ability to antagonize LTD4 binding to isolated guinea-pig trachea (pKB = 6.0). In vivo anti-inflammatory activity was noted in murine TPA-induced (ED50 = 91 micrograms/ear) and arachidonic acid-induced (66% inhibition at 400 micrograms/ear) ear edema and in leukotriene-dependent antigen-induced bronchoconstriction in the guinea pig (73% inhibition at 50 mg/kg, p.o.). WAY-121,520 represents a novel series of indomethacin-based inhibitors of PLA2 with anti-inflammatory activity resulting from a combination of biochemical activities (inhibition of 5-LO and PLA2 and LTD4 antagonism). This agent may provide added therapeutic efficacy over more selective inhibitors.

Animals↗
PubMed1993

Structure-activity relationships leading to WAY-121,520, a tris aryl-type, indomethacin-based, phospholipase A2 (PLA2)/leukotriene biosynthesis inhibitor.

We were intrigued by reports of the inhibition of phospholipase A2 (PLA2) by indomethacin. In order to increase the potency of the indomethacin system as an inhibitor of PLA2, it was decided to make more lipophilic analogs. Indeed, covalent attachment of a quinoline ring to the methoxy substituent of indomethacin affords WAY-122,220 which is almost an order of magnitude more potent than indomethacin in inhibiting human synovial fluid PLA2 (IC50 = 15 and 145 microM, respectively). The N-p-chloro-benzyl analog of this compound, WAY-121,520, was an even more potent inhibitor of PLA2 (IC50 = 4 microM). Structural analyses and molecular modeling suggest that these compounds may inhibit PLA2 by mimicking arachidonic acid. WAY-121,520 is also a potent leukotriene biosynthesis inhibitor both in the rat PMN and mouse macrophage assays (IC50 = 10 and 4 nM, respectively), possibly acting via a 5-LO (5-lipoxygenase) translocation inhibition mechanism. The multiple actions of WAY-121,520 may contribute to its favorable anti-inflammatory profile.

Animals↗
PubMed1992

Effects of progesterone on gonadotropin-releasing hormone receptor concentration in cultured estrogen-primed female rat pituitary cells.

Acute (0.5-4 h) treatment of estradiol (E)-primed female rat pituitary cells with progesterone (P) augments gonadotropin-releasing hormone (GnRH)-induced LH release, whereas chronic (48 h) P-treatment reduces pituitary responsiveness to the hypothalamic decapeptide. Dispersed E-primed (48 h, 1 nM) rat pituitary cells were cultured for 4 or 48 h in the presence of 100 nM P to assess the effects of the progestagen on GnRH receptors and on gonadotrope responsiveness to the decapeptide. P-treatment (4 h) significantly augmented GnRH-receptor concentrations (4.44 +/- 0.6 fmol/10(6) cells) as compared to cells treated only with E (2.6 +/- 0.5 fmol/10(6) cells). Parallel significant changes in GnRH-induced LH secretion were observed. The acute increase in GnRH-receptor number was nearly maximal (180% of receptor number in cells treated with E alone) within 30 min of P addition. Chronic P-treatment (48 h) significantly reduced pituitary responsiveness to GnRH as compared to E-treatment. The GnRH-receptor concentrations (3.9 +/- 0.6 fmol/10(6) cells), however, remained elevated above those in E-primed cells. GnRH-receptor affinity was not influenced by any of the different treatments. These results indicate that the acute facilitatory P-effect on GnRH-induced LH release is at least chronologically closely related to an increase in GnRH-receptor concentration. The chronic negative P-effect on pituitary responsiveness to GnRH, however, shows no relation to changes in available GnRH receptors.

Animals↗
PubMed1990

Weak estrogenic activity of phenol red in the pituitary gonadotroph: re-evaluation of estrogen and antiestrogen effects.

Phenol Red (Phr) which is widely used as a pH indicator in cell culture media has recently been described to possess estrogenic activity in different cell types. In the present study we investigated if the dye shows such activity on LH secretion of cultivated rat pituitary cells and controlled the established effects of estradiol (E2) and keoxifene (K) in this model in the absence of Phenol Red. 24 h treatment of pituitary cell cultures with Phr led to enhancement of GnRH-stimulated LH secretion whereas 4 h treatment reduced LH secretion. When the cells received E2 instead of Phr for the indicated incubation periods we observed nearly identical results i.e. a short-term inhibitory and a long-term stimulatory effect on LH secretion. 24 h treatment of pituitary cell cultures with increasing concentrations of Phr led to a stimulatory effect on GnRH-stimulated LH secretion an effect that occurred at 10 microM got maximal at 100 microM and was lost at higher concentrations resulting in a bell-shaped dose-response curve. The inhibitory action of Phr was present at concentrations greater than or equal to 10 microM. Both effects could be blocked by the antiestrogen K indicating their specificity. K has recently been described to induce an antigonadotrophic effect in this model. Although high concentrations of the antiestrogen were still able to inhibit LH secretion this effect was not present at lower concentrations when Phr-free culture medium was used in the experiments. Thus Phr showed weak estrogenic activity in the gonadotroph. The established actions of E2 and K on LH secretion were qualitatively reproducible when Phr was excluded from the culture medium.

Animals↗
PubMed1990

The gene for the ubiquitous octamer-binding protein Oct-1 is on human chromosome 1, region cen-q32, and near Ly-22 and Ltw-4 on mouse chromosome 1.

Oct-1 is a sequence-specific transcription and DNA replication factor that recognizes the octameric sequence ATGCAAAT. This protein shares an extended region of sequence similarity, called the POU domain, with the lymphoid-specific transcription factor Oct-2, the pituitary-specific transcription factor Pit-1, and the Caenorhabditis elegans cell lineage gene product unc-86. Two subdomains, POU-related homeobox and POU-specific box, lie within the POU domain. Unlike other POU or homeodomain proteins, Oct-1 is ubiquitously expressed. A ubiquitous 95- to 100-kDa protein that has the same DNA-binding properties and is variously referred to as OTF-1, NFIII, or OBP100 is probably identical to Oct-1. The human gene was mapped by Southern blot analyses of human x rodent hybrid cell lines to chromosome 1, region cen-q32. In Chinese hamster x mouse hybrid cell lines the mouse locus was also mapped to chromosome 1. With the BXD (from progenitor strains C57BL/6J and DBA/2J) set of recombinant inbred strains of mice, the murine gene was localized on the linkage map of mouse chromosome 1. There were no recombinants among 26 strains with Ly-22 and 1 recombinant among 24 strains with Ltw-4. The gene symbol is OTF1 for humans and Oct-1 for mouse.

Animals↗
PubMed1989

Gonadotropin releasing hormone binding sites in human epithelial ovarian carcinomata.

As a first step to investigate whether gonadotropin releasing hormone (GnRH) analogs might be able to modulate directly the proliferation of human epithelial ovarian carcinomata, we checked if binding sites for GnRH are present in these malignancies. Specific binding of [125I][D-Ala6-des Gly10]-GnRH-ethylamide (GnRH agonist = GnRH-A) could be demonstrated in plasma membranes from 32 out of 40 ovarian carcinomata tested. This binding was dependent on temperature, time and plasma membrane concentration. Mathematical analysis of the binding data showed that the interaction of GnRH-A with the binding sites was consistent with a single class of low affinity, high capacity binding sites (Ka = 1.42 +/- 0.14 X 10(5) M-1; range: 0.3-3.8 X 10(5) M-1; R = 209 +/- 69 X 10(-12) M/mg membrane protein; range 16-400 X 10(-12) M/mg MP; means +/- S.E., n = 32). Native GnRH and the GnRH antagonist [D-p-Glu1, D-Phe2, D-Trp3,6]-GnRH had Ka values comparable to those of the GnRH-A used. [125I]GnRH-A binding could not be displaced by oxytocin, thyrotropin releasing hormone and corticotropin releasing factor in concentrations up to 10(-4) M. Somatostatin cross-reacted with binding sites from some carcinomata, while it did not displace GnRH-A binding in membranes from others. Though the functional role of this specific binding site for GnRH in human epithelial ovarian carcinomata is still obscure, it might be part of an autocrine regulatory system and provide a possible point of attack for therapeutic approaches using GnRH analogs in this malignancy.

Adenocarcinoma↗
PubMed1989

Studies on the subcellular mechanisms mediating the negative estradiol effect on GnRH-induced LH-release by rat pituitary cells in culture.

Cultured pituitary cells from adult female rats were treated for 4 or 24 h in the absence or presence of E2 (10(-9) mol/l) with increasing concentrations of the transcription inhibitor actinomycin-D or the translation inhibitor puromycin. During the last 4 h of incubation, LH release was stimulated with 5 X 10(-10) mol/l GnRH. The positive E2 effect observed after 24 h treatment with the steroid was clearly abolished by actinomycin-D at concentrations greater than or equal to 10(-10) mol/l and by puromycin at concentrations greater than or equal to 10(-5) mol/l. These findings indicate that the positive E2 effect on GnRH-induced LH release is fully dependent on intact mRNA and protein synthesis. The negative E2 effect observed after 4 h treatment with the steroid was not affected by actinomycin-D and abolished by puromycin only at concentrations greater than or equal to 10(-4) mol/l. Similar results were obtained, when cells had been treated for 4 h with actinomycin-D or puromycin before the 4 h E2 treatment started. Thus, the negative E2 effect seems to be independent of mRNA synthesis and dependent on protein synthesis to a lesser extent than the positive E2 effect. In an attempt to identify positively the subcellular mechanism via which E2 exerts its negative effect, several steps in the GnRH stimulus secretion coupling mechanism were checked whether or not they are modulated by E2. The negative effects of E2 (10(-9) mol/l) on LH release induced by GnRH (10(-10), 10(-9) mol/l) and by the activators of voltage dependent Ca2+ channels K+ (64 mmol/l) or veratridine (3.3 X 10(-5) mol/l) were comparable to those of the calcium antagonist verapamil (10(-6) mol/l). These findings supported the speculation that E2 might act on the Ca2+ channels. The LH release induced by the Ca2+ ionophores A 23 187 (10(-4) mol/l) or ionomycin (6.6 X 10(-5) mol/l), however, was also significantly reduced by 10(-9) mol/l E2, indicating that the steroid modulated a mechanism secondary to the increase of intracellular Ca2+. Also GnRH (10(-9), 10(-8) mol/l) induced accumulation of [3H]inositol phosphates was not influenced by E2 (10(-9) mol/l) treatment, though the steroid exerted a significant negative effect on the LH release by these cells, indicating that phosphatidylinositol-4,5-biphosphate breakdown is not the point of attack for the estrogen.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Modulation of gonadotropin-releasing hormone receptor concentration in cultured female rat pituitary cells by estradiol treatment.

Short-term (0.5-4 h) treatment of rat pituitary cells in culture with estradiol (E2) results in a significant decrease of Gonadotropin-Releasing Hormone (GnRH) induced LH-release. We studied whether changes in the concentrations of GnRH-receptors (GnRH-R) might account for this phenomenon: pituitary cells from adult female rats were incubated for 4 or 24 h in the presence or absence of 10(-9) M E2. Then saturation curves of D-Ala6-des-Gly10-GnRH ethylamide binding were obtained. In addition, binding studies were carried out in cultures incubated for 0.5, 1, 2 or 4 h with or without 10(-9) M E2 using a near saturating concentration of GnRH-analog. No changes of GnRH-R affinity occurred (4 h experiments: Ka in vehicle treated cells: 0.94 +/- 0.2 x 10(9) M-1, Ka in E2 treated cells: 1.06 +/- 0.3 x 10(9) M-1; 24 h experiments: Ka vehicle: 0.95 +/- 0.2 x 10(9) M-1, Ka E2: 0.82 +/- 0.3 x 10(9) M-1). The GnRH-R concentrations, however, were significantly reduced (44 +/- 3%; P less than 0.001) by 4 h E2 treatment and increased (by 68 +/- 8%; P less than 0.01) by 24 h of E2 treatment. The GnRH induced LH-release in aliquots of the same cell preparations was significantly reduced after 4 h and markedly increased after 24 h of E2 treatment. The experiments on the time-course of the reduction of D-Ala6-GnRH-binding by E2 treatment showed that the number of GnRH-R was significantly decreased (24 +/- 1%; P less than 0.05) already after 0.5 h of exposure to the estrogen. This is also the time period after which the negative E2-effect on GnRH-induced LH-release becomes significant. These data provide first evidence that the short-term negative E2-effect on GnRH induced LH-release by rat pituitary cells in culture could be mediated via a reduction of available GnRH-R.

Animals↗
PubMed1988

OBP100 binds remarkably degenerate octamer motifs through specific interactions with flanking sequences.

We have used the 100-kD HeLa cell octamer-binding protein OBP100 as a model to study flexible DNA sequence recognition by promoter-binding proteins. OBP100 binds to the conserved octamer motif ATGCAAAT found in numerous promoters and additionally to two degenerate octamer motifs (sites I and II) within the SV40 enhancer region. We show here that OBP100 binds the herpes simplex virus immediate early promoter TAATGARAT (R = purine) motif itself, extending the flexibility of OBP100 sequence recognition to sequences that bear very little resemblance (four matches over a 14-bp region). Nevertheless, a progression of OBP100-binding sites can be established that links the sequences of these two apparently unrelated binding sites by incremental steps. Mutational and chemical modification interference analyses of a degenerate octamer binding site (SV40 site II) show that specific sequences, which are not normally conserved but flank the degenerate octamer motif, can compensate for the degeneracy in the octamer core sequence. Thus, different regions of the binding site sequence (core or flanking) can diverge separately but not independently of one another. These results suggest that flexible DNA sequence recognition arises because there are few obligatory contact sites for OBP100 binding, but, rather, specific binding reflects the sum of many independent interactions.

Animals↗
PubMed1987

A 100-kD HeLa cell octamer binding protein (OBP100) interacts differently with two separate octamer-related sequences within the SV40 enhancer.

Numerous eukaryotic upstream promoter and enhancer regions contain a functional octamer sequence ATGCAAAT. We have examined the interactions between an octamer binding protein isolated from HeLa cells and the SV40 and immunoglobulin heavy-chain (IgH) gene enhancers. A partially purified octamer binding activity forms a single complex with the IgH enhancer octamer in a gel retardation assay, but two complexes with a SV40 enhancer fragment containing a single 72-bp element. By using point mutants and both dimethyl sulfate and diethyl pyrocarbonate modification interference assays, we show that the SV40 complexes result from binding of a factor to the octamer-related sequence ATGCAAAG (Octa1) and to an adjacent previously unidentified octamer-related sequence ATGCATCT (Octa2). The base-specific interactions with Octa1 and Octa2 differ; chemical modifications over a 10-bp sequence TATGCAAAGC affect Octa1 binding whereas Octa2 binding is affected by modifications spanning a 13-bp sequence ATGCATCTCAATT in which the octamer-like sequence is not centered. The octamer binding activity has been purified extensively by a DNA affinity precipitation procedure and SDS-polyacrylamide gel electrophoresis. The purified protein, OBP100, has an apparent molecular weight of 100 kD and binds both SV40 Octa1 and Octa2, as well as the IgH enhancer. The distinct interactions of OBP100 with the differently sized Octa1 and Octa2 binding sites suggest remarkably flexible sequence recognition between OBP100 and its binding sites.

Base Sequence↗
PubMed1986

Mutagenesis of conserved 5' elements and transcription of a chicken H1 histone gene.

In addition to readily identifiable TATA and CAAT boxes, chicken H1 histone genes contain a highly conserved G-rich region at about minus 80 and an A-rich H1 histone gene-specific motif some 120 bases upstream from the H1 mRNA cap site. The level of transcription from wild-type, 'G-box' and 'A-box' H1 deletion mutant templates was tested in Xenopus oocytes and in HeLa cells. Removal of the H1 gene-specific motif had no effect on H1 gene transcription in either assay system, whereas deletion of the G-rich sequence decreased H1 mRNA levels by about ten-fold in oocytes and in HeLa cells. At least in heterologous systems, the H1-gene specific A-rich region does not appear to influence the level of H1 gene transcription.

Animals↗
PubMed1981

Pediatric Legionnaires' disease: diagnosis by direct immunofluorescent staining of sputum.

Legionnaires' disease occurred in a 3-year-old boy with Down's syndrome. His illness was characterized by bilateral pneumonia, high fever, and response to erythromycin. The diagnosis was made by demonstrating Legionella pneumophila, serogroup 1, in sputum with a direct fluorescent antibody stain. L pneumophila antigen was detected in urine by an enzyme-linked immunospecific assay. The diagnosis was confirmed by a more than fourfold rise in serum antibody titer. Although Legionnaires' disease appears to be uncommon in children, it should be included in the differential diagnosis of pneumonia in the immunocompromised child.

Antibodies, Bacterial↗