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Biomedical subjects

L Miller

Publications and source records attributed to L Miller.

At least 109 records · Page 6Linked to original sources

Female steroid hormones regulate production of pro-inflammatory molecules in uterine leukocytes.

Estrogens and progesterone could be among the environmental signals that govern uterine immune cell synthesis of pro-inflammatory substances. In order to investigate this possibility, we first mapped expression of the inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) genes in the leukocytes of cycling and pregnant mouse uteri, then tested the ability of estradiol-17 beta (E2) and progesterone to influence gene expression. Immunohistochemistry, in situ hybridization, and other experimental approaches, revealed that the iNOS and TNF-alpha genes are expressed in mouse uterine mast cells, macrophages and natural killer cells (uNK). Gene expression in each cell type was noted to be dependent upon stage of the cycle or stage of gestation, implying potential relationships with levels of female hormones and state of cell differentiation or activation. Further in vivo and in vitro experiments showed that individual hormones have cell type-specific effects on synthesis of iNOS and TNF-alpha that are exerted at the level of transcription. In uterine mast cells, iNOS and TNF-alpha are promoted by E2 whereas preliminary studies in macrophages suggest that transcription and translation of the two genes are unaffected by E2 but are inhibited by progesterone. Uterine NK cell production of iNOS and TNF-alpha is strongly related to cell differentiation, which is initiated and sustained by progesterone. Collectively, the results indicate that regulation of synthesis of pro-inflammatory molecules by hematopoietic cells in cycling and pregnant uterus comprises a new and potentially critical role for female steroid hormones.

Animals↗

Fas ligand is positioned in mouse uterus and placenta to prevent trafficking of activated leukocytes between the mother and the conceptus.

Despite intimate juxtaposition of maternal and fetal tissues during mammalian pregnancy, reciprocal migration of cells is limited. To evaluate the postulate that cell traffic is restricted by expression of Fas ligand (FasL) in the uterus and placenta, FasL mRNA was identified by using reverse transcription-PCR, and FasL protein was identified by Western blotting and immunohistology. FasL mRNA and protein were detected at all stages tested (gestation days (g.d.) 6-18). At g.d. 6 to 10, immunoreactive FasL was prominent in glandular epithelial cells and decidual cells. Between g.d. 12 and 14, expression shifted to placental trophoblast cells bordering maternal blood spaces and fetal placental endothelial cells. Thus, FasL is appropriately positioned, first in the uterus and then in the placenta, to deter trafficking of activated Fas+ immune cells between the mother and the fetus. To test whether the absence of functional FasL affects pregnancy, uteroplacental units from homozygous matings of gld mice, a mutant strain lacking functional FasL, were examined. Extensive leukocytic infiltrates and necrosis at the decidual-placental interface were observed from day 10 onward, resorption sites were common, and small litters were delivered by gld mice. These observations are consistent with the idea that FasL at the maternal-fetal interface protects the placenta against a maternal leukocytic influx that reduces fertility.

Animals↗

In vivo footprints are found in the Xenopus 63 kDa keratin gene promoter prior to the appearance of mRNA.

Previous work on the promoter region of the 63 kDa keratin gene demonstrated that in vivo footprints did not change during the transition from low-level to high-level transcription. Reverse transcription polymerase chain reaction and in vivo footprinting were used to determine if these DNA-protein interactions are present before transcription begins. The results presented indicate that during development, DNA-protein interactions are present in the promoter region of the 63 kDa keratin gene at stage 44, four days prior to the initial appearance of 63 kDa keratin mRNA, at stage 48. Thus, the occupancy of these sites at stage 44 is not sufficient for transcription, but may have a role in 'poising' the keratin promoter for the initiation of epidermal-specific transcription. The results suggest that the developmental history of a gene may be important in regulating its temporal and spatial expression.

Animals↗

Expressions of anxiety in African Americans: ethnography and the epidemiological catchment area studies.

High levels of anxiety have long been reported for African Americans. Recent analyses of Epidemiological Catchment Area (ECA) data have failed to support this, although contemporary ethnographies have discussed important African American folk idioms of anxiety. This study compares ethnographically reported symptoms of anxiety in African Americans to those reported in the ECA data. A multivariate analysis of female African American and European American differences in comparable ECA and ethnographic symptoms was performed. Significant differences were found not in ethnicity but in education levels. Alternative interpretations are discussed. Methodological problems are discussed highlighting limitations of both household survey research, such as the ECA project, and ethnography.

Black or African American↗

Implementing assertive community treatment programs in rural settings.

The authors present a controlled evaluation of a rural adaptation of the assertive community treatment (ACT) model for clients with serious and persistent mental illness (SPMI). Four community mental health settings adopted an ACT model, while a fifth site blended ACT principles with those of the Rhinelander model, another approach to case management for persons with SPMI. A broad array of client and system outcomes were evaluated at 6, 12, and 24 months into the intervention. Twelve-month findings alerted us to potential problems in implementing the treatment model in study year 1; the implementation was qualitatively evaluated and weaknesses were addressed at the beginning of the second treatment year. Small, positive findings at 24 months suggested that the mid-study course correction may have had an impact. We present these findings along with descriptive data on the challenges of implementing complex services models. We give particular attention to describing implementation barriers to mental health services provision that are uniquely rural.

Adult↗

Freud and consciousness: the first one hundred years of neuropsychodynamics in theory and clinical practice.

Psychoanalysis emerged out of Freud's neuropsychologic studies of consciousness and cognition. This article describes the historical development of neuropsychodynamic theories of consciousness and personality, and traces their application to several neuropsychiatric syndromes of intense contemporary clinical interest. Even in this era of narrow syndromic differentiation and classification, an appeal is made for a more integrated approach to the evaluation and treatment of neurobehavioral syndromes.

Consciousness↗

Expression of the inducible nitric oxide synthase gene in mouse uterine leukocytes and potential relationships with uterine function during pregnancy.

Nitric oxide (NO), a potent and versatile free radical, is synthesized in leukocytes by the inducible form of NO synthase (iNOS). In this study, leukocytes in pregnant mouse uterus were investigated for expression of the iNOS gene. Inducible NOS mRNA, which was identified by reverse transcriptase polymerase chain reaction, was high relative to an invariant mRNA, glyceraldehyde-3-phosphate dehydrogenase, in midgestation uteri (gestation days [g.d.] 10, 12, and 14) but was low in late-gestation uteri (g.d. 16 and 18). Inducible NOS protein, identified immunohistochemically in paraformaldehyde-fixed uteri taken from g.d. 6 through 18 using rabbit antibodies generated to mouse carboxyl terminus iNOS peptides, was prominent in a few myometrial mast cells at early stages and was strongly expressed from g.d. 6 through g.d. 14 in myometrial macrophage-like cells. Inducible NOS protein was first detected in uterine (u) natural killer (NK) cells at g.d. 8. Signals peaked in this lineage at g.d. 10 and declined thereafter. Uterine leukocytes cultured in vitro expressed the iNOS gene; a hybridoma cell line derived from mouse uNK cells (GWM1-2) contained iNOS mRNA, and cells migrating from mouse metrial gland explants included iNOS/ leukocytes. Large, granular iNOS + uNK cells were absent from the uteri of homologously mated pregnant TgE26 mice, an NK cell-deficient transgenic mouse strain, but immunoreactive iNOS was detectable in trophoblast, a cell lineage that did not contain immunoreactive iNOS in NK cell-competent Swiss-Webster mice. In TgE26 mothers gestating normal embryos, the same pattern was observed. Collectively, the results of this study demonstrate that iNOS is present in mouse uterine leukocytes including mast cells, macrophage-like cells, and uNK cells, and suggest that in the absence of uNK cells, the placenta synthesizes iNOS. These findings are consistent with the postulate that leukocyte NO contributes importantly to events associated with successful pregnancy that are likely to include relaxation of vascular smooth muscle.

Animals↗

Intergenerational transmission of parental bonding among women.

OBJECTIVE: To examine the transmission of parental bonding style from mothers to daughters. METHOD: Sixty mothers and their 69 daughters were independently assessed over the course of a 10-year follow-up. The Parental Bonding instrument was administered to both mothers and daughters to assess their own childhood parenting. Depression was assessed using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. Temperament was assessed through self-report on the Dimensions of Temperament Survey. A series of logistic regressions were run to predict daughter report of maternal affectionless control, taking into account maternal and daughter depression status, temperament, and socioeconomic status. RESULTS: The intergenerational transmission of parental bonding among women was shown to be independent of maternal depression, daughter depression, maternal temperament, daughter temperament, and socioeconomic status. CONCLUSION: Given the previously established association between parental bonding style and depression in offspring, the sturdiness of the intergenerational transmission of parental bonding among women suggests the routine clinical assessment of maternal bonding style.

Adolescent↗

Religiosity and depression: ten-year follow-up of depressed mothers and offspring.

OBJECTIVE: This study examines maternal religiosity as a protective factor against depression in offspring. METHOD: Sixty mothers and 151 offspring were independently assessed over the course of a 10-year follow-up. Maternal and offspring religiosity were assessed on the basis of self-report of the importance of religion, the frequency of attendance of religious services, and religious denomination. Depression was assessed using the Schedule for Affective Disorders-Lifetime version. Maternal bonding style was assessed through offspring report on the Parental Bonding Instrument. A series of logistic regressions were run to predict offspring depression status, taking into account maternal religiosity, offspring religiosity, and mother-offspring concordance of religiosity. RESULTS: Maternal religiosity and mother-offspring concordance of religiosity were shown to be protective against offspring depression, independent of maternal parental bonding, maternal social functioning, and maternal demographics. CONCLUSION: Maternal religiosity and offspring concordance with it may protect against depression in offspring.

Adult↗

Erosive adenomatosis of the nipple: a benign imitator of malignant breast disease.

We present the case of a 66-year-old white woman with erosive adenomatosis of the nipple, in which an initial diagnosis of Paget's disease was considered. Diagnosis of erosive adenomatosis of the nipple was made by the characteristic histologic findings on a biopsy specimen. This essentially benign condition is generally unilateral, with erythema, crusting, and hardening of the nipple. Histologic findings of erosive adenomatosis of the nipple eliminate the diagnosis of invasive carcinoma or Paget's disease, which can have clinical features similar to those of erosive adenomatosis of the nipple.

Adenoma↗

Renal function in cardiac transplant recipients: retrospective analysis of 133 consecutive patients in a single center.

We retrospectively studied 133 consecutive cardiac transplant patients who had lived more than 5 months post-transplantation. All patients had received a cyclosporine (CyA) based triple immunosuppressive protocol. Mean (+/- SE) duration of follow-up was 32 +/- 1.8 months (range 5-60 months). Serial mean serum creatinine significantly increased from 1.26 +/- 0.025 mg/dl at 1-2 months post-transplant to 1.4 +/- 0.05 at 3 months, 1.48 +/- 0.03 at 6 months, and 1.55 +/- 0.04 at 9 months with a subsequent plateau in serum creatinine levels up to 60 months of follow-up, at which point it had reached 1.66 +/- 0.1 mg/dl. The reciprocal creatinine (1/Cr) curve also showed a biphasic decline in renal function, with a rapid decline in the first 6 months followed by no further decline up to 60 months of follow-up. Approximately 4% of the patients at 1-2 months, 8% at 3 months, and 12-17% at 6-60 months had serum creatinine > and = 2.0 mg/dl. None of the patients developed end-stage renal disease requiring dialysis. At all time points, patients with serum creatinines > and = 2.0 mg/dl received a lower CyA dose than those with serum creatinines < 2.0 mg/dl (3.1 +/- 0.1 vs. 4.0 +/- 0.1 mg/kg/d, respectively, p < 0.0001), suggesting that the CyA dose had been appropriately reduced in response to a rise in serum creatinine. There was no significant rise in serum potassium (4.4 +/- 0.04 vs. 4.5 +/- 0.1 meq/l, 1-2 vs. 60 months, respectively, p = NS) or serum cholesterol (205.5 +/- 4.1 vs. 211 +/- 6.5 mg/dl, 1-2 vs. 60 months, respectively, p = NS). However, there was a significant rise in systolic (134 +/- 1.5 vs. 140.5 +/- 2.7 mmHg, p < 0.05), diastolic (84 +/- 1.0 vs. 90 +/- 2.1 mmHg, p < 0.05), and mean arterial (101 +/- 1.0 vs. 107 +/- 2.1 mmHg, p<0.05) pressures at 1-2 vs. 60 months. Serum trough CyA levels and CyA doses were significantly reduced over the follow-up period (174 +/- 6.7 vs 110.5 +/- 12.5 ng/ml, and 4.4 +/- 0.1 vs. 2.5 +/- 0.2 mg/kg/d, at 1-2 vs. 60 months, respectively, p < 0.05). At 1 yr, 56% of the patients were treated with antihypertensive medications (predominately calcium channel blockers) and 14% received lipid lowering medications (predominately an HMG-CoA reductase). We conclude, after an initial rise in serum creatinine and decline in 1/Cr curve, during the first 6-9 months post-cardiac transplant, renal function remains stable up to 5 yr of follow-up, if serum CyA levels and CyA doses are monitored and adjusted closely. However, we cannot rule out the possibility of subclinical progressive histopathologic changes, due to chronic CyA nephrotoxicity, which could become clinically apparent after a longer duration of follow-up.

Blood Pressure↗

[Evaluation of the dynamics of in-group strain during long-term isolation].

Evaluation of the dynamics of in-group strain was conducted with conjunction with the 90-day modelling of space flight (ECOPSY-95). Baseline were the data of sociometric testing and analysis of video records of movements and behavior of the main and visiting crews (three members in each). Global assessment of the in-group strain was made on integration of experimental data using the Czech procedure of interdisciplinary approach to description of a social system, and the theory of fuzzy aggregate. The procedure allows to visualize interpersonal relations as social maps. Reaction to the psychoemotional strain stemmed from long stay in isolation was manifested by gradual build-up of interpersonal strain, redistribution of the functional/role structure of the crew, destabilization of in-group interactions and its split.

Adult↗

Autotransplants in multiple myeloma: what have we learned?

Of 496 consecutive patients with multiple myeloma (MM) enrolled in clinical trials of tandem transplants with peripheral blood stem cells support, 470 (95%) completed the first autotransplant with melphalan 200 mg/m2 (MEL 200) and 363 (73%) completed the second transplant with either MEL 200 (40%), MEL 140 mg/m2 (MEL 140) with total-body irradiation (17%), or a combination of alkylating agents (16%), depending on the response status prior to the second transplant; 31 patients up to age 60 years received an allograft as the second transplant. The median interval from first to second transplant was 5 months. Treatment-related mortality during the first year after transplantation was 7%, and complete remission (CR) was obtained in 36%; the median durations of event-free survival (EFS) and overall survival (OS) after transplant were 26 and 41 months, respectively. Low beta 2-microglobulin ([B2M] < or = 2.5 mg/L) and C-reactive protein ([CRP] < or = 0.4 mg/dL) were the most significant standard parameters associated with both prolonged EFS and OS. Median OS exceeded 5.5 years in the one third of patients with both low B2M and CRP. When cytogenetics were included in the analysis, the presence of 11q abnormalities and/or complete or partial deletion of chromosome 13 ("unfavorable karyotype") became a dominant negative feature for both EFS and OS. In addition to these pretransplant parameters, attainment of CR and application of two transplants within 6 months both significantly extended EFS and OS. The group of patients (7%) with high B2M and CRP with either IgA isotype or unfavorable karyotype had the worst prognosis (EFS, < or = 10 months; median OS, < or = 12 months) and will require novel therapy. We conclude that tandem transplants are feasible in the majority of patients up to age 70 years, effecting CR in one third of all patients. Median OS was greater than 5.5 years, regardless of pretransplant features, if the first transplant was applied within 12 months of initial treatment and the second transplant no more than 6 months later.

Adult↗