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1.
Am J Physiol Cell Physiol ; 309(5): C332-47, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26108665

ABSTRACT

The potent trypanolytic properties of human apolipoprotein L1 (APOL1) can be neutralized by the trypanosome variant surface antigen gene product known as serum resistance-associated protein. However, two common APOL1 haplotypes present uniquely in individuals of West African ancestry each encode APOL1 variants resistant to serum resistance-associated protein, and each confers substantial resistance to human African sleeping sickness. In contrast to the dominantly inherited anti-trypanosomal activity of APOL1, recessive inheritance of these two trypanoprotective APOL1 alleles predisposes to kidney disease. Proposed mechanisms of APOL1 toxicity have included BH3 domain-dependent autophagy and/or ion channel activity. We probed these potential mechanisms by expressing APOL1 in Xenopus laevis oocytes. APOL1 expression in oocytes increased ion permeability and caused profound morphological deterioration (toxicity). Coexpression of BCL2 family members rescued APOL1-associated oocyte toxicity in the order MCL1 ∼ BCLW > BCLXL ∼ BCL2A1 ≫ BCL2. Deletion of nine nominal core BH3 domain residues abolished APOL1-associated toxicity, but missense substitution of the same residues abolished neither oocyte toxicity nor its rescue by coexpressed MCL1. The APOL1 BH3 domain was similarly dispensable for the ability of APOL1 to rescue intact mice from lethal trypanosome challenge. Replacement of most extracellular Na(+) by K(+) also reduced APOL1-associated oocyte toxicity, allowing demonstration of APOL1-associated increases in Ca(2+) and Cl(-) fluxes and oocyte ion currents, which were similarly reduced by MCL1 coexpression. Thus APOL1 toxicity in Xenopus oocytes is BH3-independent, but can nonetheless be rescued by some BCL2 family proteins.


Subject(s)
Apolipoproteins/biosynthesis , Apolipoproteins/toxicity , Lipoproteins, HDL/biosynthesis , Lipoproteins, HDL/toxicity , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Amino Acid Sequence , Animals , Apolipoprotein L1 , Apolipoproteins/genetics , Female , Humans , Lipoproteins, HDL/genetics , Mice , Molecular Sequence Data , Protein Structure, Tertiary/physiology , Proto-Oncogene Proteins c-bcl-2/genetics , Xenopus laevis
2.
Physiotherapy ; 101(1): 75-81, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25280603

ABSTRACT

OBJECTIVE: To evaluate the efficacy of a novel, angular, continuous passive motion device for self-treatment at home in patients with mild-to-moderate, non-specific, chronic low back pain (LBP). DESIGN: Prospective, randomised, waiting-list-controlled (WLC) trial. SETTING: Recruitment and assessment were conducted at the Koren Centre for Physical Therapy. Self-treatment was performed at home. PARTICIPANTS: Thirty-six patients with a score ≤6 on the numeric rating scale (NRS) for pain were enrolled. Twenty-eight patients completed treatment. INTERVENTIONS: Participants were randomised to receive the Kyrobak (Radiancy, Hod-hasharon, Israel) at enrolment [immediate treatment (IT) group] or 3 weeks later (WLC group). Self-treatment was prescribed for 10minutes, one to three times per day, for 3 weeks. The treatment period was followed by a 3-week follow-up period. MAIN OUTCOME MEASURES: Primary outcome was self-reported pain level (NRS). RESULTS: Three weeks of self-treatment with the Kyrobak reduced pain levels significantly in the IT group compared with the WLC group {mean [standard deviation (SD)] ΔNRS score from baseline to post-treatment: IT group, 1.4 (1.5), 95% confidence interval (CI) 0.5 to 2.3; WLC group, -0.1 (2.2), 95% CI -1.1 to 1.2; effect mean difference 1.5}. This benefit was maintained over the follow-up period [from baseline to end of follow-up, mean (SD) ΔNRS score 1.1 (1.8), 95% CI 0.4 to 1.8]. Multi-linear regression analysis found that higher baseline pain resulted in greater pain reduction (P=0.003). Eighty-three percent of participants with a baseline NRS score >4.35 (threshold determined by logistic regression, P=0.01) achieved the minimal important change criterion of ΔNRS score ≥2. Daily NRS score reduced gradually over the treatment period [regression slope -0.052 (0.01), 95% CI -0.07 to -0.03]. CONCLUSIONS: Preliminary evidence suggests that the Kyrobak may be beneficial for short-term relief of non-specific, chronic LBP, particularly in participants with a moderate level of pain. A longer treatment period may lead to a further reduction in pain.


Subject(s)
Electric Stimulation Therapy/instrumentation , Low Back Pain/rehabilitation , Motion Therapy, Continuous Passive/instrumentation , Self Care/instrumentation , Aged , Electric Stimulation Therapy/methods , Equipment Design , Equipment Safety , Female , Follow-Up Studies , Home Care Services , Humans , Israel , Low Back Pain/diagnosis , Male , Middle Aged , Pain Measurement , Patient Satisfaction , Prospective Studies , Severity of Illness Index , Statistics, Nonparametric , Treatment Outcome
3.
Am J Transplant ; 12(7): 1924-8, 2012 Jul.
Article in English | MEDLINE | ID: mdl-22487534

ABSTRACT

Apolipoprotein L-1 (APOL1) gene variants are associated with end-stage renal disease in African Americans (AAs). Here we investigate the impact of recipient APOL1 gene distributions on kidney allograft outcomes. We conducted a retrospective analysis of 119 AA kidney transplant recipients, and found that 58 (48.7%) carried two APOL1 kidney disease risk variants. Contrary to the association seen in native kidney disease, there is no difference in allograft survival at 5-year posttransplant for recipients with high-risk APOL1 genotypes. Thus, we were able to conclude that APOL1 genotypes do not increase risk of allograft loss after kidney transplantations, and carrying 2 APOL1 risk alleles should not be an impediment to transplantation.


Subject(s)
Apolipoproteins/genetics , Black People/genetics , Graft Survival/genetics , Kidney Transplantation , Lipoproteins, HDL/genetics , Adult , Apolipoprotein L1 , Genotype , Humans , Middle Aged
4.
Int J Tuberc Lung Dis ; 15(11): 1522-7, i, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22008767

ABSTRACT

BACKGROUND: Vitamin D increases cathelicidin production, and might alter mortality due to tuberculosis (TB) in human immunodeficiency virus (HIV) coinfection. However, due to abundant sun exposure, vita min D levels might be excellent among Ugandans with HIV and TB. METHODS: We measured 25(OH)D and calcium levels in 50 HIV-negative, 50 HIV-infected and 50 TB-HIV coinfected Ugandan adults. RESULTS: Mean ± standard deviation 25(OH)D levels were 26 ± 7 ng/ml in HIV-negative, 28 ± 11 ng/ml in HIV-infected and 24 ± 11 ng/ml in TB-HIV co-infected adults (P > 0.05 all comparisons). Vitamin D deficiency (< 12 ng/ml) was present in 10% of the HIV-infected subjects, 12% of the TB-HIV co-infected and none of the healthy controls (P = 0.03 for healthy vs. TB, P > 0.05 for other comparisons); 20% of the healthy controls, 22% of the HIV-positive and 38% of the TB-HIV co-infected subjects (P = 0.047 for healthy vs. TB, P > 0.05 for other comparisons) had suboptimal vitamin D levels (< 20 ng/ml). No participant had hypercalcemia. Serum 25(OH)D levels correlated positively with body mass index (r = 0.22, P = 0.03) and serum calcium levels (r = 0.18, P = 0.03). CONCLUSIONS: Ugandan HIV-infected adults with and without TB commonly had suboptimal vitamin D levels. Clinical trials are needed to evaluate the effect of vitamin D on health outcomes in HIV-infected patients with low vitamin D levels.


Subject(s)
AIDS-Related Opportunistic Infections/blood , Calcium/blood , Coinfection/blood , HIV Infections/blood , Tuberculosis/blood , Vitamin D/analogs & derivatives , AIDS-Related Opportunistic Infections/diagnosis , AIDS-Related Opportunistic Infections/epidemiology , Adult , Body Mass Index , Case-Control Studies , Chi-Square Distribution , Coinfection/diagnosis , Coinfection/epidemiology , Cross-Sectional Studies , Female , HIV Infections/diagnosis , HIV Infections/epidemiology , Humans , Male , Middle Aged , Prospective Studies , Sunlight , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Uganda/epidemiology , Vitamin D/blood , Young Adult
5.
J Dermatolog Treat ; 15(6): 360-4, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15764047

ABSTRACT

Numerous preparations that are available for the treatment of psoriasis of the scalp contain high potency steroids, such as betamethasone dipropionate lotion or clobetasol propionate solution. Of special interest is a currently marketed oil preparation that contains the steroid fluocinolone acetonide (0.01%), classified as low potency (Class 6) steroid. Because the combination of emollients in the vehicle base are present to aid in softening the stratum corneum and allow penetration of the steroid component into the lower skin layer, it was thought this preparation would be an efficient treatment for psoriasis of the scalp. This study was designed to demonstrate the efficacy, tolerance and safety of fluocinolone acetonide 0.01% in oil, compared to its vehicle, for the treatment of scalp psoriasis. This was a randomized, double-blind, vehicle-controlled multi-center study in patients with moderate to severe scalp psoriasis. At the completion of the treatment period (21 days) all signs of psoriasis had improved in both treatment groups, the improvements in the FA group being significantly greater compared to those in the vehicle-treated group. The results of the physician global assessments of improvement in the signs of psoriasis from baseline confirmed the findings. Significantly more patients in the FA group had a good or better improvement from baseline compared to the number in the vehicle-treated group. The results of this study conclusively show that FA in an oil base that aids in the softening of the skin and allows penetration of the steroid into the stratum corneum, is an effective treatment for psoriasis of the scalp. This study also showed that the vehicle alone causes an improvement in the signs of psoriasis, but that the addition of 0.1% of the low potency steroid, fluocinolone acetonide, leads to a significantly better improvement.


Subject(s)
Fluocinolone Acetonide/administration & dosage , Glucocorticoids/administration & dosage , Psoriasis/drug therapy , Scalp Dermatoses/drug therapy , Administration, Topical , Double-Blind Method , Female , Humans , Male , Middle Aged , Oils , Pharmaceutical Vehicles
6.
Public Health Rep ; 116(2): 132-47, 2001.
Article in English | MEDLINE | ID: mdl-11847299

ABSTRACT

In the mid-1990s, several state and county public health departments implemented interactive software systems that provided easy access to public health-related data for local boards of health, other public health agencies, health care providers, community groups, and other interested members of the public. Based on their experiences with two well-established state interactive systems and one well-established county system, the authors summarize lessons that could prove useful to state and local public health agencies interested in developing new interactive systems or adapting existing ones. The article addresses issues such as: basing interactive systems on a broad definition of health, designing systems to incorporate user preferences, moving from data warehouses to information warehouses, and fostering prevention communities. Finally, the article provides recommendations to assist federal, state, and local public health agencies in developing the next generation of interactive data access systems.


Subject(s)
Computer Communication Networks , Information Systems , Public Health , User-Computer Interface , Epidemiology , Humans , Massachusetts , Missouri , Program Evaluation , Software , Systems Integration , Washington
7.
Am J Public Health ; 90(11): 1714-9, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11076237

ABSTRACT

OBJECTIVES: This study assessed the impact of the Office of Management and Budget's (OMB's) 1997 revised standards for the collection of race and ethnicity data on state health departments, using the Massachusetts Department of Public Health (MDPH) as the primary example, and we make recommendations for states' implementation of these standards. METHODS: After analyzing the revised OMB standards, existing MDPH data sets were assessed for the impact of the revised standards on data collection, tabulation, analysis, and reporting for state health departments. RESULTS: The revised OMB standards will have an impact on the MDPH and other state health departments. Similarities and differences exist between federal and state health agencies regarding the purpose of data collection, tabulation, analysis, and reporting. These similarities and differences will affect state implementation of the revised OMB standards. CONCLUSIONS: States need to plan for the implementation of the revised OMB standards and to understand the impact of this revision on the collecting and reporting of public health data. The revised OMB standards will introduce added complexities to the collection and analysis of race and ethnicity data, but they will also produce a more nuanced understanding of the relationship of race and ethnicity to the health of the American people.


Subject(s)
Data Collection/methods , Data Collection/standards , Ethnicity/classification , Guideline Adherence/organization & administration , Guidelines as Topic , Needs Assessment/organization & administration , Public Health Practice , Racial Groups/classification , State Government , State Health Plans/organization & administration , Data Interpretation, Statistical , Ethnicity/statistics & numerical data , Humans , Information Systems , Massachusetts , Population Surveillance/methods , United States
8.
Semin Surg Oncol ; 18(3): 259-64, 2000.
Article in English | MEDLINE | ID: mdl-10757892

ABSTRACT

The role of the reconstructive surgeon has increased with an increasingly aggressive surgical approach to locally advanced rectal carcinoma. Multiple options exist for pelvic floor reconstruction. Muscle and myocutaneous flaps for pelvic-floor reconstruction provide well vascularized tissues which may also serve as a biologic spacer. Flaps help to prevent post-radiation fistulae, small bowel obstruction, and pelvic sidewall adherence; flaps also may serve as a barrier to radiation injury. Often a more stable perineal wound closure is achieved. In cases that involve vaginal resection, flaps make neo-vaginal reconstruction possible. Pre-operative consultation with the reconstructive surgeon allows planning of complex, multi-disciplinary procedures, and facilitates patient understanding of the proposed procedure.


Subject(s)
Plastic Surgery Procedures , Rectal Neoplasms/surgery , Female , Humans , Male , Pelvic Floor/surgery , Perineum/surgery , Postoperative Complications/physiopathology , Postoperative Complications/prevention & control , Surgical Flaps , Vagina/surgery
9.
J Am Acad Dermatol ; 37(1): 85-92, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9216528

ABSTRACT

BACKGROUND: Topical therapy providing initial improvement and maintenance of effect after treatment of the large majority of patients with limited, mild to moderate psoriasis is not presently available. Previous topical retinoids have generally been either ineffective or too irritating for therapy of psoriasis. OBJECTIVE: Our purpose was to evaluate a new topical retinoid, tazarotene, in the treatment of stable plaque psoriasis during treatment and posttreatment periods. METHODS: In a double-blind manner, 324 patients were randomly selected to receive tazarotene 0.1% or 0.05% gel, or vehicle control, once daily for 12 weeks and were then followed up for 12 weeks after treatment. RESULTS: Of the total, 318 patients could be evaluated. Tazarotene gels were superior (p < 0.05) to vehicle, often as early as treatment week 1, in all efficacy measures: plaque elevation, scaling, and erythema; treatment response; percentage treatment success (patients with > or = 50% improvement); and time to initial success. Efficacy was equivalent on target lesion sites (trunk or limbs and knees or elbows) and overall. A sustained therapeutic effect was observed for 12 weeks after treatment. Tazarotene gel was cosmetically acceptable. There was low systemic absorption, limiting toxicity to local irritation. CONCLUSION: Once-daily tazarotene was effective and safe as a topical monotherapy for plaque psoriasis, providing rapid reduction of signs and symptoms.


Subject(s)
Nicotinic Acids/administration & dosage , Psoriasis/drug therapy , Administration, Topical , Adolescent , Adult , Aged , Aged, 80 and over , Double-Blind Method , Female , Gels , Humans , Male , Middle Aged , Nicotinic Acids/adverse effects , Nicotinic Acids/pharmacokinetics , Pharmaceutical Vehicles/administration & dosage , Psoriasis/pathology
10.
Cancer ; 79(5): 1049-54, 1997 Mar 01.
Article in English | MEDLINE | ID: mdl-9041170

ABSTRACT

BACKGROUND: Secondary acute myeloid leukemia (AML) after treatment with epipodophyllotoxins is being observed with increased frequency. Therapeutic options are limited for patients with secondary AML and the role of bone marrow transplantation is unclear. METHODS: The authors report the treatment outcome of a cohort of 17 children who developed epipodophyllotoxin-induced secondary AML after therapy for childhood acute lymphoblastic leukemia (ALL) that included etoposide but no irradiation or alkylating agents. Thirteen patients (76%) had 11q23 chromosomal abnormalities that were not present at the initial diagnosis of ALL. RESULTS: Remission induction was attempted in 16 children, with 13 (81%) achieving a complete remission. After consolidation, 9 of these 13 patients received a bone marrow transplant (BMT): 2 with 4-hydroperoxycyclophosphamide-purged autologous marrow, 4 from a human leukocyte antigen (HLA)-identical sibling, 1 from a mismatched parental donor, and 2 from a matched unrelated donor. One additional child underwent allogeneic BMT without an attempt at reinduction. Of the 10 patients who received transplants, 2 were alive and well 27+ and 36+ months, respectively, after BMT. Of the 7 patients who did not receive a transplant, at last follow-up 1 had survived off therapy for 8 months for recurrent ALL whereas 6 died of AML. CONCLUSIONS: These data confirm the poor prognosis of secondary AML after epipodophyllotoxin treatment for childhood ALL. Although patients with secondary AML can achieve a remission, it is usually of brief duration. Allogeneic BMT may offer the possibility of long term remission in some of these patients. More information is needed to better define the risks and benefits of epipodophyllotoxin therapy for childhood ALL.


Subject(s)
Burkitt Lymphoma , Leukemia, Myeloid/chemically induced , Neoplasms, Second Primary/chemically induced , Podophyllotoxin/adverse effects , Acute Disease , Bone Marrow Transplantation , Child , Child, Preschool , Female , Humans , Infant , Leukemia, Myeloid/therapy , Male , Neoplasms, Second Primary/therapy , Survival Analysis
11.
Antimicrob Agents Chemother ; 39(7): 1546-53, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7492102

ABSTRACT

Acyclovir treatment of acute herpes zoster speeds rash healing and decreases pain and ocular complications. The limited oral bioavailability of acyclovir necessitates frequent dosing. Valaciclovir, the l-valyl ester of acyclovir, is rapidly and almost completely converted to acyclovir in vivo and gives three- to fivefold increases in acyclovir bioavailability. In a randomized, double-blind, multicenter study, the safety and efficacy of oral valaciclovir given at a dosage of 1,000 mg three times daily for 7 or 14 days and oral acyclovir given at a dosage of 800 mg five times daily for 7 days were compared in immunocompetent adults aged > or = 50 years with herpes zoster. Patients were evaluated for 6 months. The intent-to-treat analysis (1,141 patients) showed that valaciclovir for 7 or 14 days significantly accelerated the resolution of herpes zoster-associated pain (P = 0.001 and P = 0.03, respectively) compared with acyclovir; median pain durations were 38 and 44 days, respectively, versus 51 days for acyclovir. Treatment with valaciclovir also significantly reduced the duration of postherpetic neuralgia and decreased the proportion of patients with pain persisting for 6 months (19.3 versus 25.7%). However, there were no differences between treatments in pain intensity or quality-of-life measures. Cutaneous manifestations resolved at similar rates in all groups. Adverse events were similar in nature and prevalence among groups, and no clinically important changes occurred in hematology or clinical chemistry parameters. Thus, in the management of immunocompetent patients > or = 50 years of age with localized herpes zoster, valaciclovir given at 1,000 mg three times daily for 7 days accelerates the resolution of pain and offers simpler dosing, while it maintains the favorable safety profile of acyclovir.


Subject(s)
Acyclovir/analogs & derivatives , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Herpes Zoster/drug therapy , Herpes Zoster/immunology , Valine/analogs & derivatives , Acyclovir/adverse effects , Acyclovir/pharmacokinetics , Administration, Oral , Aged , Aged, 80 and over , Analgesics/therapeutic use , Antiviral Agents/adverse effects , Antiviral Agents/pharmacokinetics , Double-Blind Method , Drug Administration Schedule , Female , Herpes Zoster/complications , Herpes Zoster Ophthalmicus/complications , Herpes Zoster Ophthalmicus/drug therapy , Herpes Zoster Ophthalmicus/immunology , Humans , Immunocompetence , Male , Middle Aged , Neuralgia/drug therapy , Neuralgia/etiology , Pain/drug therapy , Pain/etiology , Quality of Life , Valacyclovir , Valine/adverse effects , Valine/therapeutic use
12.
Proc Natl Acad Sci U S A ; 92(12): 5461-4, 1995 Jun 06.
Article in English | MEDLINE | ID: mdl-7777531

ABSTRACT

Infection by human immunodeficiency virus type 1 (HIV-1) causes acquired immunodeficiency syndrome (AIDS) after a long clinical latency. This disease is associated with a spectrum of cancers. Here we report that wild-type p53 is a potent suppressor of Tat, a major transactivator of HIV-1. Reciprocally, Tat inhibits the transcription of p53. Downregulation of p53 by upregulated tat may be important for the establishment of productive viral infection in a cell and also may be involved in the development of AIDS-related malignancies.


Subject(s)
Gene Products, tat/physiology , HIV-1/genetics , Tumor Suppressor Protein p53/physiology , Base Sequence , DNA, Complementary , Down-Regulation , Gene Products, tat/genetics , Genes, p53 , Genes, tat , HIV Long Terminal Repeat , Humans , Molecular Sequence Data , Promoter Regions, Genetic , Transcriptional Activation , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/physiology , Tumor Suppressor Protein p53/genetics , tat Gene Products, Human Immunodeficiency Virus
13.
Public Health Rep ; 110(3): 246-50, 1995.
Article in English | MEDLINE | ID: mdl-7610211

ABSTRACT

Massachusetts has developed the first State profile of the causes and costs of injury based on the national study, "Cost of Injury in the United States: A Report to Congress." Incidence of fatal injuries is based on Massachusetts data; nonfatal hospitalized injuries, on Massachusetts age and sex rates and U.S. cause data; and nonhospitalized injuries, on U.S. rates applied to Massachusetts census data. Lifetime costs per injured person are based on national data adjusted for higher personal health care expenditures and for higher mean annual earnings in Massachusetts. The estimated total lifetime cost for the 1.4 million injuries that occurred in 1989 is $4.4 billion--$1.7 billion for health care and $2.7 billion for lost earnings. Injuries attributed to motor vehicles and falls account for more than half of the total cost. The other cause categories are poisonings, fire-burns, firearms, drowings-near drownings, and other. For every person who dies from an injury, 17 people are hospitalized, and an estimated 535 people require outpatient treatment, consultation, or restricted activity. Development of a State-based cost report can be useful in monitoring the contribution of injuries to health status and in planning effective injury prevention strategies in a community-based health care system. The methodology described in this paper can be replicated by other States through accessing their State-specific mortality and hospital discharge data bases.


Subject(s)
Wounds and Injuries/economics , Wounds and Injuries/epidemiology , Accidents, Traffic/mortality , Accidents, Traffic/statistics & numerical data , Adult , Aged , Costs and Cost Analysis , Female , Health Care Costs , Hospitalization/statistics & numerical data , Humans , Incidence , Male , Massachusetts/epidemiology , Value of Life , Wounds and Injuries/etiology
14.
Science ; 268(5209): 429-31, 1995 Apr 21.
Article in English | MEDLINE | ID: mdl-7716549

ABSTRACT

Infection by human immunodeficiency virus-type 1 (HIV-1) is typified by the progressive depletion of CD4 T lymphocytes and deterioration of immune function in most patients. A central unresolved issue in acquired immunodeficiency syndrome (AIDS) pathogenesis is the mechanism underlying this T cell depletion. HIV-1 Tat protein was shown to induce cell death by apoptosis in a T cell line and in cultured peripheral blood mononuclear cells from uninfected donors. This Tat-induced apoptosis was inhibitable by growth factors and was associated with enhanced activation of cyclin-dependent kinases.


Subject(s)
Apoptosis , CDC2-CDC28 Kinases , Gene Products, tat/physiology , HIV-1 , Leukocytes, Mononuclear/cytology , T-Lymphocytes/cytology , Base Sequence , Cyclin-Dependent Kinase 2 , Cyclin-Dependent Kinases/metabolism , Enzyme Activation , Gene Products, tat/pharmacology , Genes, tat , Humans , Leukocytes, Mononuclear/enzymology , Molecular Sequence Data , Protein Serine-Threonine Kinases/metabolism , Recombinant Proteins/pharmacology , T-Lymphocytes/enzymology , Transfection , Tumor Cells, Cultured , tat Gene Products, Human Immunodeficiency Virus
15.
J Auton Pharmacol ; 15(1): 27-35, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7744888

ABSTRACT

1. Potential interaction between release-inhibiting prejunctional alpha 2-adrenoceptors and D2 dopamine receptors was investigated by measuring D2 receptor-mediated inhibition of stimulation-evoked tritium overflow from perfused rat tail arteries incubated with [3H]-noradrenaline. 2. In the presence of cocaine (10(-5)M), which enhanced stimulation-evoked tritium overflow, the D2 dopamine agonist N-0923 [(S)-(-) 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin] (10(-8)M) was less effective at inhibiting stimulation-evoked tritium overflow compared to inhibition in the absence of cocaine. 3. In the presence of cocaine, yohimbine (10(-6)M) enhanced stimulation-evoked [3H]-noradrenaline release. Under these conditions, inhibition produced by N-0923 was enhanced compared to tissues without yohimbine. 4. In the presence of cocaine, the alpha 2-adrenoceptor agonist UK-14,304 (10(-7)M) reduced stimulation-evoked tritium overflow. However, in this case, N-0923-mediated inhibition was not significantly altered. 5. In most circumstances increasing or reducing activation of prejunctional alpha 2-adrenoceptors resulted in attenuation or enhancement, respectively, of D2 receptor activation. However, in the case of UK-14,304 this relationship did not hold. Thus, most but not all the evidence supports an interaction between prejunctional alpha 2-adrenoceptors and D2 dopamine receptors.


Subject(s)
Receptors, Adrenergic, alpha/physiology , Receptors, Dopamine D2/physiology , Sympathetic Nervous System/physiology , Adrenergic alpha-Agonists/pharmacology , Animals , Brimonidine Tartrate , Cocaine/pharmacology , Electric Stimulation , In Vitro Techniques , Male , Quinoxalines/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Adrenergic, alpha/drug effects , Receptors, Dopamine D2/agonists , Receptors, Dopamine D2/drug effects , Sympathetic Nervous System/drug effects , Tail/blood supply , Tetrahydronaphthalenes/pharmacology , Thiophenes/pharmacology , Yohimbine/pharmacology
16.
Blood ; 84(6): 2050-4, 1994 Sep 15.
Article in English | MEDLINE | ID: mdl-8081006

ABSTRACT

Eighteen patients with Fanconi anemia (FA) with evidence of bone marrow (BM) aplasia underwent allogenic BM transplants (BMT) from matched sibling donors (MSD). Median age at BMT was 7.6 years. Conditioning consisted of low-dose cyclophosphamide (CY; 5 mg/kg x 4 days) and thoracoabdominal irradiation (TAI; 400 cGy). Graft-versus-host disease (GVHD) prophylaxis included cyclosporin A and prednisone. In addition antithymocyte globulin (ATG) was administered in the pretransplant period to promote engraftment and in the posttransplant period for additional GVHD prophylaxis. Engraftment occurred rapidly (median, 12 days for an absolute neutrophil count > or = 0.5 x 10(9)/L; median, 22 days for platelet count > or = 50 x 10(9)/L). Seventeen patients have sustained engraftment and are transfusion-independent, with Lansky scores of 100% at median follow-up of 27 months. One patient developed graft failure 4 months after initial engraftment and required a second BM infusion. None of the patients developed acute GVHD; 3 patients (16%) developed chronic GVHD. BMT is a feasible option for FA patients having an MSD and should be performed at a young age and early in the course of the disease, before the development of complications. We believe the addition of ATG to the transplant regimen of low-dose CY, TAI, and cyclosporin was responsible for improvement in the survival of FA patients undergoing BMT. The regimen was well tolerated and was associated with a low incidence of complications including GVHD.


Subject(s)
Bone Marrow Transplantation , Fanconi Anemia/therapy , Abdomen/radiation effects , Child , Child, Preschool , Chronic Disease , Cyclophosphamide/therapeutic use , Cyclosporine/therapeutic use , Family , Fanconi Anemia/immunology , Female , Graft vs Host Disease/prevention & control , Histocompatibility , Humans , Infant , Male , Prednisone/therapeutic use , Thorax/radiation effects , Tissue Donors
17.
Life Sci ; 54(21): 1545-57, 1994.
Article in English | MEDLINE | ID: mdl-7910929

ABSTRACT

Influx of calcium through voltage-dependent N-type calcium channels promotes the release of norepinephrine from nerve terminals. Contributions by L- and N-type calcium channels at different levels of nerve stimulation were examined in perfused rat tail arteries loaded with [3H]norepinephrine. Nifedipine had no effect while omega-conotoxin reduced tritium efflux by 69 to 82% depending on the stimulation intensity. Thus, N-type calcium channels predominated in the control of norepinephrine release, and the relative contribution of L- and N-type channels did not change when stimulation intensity was altered. We also explored the effect of calcium channel blockers on modulation of norepinephrine release by D2 dopamine receptors. Inhibition of stimulation-evoked tritium efflux by the D2 agonist N-0923 was similar in the absence and presence of nifedipine and/or omega-conotoxin. We conclude that D2 dopamine receptors are not coupled to L-type calcium channels; however, the role of N-type calcium channels requires further investigation.


Subject(s)
Arteries/innervation , Calcium Channel Blockers/pharmacology , Norepinephrine/metabolism , Receptors, Dopamine D2/physiology , omega-Conotoxins , Animals , Calcium Channels/drug effects , Calcium Channels/physiology , Dopamine Agents/pharmacology , Electric Stimulation , Male , Nifedipine/pharmacology , Peptides/pharmacology , Rats , Rats, Sprague-Dawley , Receptors, Dopamine D2/drug effects , Tetrahydronaphthalenes/pharmacology , Thiophenes/pharmacology
18.
Eur J Pharmacol ; 252(1): 1-9, 1994 Jan 24.
Article in English | MEDLINE | ID: mdl-7908641

ABSTRACT

Possible age-related changes in the roles of L- and N-type Ca2+ channels and dopamine D2 receptors in control of norepinephrine release were investigated in tail arteries of F-344 rats. Nifedipine had no effect on stimulation-evoked tritium efflux at 6 or 24 months of age; however, omega-conotoxin GVIA reduced efflux by 70 to 80% at both ages even when frequency of stimulation was altered. Activation of prejunctional dopamine D2 receptors by the selective agonist N-0923 [(S)-(-)-2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin++ +] inhibited contractile responses to transmural nerve stimulation in a frequency and concentration-dependent manner. Effects were similar from 6 to 26 months. Furthermore inhibition by N-0923 of stimulation-evoked [3H]norepinephrine efflux was not different at 12 and 24 months. Thus, N-type Ca2+ channels predominate in control of norepinephrine release, and this is unchanged with advancing age or stimulation intensity. Furthermore, D2 receptor-mediated inhibition of norepinephrine release is not altered with advancing age.


Subject(s)
Aging/metabolism , Calcium Channels/metabolism , Muscle, Smooth, Vascular/drug effects , Norepinephrine/metabolism , Receptors, Dopamine D2/metabolism , Sympathetic Nervous System/metabolism , Animals , Arteries/innervation , Calcium Channel Blockers/pharmacology , Dopamine Agents/pharmacology , In Vitro Techniques , Male , Muscle Contraction , Muscle, Smooth, Vascular/innervation , Nifedipine/pharmacology , Peptides/pharmacology , Rats , Rats, Inbred F344 , Sympathetic Nervous System/drug effects , Tail/blood supply , Tetrahydronaphthalenes/pharmacology , Thiophenes/pharmacology , omega-Conotoxin GVIA
19.
Public Health Rep ; 108(3): 363-71, 1993.
Article in English | MEDLINE | ID: mdl-8497575

ABSTRACT

National data reveal that low birth weight and infant mortality rates among Hispanics are, in general, between the rates for whites and those for blacks. The question remains, do differences in low birth weight reflect distributions of known risk factors, or do ethnic differences persist after simultaneously adjusting for intervening variables? In this study, Massachusetts birth certificate data for 206,973 white non-Hispanic infants and 19,571 Hispanic infants are used to examine differences in low birth weight between white non-Hispanic and Hispanic infants, as well as variation among seven subgroups of Hispanic mothers--Puerto Rican, Dominican, Central American, South American, Mexican, Cuban, and other Hispanic. Regression analysis is used to estimate the association between risk factors and birth weight and the relative risk of low birth weight. Risk factors include ethnicity, demographic characteristics, biological factors, access to prenatal care, and infants' conditions. Results indicate substantial variation in mean birth weight, low birth weight, and levels of risk among Hispanic subgroups and between Hispanics and white non-Hispanics. Puerto Rican infants had the lowest mean birth weight and, in general, the highest level of risk factors in this population. None of the adjusted odds ratios for low birth weight for any Hispanic group was significantly elevated at the 95 percent level compared with white non-Hispanics. Findings in this study confirm the previous observations of the wide variation among Hispanic subgroups and the high level of risk among Puerto Ricans. Results of this study also raise some interesting questions about the differential relationship between ethnicity and birth weight, ethnicity and low birth weight, and the significance of maternal place of birth as a proxy measure of adaptation or acculturation.


Subject(s)
Infant Mortality , Infant, Low Birth Weight , Pregnancy Complications , Adult , Age Factors , Cohort Studies , Demography , Educational Status , Female , Gestational Age , Health Services Accessibility , Hispanic or Latino , Humans , Infant, Newborn , Massachusetts/epidemiology , Middle Aged , Parity , Pregnancy , Prenatal Care/statistics & numerical data , Risk Factors , Sex Factors , Smoking
20.
Ethn Dis ; 3(3): 255-69, 1993.
Article in English | MEDLINE | ID: mdl-8167542

ABSTRACT

This paper examines the association of ethnicity and birthweight, adjusted for other maternal and infant characteristics, among black women who gave birth in Massachusetts from 1987 through 1989. Data are drawn from the standard certificate of live birth, which includes questions on race and ethnicity/ancestry as well as birthweight; maternal sociodemographic and biological characteristics; access to prenatal care; and infant characteristics. The study cohort consists of 18,571 black infants and a comparison group of 206,358 non-Hispanic white infants. Infants whose mothers reported their race as black were further categorized into six ethnic groups: American, Haitian, West Indian, Cape Verdean, Hispanic, and other black. In addition to descriptive analyses, we used multiple linear regression to measure the association between ethnicity, other characteristics, and birthweight; and we used multiple logistic regression to measure the odds ratio of low birthweight (ranging from 500 g to 2499 g) for the six black ethnic groups, adjusted for other characteristics. Results indicate that Americans have lower mean birthweight and generally higher levels of risk than other black ethnic groups. Compared to the reference group of non-Hispanic whites, Americans (OR = 1.49), other blacks (OR = 1.41), and West Indians (OR = 1.37) have significantly elevated relative risks of low birthweight.


Subject(s)
Birth Weight , Black or African American , Ethnicity , Mothers , Adult , Africa/ethnology , Black People , Female , Haiti/ethnology , Hispanic or Latino , Humans , Infant, Low Birth Weight , Infant, Newborn , Massachusetts , Pregnancy , Risk Factors , West Indies/ethnology
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