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Biomedical subjects

L C Miller

Publications and source records attributed to L C Miller.

At least 19 recordsLinked to original sources
PubMed2006

Norepinephrine transporter-deficient mice respond to anxiety producing and fearful environments with bradycardia and hypotension.

The study of anxiety and fear involves complex interrelationships between psychiatry and the autonomic nervous system. Altered noradrenergic signaling is linked to certain types of depression and anxiety disorders, and treatment often includes specific transporter blockade. The norepinephrine transporter is crucial in limiting catecholaminergic signaling. Norepinephrine transporter-deficient mice have increased circulating catecholamines and elevated heart rate and blood pressure. We hypothesized, therefore, that reduced norepinephrine clearance would heighten the autonomic cardiovascular response to anxiety and fear. In separate experiments, norepinephrine transporter-deficient (norepinephrine transporter-/-) mice underwent tactile startle and trace fear conditioning to measure hemodynamic responses. A dramatic tachycardia was observed in norepinephrine transporter-/- mice compared with controls following both airpuff or footshock stimuli, and pressure changes were also greater. Interestingly, in contrast to normally elevated home cage levels in norepinephrine transporter-deficient mice, prestimulus heart rate and blood pressure were actually higher in norepinephrine transporter+/+ animals throughout behavioral testing. Upon placement in the behavioral chamber, norepinephrine transporter-deficient mice demonstrated a notable bradycardia and depressor effect that was more pronounced in females. Power spectral analysis indicated an increase in low frequency oscillations of heart rate variability; in mice, suggesting increased parasympathetic tone. Finally, norepinephrine transporter-/- mice exhibited sexual dimorphism in freeze behavior, which was greatest in females. Therefore, while reduced catecholamine clearance amplifies immediate cardiovascular responses to anxiety- or fear-inducing stimuli in norepinephrine transporter-/- mice, norepinephrine transporter deficiency apparently prevents protracted hemodynamic escalation in a fearful environment. Conceivably, chronic norepinephrine transporter blockade with transporter-specific drugs might attenuate recognition of autonomic and somatic distress signals in individuals with anxiety disorders, possibly lessening their behavioral reactivity, and reducing the cardiovascular risk factors associated with persistent emotional arousal.

Animals↗
PubMed2004

Interferon type I response in porcine reproductive and respiratory syndrome virus-infected MARC-145 cells.

Infection by porcine reproductive and respiratory syndrome virus (PRRSV) results in a weak induction of the innate immune response. There are many genes that collectively comprise this response and the extent to which each gene responds to PRRSV infection is unclear and warrants further investigation. To this end, we have utilized real-time PCR using SYBR Green I dye-based detection to quantify transcript abundance of the type I interferons (IFN-alpha and -beta) and IFN-beta transcriptional enhanceasome genes. In MARC-145 cells, both IFN-alpha and -beta transcript abundance were unaffected by PRRSV infection. However, stimulation of MARC-145 cells by exogenous double-stranded RNA, resulted in significant increases in transcript abundance of both IFN-alpha and -beta as well as IFN-beta enhanceasome components, indicating that a type I IFN response could be induced in these cells. The double-stranded RNA induction of type I IFN transcription was significantly inhibited by dual-exposure with PRRSV. These results suggest that PRRSV infection directly interferes with type I IFN transcriptional activation early in its pathway, at the level of IFN-beta gene transcription.

Animals↗
PubMed2001

Role of the cytoplasmic domain of the beta-subunit of integrin alpha(v)beta6 in infection by foot-and-mouth disease virus.

Field isolates of foot-and-mouth disease virus (FMDV) are believed to use RGD-dependent integrins as cellular receptors in vivo. Using SW480 cell transfectants, we have recently established that one such integrin, alpha(v)beta6, functions as a receptor for FMDV. This integrin was shown to function as a receptor for virus attachment. However, it was not known if the alpha(v)beta6 receptor itself participated in the events that follow virus binding to the host cell. In the present study, we investigated the effects of various deletion mutations in the beta6 cytoplasmic domain on infection. Our results show that although loss of the beta6 cytoplasmic domain has little effect on virus binding, this domain is essential for infection, indicating a critical role in postattachment events. The importance of endosomal acidification in alpha(v)beta6-mediated infection was confirmed by experiments showing that infection could be blocked by concanamycin A, a specific inhibitor of the vacuolar ATPase.

Acids↗
PubMed2001

Preferences about the characteristics of future HIV prevention products among men who have sex with men.

This study of men who have sex with men (MSM) examined preferences about the characteristics of a potential product for preventing sexual transmission of HIV, such as a rectal microbicide. MSM were recruited in West Hollywood, California. They self-administered a questionnaire and rated 48 product characteristics representing seven dimensions. Overall, the ratings were highest for effectiveness in preventing HIV and other sexually transmitted diseases, followed by characteristics reflecting the physical or secondary effects of the product and logistics of use. Physical attributes, convenience/accessibility, and psychological aspects had intermediate ratings; interpersonal dynamics had the lowest rating. Men with negative attitudes about using condoms to prevent HIV infection were more likely than their counterparts to prefer a product that does not reduce sexual sensation or pleasure, does not break the mood, and can be used after a sexual encounter ends. A similar pattern was observed when participants were stratified by whether or not they had engaged in unprotected anal intercourse in the past 12 months. The findings inform the development, testing, and marketing of a future HIV prevention product for MSM.

Adult↗
PubMed2000

Health of children adopted from China.

OBJECTIVE: Since 1989, American parents have adopted 18 846 Chinese children. This study assesses the health and developmental status of these children after their arrival in the United States. PATIENTS AND METHODS: A total of 452 children (443 girls) in 2 groups were evaluated. The clinic group children (n = 192) included all Chinese adoptees seen in an international adoption clinic between 1991 and 1998. The travel group comprised 260 of 325 Chinese children placed by a single Massachusetts adoption agency between 1991 and 1996 whose adoptive parents and American physicians responded to mailed questionnaires. One hundred ninety-one of the travel group children were cared for by 1 of us (N.W.H.) during the adoption process in China. RESULTS: Growth and developmental delays were frequent in the clinic group. Z scores </=-2 were found in 39% of children for height, 18% for weight, and 24% for head circumference. The duration of orphanage confinement was inversely proportional to the linear height lag (r =.9), with a loss of 1 month of height age for every 2. 86 months in the orphanage. Of the children, 75% had significant developmental delay in at least 1 domain: gross motor in 55%, fine motor in 49%, cognitive in 32%, language in 43%, social-emotional in 28%, activities of daily living in 30%, and global delays in 44%. The incidence of medical problems was similar in both groups of children (travel group and clinic group). Overall, among the 452 children, elevated lead levels were found in 14%, anemia in 35%, abnormal thyroid function tests in 10%, hepatitis B surface antigen in 6%, hepatitis B surface antibody in 22%, intestinal parasites (usually Giardia) in 9%, and positive skin test results for tuberculosis in 3.5%. One child each had hepatitis C exposure and congenital syphilis. No child had human immunodeficiency virus infection. Unsuspected significant medical diagnoses, including hearing loss, orthopedic problems, and congenital anomalies, were found in 18% (81/452) of the children. CONCLUSIONS: Chinese adoptees display a similar pattern of growth and developmental delays and medical problems as seen in other groups of internationally adopted children. An exception is the increased incidence of elevated lead levels (overall 14%). Although serious medical and developmental issues were found among the children, overall their condition was better than expected based on recent publicity about conditions in the Chinese orphanages. The long-term outcome of these children remains unknown. China, adoption, orphanage, institutionalized child.

Adoption↗
PubMed2000

Preaching to the choir: preference for female-controlled methods of HIV and sexually transmitted disease prevention.

OBJECTIVES: This study assessed interest in female-controlled methods of HIV and sexually transmitted disease (STD) prevention. METHODS: Surveys were conducted with 168 African American women, aged 18 to 32 years, who had had unprotected sex and at least 3 sexual partners in the last 2 years. RESULTS: Of 44 potential features, "female control" (where women control the method by either wearing or applying it) ranked 22nd in average importance. Women who rated female control as highly important had fewer sex partners and fewer STDs and were more likely to use existing prevention methods frequently. CONCLUSIONS: Female control may be of less interest to women most at risk for HIV and other STDs. This underscores the need to take the priorities and preferences of women into consideration when developing new prevention methods.

Adult↗
PubMed2000

Age-related risk for HIV infection in men who have sex with men: examination of behavioral, relationship, and serostatus variables.

The study examined behavioral, relationship, and serostatus variables that potentially contribute to HIV infection risk in three age groups of men who have sex with men (MSM). MSM recruited in West Hollywood, California self-administered a questionnaire measuring unprotected insertive anal intercourse (UIAI) and unprotected receptive anal intercourse (URAI) with primary and nonprimary partners. The following relationship/serostatus variables were also assessed: recency of HIV testing, knowledge of own HIV serostatus, perception of partner's serostatus, seroconcordance (self and partner seronegative), and self-reported monogamy status. The prevalence of UIAI and URAI was higher with primary than nonprimary partners. These sexual risk behaviors with primary partners were substantially more prevalent among men younger than 25 years of age than among men aged 25 to 30 or over age 30. UIAI and URAI with nonprimary partners were uncommon in each age group, and there were no significant age differences on the serostatus and relationship variables. The findings suggest that young MSM may be at elevated risk for contracting HIV by virtue of their sexual risk behavior with primary partners. Targeted interventions for MSM need to address sexual risk in the context of primary relationships.

AIDS Serodiagnosis↗
PubMed1999

Racial differences in hormone replacement therapy prescriptions.

OBJECTIVE: To examine racial differences in hormone replacement therapy (HRT) use by analyzing the relative risks and rates of HRT prescriptions for black and white women. METHODS: Data on visits to hospital outpatient departments and office-based physicians by black and white women aged 45-64 years were obtained from 25,203 visits sampled in the 1993-1995 National Ambulatory Medical Care Surveys and National Hospital Ambulatory Medical Care Surveys. The relative effect of race on the provision of an HRT prescription at an ambulatory visit was estimated by controlling confounders using logistic regression. Population-based rates of physician visits and visits with HRT prescriptions were also calculated to address issues involving access to care. RESULTS: Approximately 98,787,000 annual visits were made by black and white women 45-64 years of age, 9.2% of which involved prescriptions for HRT. The percentage of visits by black women in which prescriptions for HRT were reported (4.5%) was roughly half that of white women (9.7%). The association persisted after controlling for type of physician, practice type, geographic region, payment source, and non-HRT prescription(s) (odds ratio 2.1; 95% confidence interval 1.5, 2.9). The rate of ambulatory care among black women (3.82 visits per year per woman) was virtually identical to that of white women (3.94 visits per year), whereas the rate of visits with HRT prescriptions for white women was twice as high as for black women (0.38 and 0.17 visits per year, respectively). CONCLUSION: Apparent racial differences in HRT use persist after controlling for physician and visit factors not explored in previous studies.

Black or African American↗
PubMed1999

Soluble adhesion molecules in juvenile rheumatoid arthritis.

OBJECTIVE: To determine serum levels of soluble (s) adhesion molecules in patients with juvenile rheumatoid arthritis (JRA), and to determine whether differences exist in these levels among the 3 subtypes of JRA, and whether levels of these molecules correlate with other measures of disease activity. METHODS: Serum levels of soluble forms of intercellular adhesion molecule-1 (ICAM-1), ICAM-3, vascular (V) CAM-1, L-selectin, and E-selectin were determined by sandwich ELISA in 16 patients with JRA (6 systemic, 6 polyarticular, 4 pauciarticular). Differences in levels among JRA subtypes were determined by ANOVA, and correlations between levels and the following clinical variables were assessed by linear regression analysis: erythrocyte sedimentation rate (ESR), total white blood cell count (WBC), hematocrit (HCT), platelet count (PLT), and total swollen joint count (JC). RESULTS: sE-selectin levels were significantly higher in patients with systemic disease compared to other subtypes (p<0.04). Furthermore, there was a trend toward higher levels of sICAM-1 in systemic disease, which did not reach statistical significance. Significant correlations were found between sE-selectin and ESR (r = 0.68, p<0.006), WBC (r = 0.70, p<0.003), and PLT (r = 0.54, p<0.05) and between sL-selectin and WBC (r = 0.55, p<0.03). CONCLUSION: Because of the small number of patients studied, and the lack of age matched control data, our results must be interpreted with caution. Nonetheless, levels of sE-selectin, and possibly ICAM-1 appear to be relatively elevated in systemic JRA, and may indicate cytokine induction and endothelial cell activation in that subtype. Several molecules, especially sE-selectin, correlate with hematologic variables in JRA. These results suggest that serum levels of these molecules may provide a useful additional marker for disease activity in certain patients.

Adolescent↗
PubMed1998

Infectious causes of arthritis in adolescents.

Although most joint pain in adolescents is secondary to injury, inflammatory arthritis, mechanical problems, and other causes, infectious causes of arthritis should always be considered. Infections may cause arthritis by direct infection, reactive disease, or immune-mediated mechanisms. This chapter reviews common infectious causes of arthritis and also recognizes the difficulties in distinguishing categories.

Adolescent↗
PubMed1998

Fibrin D-dimer as a marker of disease activity in systemic onset juvenile rheumatoid arthritis.

OBJECTIVE: To study the prevalence of coagulation abnormalities in children with systemic juvenile rheumatoid arthritis (JRA) using a sensitive marker of fibrin degradation, and to determine whether serial levels of this variable parallel disease activity or predict response to medications in this disease. METHODS: Levels of d-dimer were determined in 24 consecutive patients with systemic JRA in conjunction with complete blood counts, erythrocyte sedimentation rate, maximum fever, duration of morning stiffness, and swollen joint count. Serial levels were then obtained in 11 patients. Linear regression analyses were done to determine any correlations between d-dimer and the other variables; and paired t test was used to compare levels before and after treatment interventions. Levels of d-dimer were also compared against concurrent clinical events such as pericarditis. RESULTS: Elevated levels of d-dimer were found in 23/24 of the patients (96%). When serial levels were analyzed, there were correlations between levels of d-dimer and fever (p = 0.03) and total leukocyte count (p = 0.04), but not with other variables. There was a significant reduction in levels before and after treatment in patients deemed to be clinical responders to immunomodulatory agents (p = 0.02). Elevated levels were also indicative of severe disease over the remainder of followup; lack of d-dimer indicated a benign disease course. CONCLUSION: With the use of a sensitive and specific marker of fibrinolysis known as d-dimer, coagulation abnormalities were more prevalent in children with systemic JRA than previously reported, and are frequently found during periods of active disease. Furthermore, serial levels of d-dimer appear to parallel response to disease modifying agents, and may predict outcome over a short followup period. Fibrin d-dimer may represent a novel marker that, when used in combination with known variables, could enhance that assessment of disease activity and response to medications in children with systemic onset JRA.

Adolescent↗