ABSTRACT
We use an ultrafast optical pump-probe spectroscopy to study quasiparticle (QP) dynamics in a topological insulator LaBi. Temperature-dependent optical measurements have been carried out, by which we observed nearly constant fast component (with a lifetime of 0.15 ps) and slow component (with a lifetime of 1.5 ps) for the whole range from 10â K to 295â K. The laser fluence dependence result shows that there is no saturation for the QP dynamics up to 3.3 mJ /cm2. Moreover, an Eg mode transverse optical (TO) coherent phonon has also been observed, with a frequency of 2.8 THz. Our results provide for the first time the ultrafast dynamics information of both the QPs and coherent phonons in a nodal line topological material.
ABSTRACT
Objective: To investigate the clinicopathologic features and differential diagnosis of breast lymphoma in core needle biopsy. Methods: Seventy-two cases of breast lymphoma in core needle biopsy between 2011 and 2016 were extracted from the pathology database of Fudan University Shanghai Cancer Center. The clinicopathologic features were analyzed. The histological diagnosis of the tumors was based on the WHO classifications of tumors of hematopoietic and lymphoid tissues. Immunohistochemistry and molecular methods were performed to detect related antigens and genes. Results: Seventy-one patients were female and one was male. The median age was 54 years. The tumors were located in the right breast in 32 (44.4%) patients and in the left breast in 40 (55.6%) patients. Seven patients had a previous history of lymphoma. Most of the cases presented as a single and painless breast mass. Sixty-three patients received systemic treatment, and nine patients received systemic therapy after excision. The common morphological feature was that single tumor cells infiltrated the stroma, without cohesiveness between tumor cells, and lacking glandular or nested epithelioid structures. The normal ductal and lobular structures of the mammary gland were typically preserved. The tumor cells in some cases were distributed in single rows, and should be differentiated from invasive carcinoma. All cases were positive for LCA, negative for CK. Sixty-eight cases were classified as B-cell lymphoma, including 63 cases (87.5%) of diffuse large B-cell lymphoma (DLBCL; including 3 cases of EBV-positive DLBCL and 60 cases of DLBCL, NOS), two cases of Burkitt lymphoma, one case of mantle cell lymphoma, one case of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and one case of precursor B lymphoblastic leukemia/lymphoma. The remaining cases included two peripheral T-cell lymphoma (NOS), one extranodal NK/T cell lymphoma, nasal type and one myeloid sarcoma. In 63 cases of DLBCL, 22 cases (34.9%) expressed germinal center B-cell-like (GCB) phenotype and 41 cases (65.1%) showed non-germinal center B-cell-like (non-GCB) phenotype. Conclusions: Core needle biopsy could be the preferred method for diagnosis of breast lymphoma. Diffuse large B-cell lymphoma is the most common histologic type of breast lymphoma, and non-GCB subtype is more frequent than GCB subtype.
Subject(s)
Breast Neoplasms , Lymphoma , B-Lymphocytes , Biopsy, Large-Core Needle , China , Diagnosis, Differential , Female , Germinal Center , Humans , Immunohistochemistry , Lymphoid Tissue , Male , Middle AgedABSTRACT
Objective: To study the clinicopathologic characteristics and differential diagnosis of mammary myofibroblastoma. Methods: Nine cases of mammary myofibroblastoma diagnosed between 2006 and 2017 were collected from the Department of Pathology, Fudan University Shanghai Cancer Center. Clinical and histopathologic features of these nine cases were examined, immunohistochemical staining was performed, FISH analysis for the detection of FOXO1 gene was performed in one case, and follow-up data were also collected. Results: There were seven female and two male patients, with a mean age of 54 years, median age of 50 years (ranging from 40 to 83 years). Four lesions each were located in the left and right breast, and one was in the left subaxillary accessory breast tissue. Clinically, 8 patients presented with a breast mass, 3 of which accompanied with pain. All of the tumors were well-demarcated grossly with a mean diameter of 2.5 cm. Microscopically, there were no entrapped ductal or lobular structures within the tumor. Seven tumors were classic type, which were composed of bland-looking spindle neoplastic cells without mitoses, arranging in intersecting fascicles, and interrupted by thick hyalinized collagen bundles. One case was of epithelioid variant, demonstrating epithelioid neoplastic cells diffusely arranged or in cluster. The other one case was mixed spindle and epithelioid-cell type. Atypical tumor cells were observed in 3 cases. Immunohistochemically, tumor cells were diffusely positive for desmin (9/9) and CD34 (6/9), as well as ER (7/7), PR (6/6) and bcl-2 (3/3). SMA (4/7) and Calponin (1/2) were focally or partially positive in some cases. H-caldesmon (1/2) was weakly positive and epithelial markers were negative. Ki-67 proliferation index was low (<10%). There was no monoallelic loss of FOXO1/13q14 loci in the detected case according to FISH analysis. Follow-up data were available for all patients, and follow-up period ranged from 12 to 78 months. All patients remained well without recurrence. Conclusions: Mammary myofibroblastoma is a rare benign mesenchymal tumor. In some circumstances, it may exhibit confusing morphologies, including some variants. The epithelioid variant of mammary myofibroblastoma might mimic invasive lobular carcinoma, leading to the diagnostic dilemmas and even misdiagnosis, especially in core needle biopsy specimen or frozen sections. Familiarity with the characteristics of this tumor is of great importance for accurate diagnosis and proper treatment.
Subject(s)
Breast Neoplasms , Neoplasms, Muscle Tissue , Adult , Biomarkers, Tumor , Breast , Calcium-Binding Proteins , Calmodulin-Binding Proteins , Carcinoma, Lobular , China , Collagen , Desmin , Diagnosis, Differential , Diagnostic Errors , Epithelioid Cells , Female , Humans , Immunohistochemistry , Male , Microfilament Proteins , Middle Aged , Mitotic Index , Neoplasm Recurrence, Local , CalponinsABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Histone deacetylase 6 (HDAC6) is frequently altered in DLBCL and inhibition of HDAC6 has potent anti-tumor effects in vitro and in vivo. We profiled miRNAs that altered in the HDAC6 knockdown DLBCL cells with NanoString nCounter assay and identified microRNA-27b (miR-27b) as the most significantly increased miRNA. We validated decreased expression of miR-27b in DLBCL tissues, and we found that low expression of miR-27b was associated with poor overall survival of patients with DLBCL. In addition, forced expression of miR-27b suppressed DLBCL cell viability and proliferation in vitro, and inhibited tumor growth in vivo. Mechanistically, Rel A/p65 is found to negatively regulate miR-27b expression, and its acetylation and block of nuclear translocalization caused by HDAC6 inhibition significantly elevates miR-27b expression. Furthermore, miR-27b targets MET and thus represses the MET/PI3K/AKT pathway. These findings highlight an important role of miR-27b in the development of DLBCL and uncover a HDAC6-Rel A/p65-miR-27b-MET signaling pathway. Elevating miR-27b through HDAC6 inhibition would be a promising strategy for DLBCL treatment.
Subject(s)
Apoptosis/genetics , Gene Expression Regulation, Neoplastic , Histone Deacetylase 6/metabolism , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/metabolism , MicroRNAs/genetics , Proto-Oncogene Proteins c-met/genetics , Biomarkers , Cell Line, Tumor , Cell Proliferation , Gene Expression Profiling , Humans , Lymphoma, Large B-Cell, Diffuse/mortality , Lymphoma, Large B-Cell, Diffuse/pathology , Prognosis , RNA Interference , Signal Transduction , Transcription Factor RelA/metabolismABSTRACT
Objective: To evaluate the morphological and immunohistochemical features of infiltrating epitheliosis and its differential diagnosis. Methods: Nine consultation and routine cases of infiltrating epitheliosis diagnosed from January 2015 to December 2016 in Fudan University Shanghai Cancer Center were collected. All tissues were formalin-fixed paraffin-embedded and routinely HE stained. The HE slides were reviewed. Immunohistochemical staining of CKpan, CK7, CK19, CK5/6, CK14, p63, SMMHC, Calponin, ER, PR, HER2, Ki-67 and S-100 protein was performed using Ventana BenchMark automated immunostainer. Results: The morphological features of infiltrating epitheliosis included: (1) Florid proliferation of epithelial cells forming solid nests or papillary, glandular and cord-like pattern. The proliferative cells possessed nuclei of varying size and shape without atypia. (2) The stroma was altered, showing varying degrees of fibrosis or sclerosis. (3) The proliferative epithelial nests might flow into the spaces within small ducts and lobules at the periphery of the lesion, resulting in pseudo-infiltration. Immunohistochemically, infiltrating epitheliosis was non-uniformly positive for ER/PR, and was positive for high molecular weight CK5/6 and CK14. Myoepithelial markers p63, SMMHC and Calponin demonstrated intact, partial or entire loss of myoepithelial cells around the epithelial nests. The loss of myoepithelial markers staining was more frequent at the periphery of the lesion. The most important differential diagnoses included invasive ductal carcinoma, ductal carcinoma in situ (DCIS), and low grade adenosquamous carcinoma, etc. Conclusions: Infiltrating epitheliosis is an important pseudo-infiltrating lesion. The lack of atypia, non-uniform ER/PR expression, positivity for high molecular weight cytokeratins, and the intact to partial to entire loss of myoepithelial markers around the proliferating cell nests are the key points to differentiate it from invasive carcinomas and DCIS.
Subject(s)
Breast/pathology , Epithelial Cells/pathology , Biomarkers/metabolism , Breast/metabolism , Breast/ultrastructure , Breast Neoplasms/pathology , Carcinoma, Adenosquamous/pathology , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , China , Diagnosis, Differential , Epithelial Cells/metabolism , Epithelial Cells/ultrastructure , Female , Humans , Immunohistochemistry , Neoplasm Proteins/metabolismABSTRACT
Objective: To investigate androgen receptor(AR)expression in invasive breast carcinoma and the correlation with surrogate molecular breast carcinoma subtypes. Methods: Immunohistochemical staining of AR and other biomarkers was performed in a cohort of 870 cases of primary invasive breast carcinomas collected from August to December, 2016. The association of AR expression with different histological and surrogate molecular subtypes was analyzed. Results: The positive expression rate of AR in the immunohistochemistry-based surrogate subtypes was 96.3%(207/215) for Luminal A, 89.8%(378/421) for Luminal B, 82.4%(75/91) for HER2 overexpression and 37.1%(53/143) for triple negative breast carcinoma, with significant differences among the four groups (P<0.01). AR correlated positively with the expression of ER(P<0.01), PR(P<0.01), HER2(P=0.007), GATA3(P<0.01), GCDFP15(P<0.01)and mammaglobin(P<0.01), while negatively with the expression of Ki-67(P<0.01), CK5/6(P<0.01)and CK14(P<0.01). Conclusions: AR exhibits a high expression in invasive breast carcinoma, which is mainly correlated with ER-positive breast carcinoma. Regardless of the relatively low expression rate, AR is a potential therapeutic target in triple negative breast carcinoma.
Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/chemistry , Receptors, Androgen/analysis , Aged , Breast Neoplasms/pathology , Creatine Kinase/analysis , Female , GATA3 Transcription Factor/analysis , Humans , Immunohistochemistry , Receptor, ErbB-2/analysis , Triple Negative Breast Neoplasms/chemistryABSTRACT
OBJECTIVE: We compared the effects and complications in resection of the congenital choledochal cyst (CCC) and hepatic duct jejunum Roux-Y anastomosis by laparoscopy and open surgery. PATIENTS AND METHODS: We continuously selected 156 cases of pediatric patients with CCC, which were divided into 70 cases of the laparoscopic group and 86 cases of laparotomy group according to the treatment methods. Then the success rate of surgery, intraoperative and postoperative bleeding, intraoperative and postoperative complications was compared. RESULTS: It was found that after 65 cases (92.9%) completed in the laparoscopic group and all completed in laparotomy group there was less intra-operative blood loss of laparoscopic group than that of the open surgery group. However, the difference of postoperative hemorrhage in two groups was not statistically significant (p >0.05). The intra-operative complications in the two groups were not significantly different (p >0.05); in the laparoscopic group, the postoperative complication rate was significantly lower than open surgery group (p <0.05). CONCLUSIONS: Laparoscopic resection of CCC combined with jejunum Roux-Y anastomosis has good prospects.
Subject(s)
Choledochal Cyst/surgery , Laparoscopy , Anastomosis, Roux-en-Y , Child , Humans , Jejunum , Laparoscopes , Treatment OutcomeABSTRACT
OBJECTIVE: This exploratory study investigated the relation between psychological mood states and hemodynamic variables obtained at rest. METHODS: We measured resting hemodynamic variables using impedance cardiography, blood pressure, heart rate, and the Profile of Mood States (POMS) in 71 participants. RESULTS: Mood states were not significantly associated with heart rate, systolic, diastolic, or mean arterial pressure. In comparison with these basic measures of physiology, a number of impedance derived measures of hemodynamics were associated with mood states. Log stroke volume was negatively correlated with POMS tension-anxiety (r = -.319, p = .009) and fatigue-inertia (r = -. 316, p = .009). Log cardiac output was negatively associated with fatigue-inertia (r = -.346, p < .01). Log total peripheral vascular resistance was positively correlated with POMS fatigue-inertia (r = .276, p = .024). CONCLUSIONS: Our findings suggest that mood states are associated with hemodynamic variables underlying blood pressure.
Subject(s)
Affect/physiology , Hemodynamics , Adult , Blood Pressure , Cardiac Output , Cardiography, Impedance , Female , Heart Rate , Humans , Hypertension , Male , Middle Aged , Stroke Volume , Vascular ResistanceABSTRACT
BACKGROUND: Cockroach allergy and exposure to high levels of this allergen are important in the increasing asthma-related health problems among young inner-city children. However, there are very little data regarding the prevalence of cockroach allergy in infants and young children with asthma. OBJECTIVE: This retrospective study was designed to test the hypothesis that cockroach allergy appears early in life in young children with recurrent wheezing. METHODS: We reviewed the medical records of all 196 children (ages 5 months to 16 years) evaluated between January 1995 and September 1997 at the Cook County Hospital Pediatric Allergy Clinic for recurrent wheezing. The patients were assigned into two age groups, less than 4 years old and 4 to 16 years old. The percentages of IgE skin tests positive for common aeroallergens were compared within and between the two age groups. All children in the younger age group were tested for cockroach and dust mites, cat, and dog when indicated by positive environmental history. All children in the older age group were tested for indoor and outdoor allergens. RESULTS: Sixty-three children were younger than 4 years of age, and of these, 15 (23.8%) had cockroach allergen sensitivity, compared with only eight patients (12.7%) who were skin test positive to dust mite allergen (P = .01). The youngest patient with a positive reaction to cockroach allergen was 6 months old. Patients with a single allergen skin reactivity were considered as monosensitized. Nine children younger than 4 years of age (14.3%) were monosensitized only to cockroach allergen in contrast to three children (4.8%) who were monosensitized to house-dust mites (P < .05). CONCLUSIONS: Our data suggest that cockroach allergen sensitivity starts early in life and may be the only sensitizing allergen in many young inner-city children.
Subject(s)
Cockroaches/immunology , Hypersensitivity/epidemiology , Respiratory Sounds/physiopathology , Adolescent , Air Pollution, Indoor/analysis , Animals , Child , Child, Preschool , Humans , Infant , Prevalence , Retrospective Studies , Skin Tests , Urban HealthSubject(s)
Cardiomegaly/etiology , Immunity, Maternally-Acquired , Lupus Erythematosus, Systemic/congenital , Myocardium/pathology , RNA, Small Cytoplasmic , Adult , Antibodies, Antinuclear/blood , Autoantigens/immunology , Cardiomegaly/diagnosis , Cardiomegaly/pathology , Cardiomegaly/surgery , Complement C3/deficiency , Complement C4a/deficiency , Complement C4a/genetics , Complement C4b/genetics , Diagnosis, Differential , Female , Fetal Diseases/diagnosis , Fetal Heart/physiopathology , Heart Block/diagnosis , Heart Block/embryology , Heart Failure/etiology , Heart Failure/pathology , Heart Failure/surgery , Heart Transplantation , Humans , Immunoglobulin G/analysis , Infant , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/pathology , Male , Maternal-Fetal Exchange , Myocardium/immunology , Pregnancy , Pregnancy Complications/blood , Pregnancy Complications/immunology , Ribonucleoproteins/immunology , Virus Diseases/complications , Vomiting/etiology , SS-B AntigenABSTRACT
Sleep apnea can lead to marked psychological distress including some mood symptoms. Previous studies on continuous positive airway pressure (CPAP) treatment usually reported significant improvement in mood symptoms in patients with sleep apnea, but most of them did not consider the placebo effect of CPAP. We examined the effect of CPAP treatment on mood states by employing both CPAP treatment and placebo CPAP. Twenty five men and nine women with sleep apnea underwent two successive nights of polysomnography (PSG) during hospitalization. The Profile of Mood States (POMS) was administered to measure mood states. Patients were randomly assigned to either CPAP treatment group or placebo CPAP group. After 7 days of CPAP use at home, all patients were re-hospitalized to undergo one more night of nocturnal PSG with their assigned treatment (CPAP treatment or placebo CPAP). They also had a repeat evaluation of mood by completing the POMS. Only patients on CPAP treatment improved significantly in apnea index, respiratory disturbance index, and mean oxygen saturation. However, both CPAP treatment group and placebo CPAP group showed significant improvement in mood states. In conclusion, the effect of CPAP treatment on mood symptoms in apneic patients could be a placebo effect. CPAP treatment may be effective in improving mood states only in patients who have severe depressive symptoms secondary to sleep apnea.
Subject(s)
Affect , Positive-Pressure Respiration , Sleep Apnea Syndromes/therapy , Adult , Depression/psychology , Depression/therapy , Female , Humans , Male , Middle Aged , Personality Inventory , Polysomnography , Sleep Apnea Syndromes/psychology , Treatment OutcomeABSTRACT
This article reviews the literature about the extent of posttraumatic stress disorder (PTSD) in patients with burns. PTSD is a relatively new diagnostic label, although the emotional effects of severe trauma have long been recognized. A burn injury-one of the most traumatic of all injuries--can be accompanied by serious psychological sequelae, including PTSD. Psychiatric symptoms may not be immediately apparent in patients with burns because the patients often develop PTSD many months after the injury. The reported prevalence rate of PTSD in patients with burns varies from 8% to 45%. The factors increasing these patients' risks include preburn affective disorder, delirium or severe pain during acute treatment, and less perceived social support. Psychosocial issues must be considered in the recovery or rehabilitation phase. Pharmacotherapy, psychodynamic psychotherapy, cognitive-behavioral therapy, and eye-movement desensitization and reprocessing may be helpful to the PTSD patient. Early detection and treatment of PTSD cannot only diminish the effects of this disabling disorder but can also help the rehabilitation of patients with this condition.
Subject(s)
Burns/psychology , Stress Disorders, Post-Traumatic/etiology , Adult , Child, Preschool , Female , Humans , Male , Prevalence , Risk Factors , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/therapyABSTRACT
There is a complex interplay between psychological states and biochemical factors. beta-Adrenergic receptor responsiveness is altered in some patients with depression and anxiety disorders, but the relation between various psychological states and receptor function in a normal population is unknown. We measured lymphocyte beta-adrenergic receptor density (Bmax), sensitivity (cAMP ratio), the Profile of Mood States (POMS), and Spielberger State-Trait Anxiety Inventory (STAI) in 39 hypertensives and 81 normotensives. We examined correlations between log normalized receptor variables and psychological states. Log Bmax showed negative correlations with age and with POMS tension-anxiety, depression-dejection, and anger-hostility. Log cAMP ratio did not show significant correlations with POMS and STAI ratings. In step-wise multiple regression analyses, 36% of the variance in Bmax was accounted for by POMS tension-anxiety, and age. Our study suggests that increased POMS tension-anxiety was highly associated with down-regulation of beta-adrenergic receptors, even in subjects who do not have psychiatric illness. Numerous psychological states could be associated with changes of beta-adrenergic receptor responsiveness in a normal population.
Subject(s)
Affect/physiology , Anger/physiology , Anxiety/metabolism , B-Lymphocytes/drug effects , Depression/metabolism , Receptors, Adrenergic, beta/drug effects , Adrenergic beta-Agonists/pharmacology , Adult , Cyclic AMP/metabolism , Female , Humans , Hypertension/metabolism , Hypertension/psychology , Isoproterenol/pharmacology , Kinetics , Male , Middle Aged , Neuropsychological TestsABSTRACT
An increased sympathetic nervous response to hypoxia and reduced beta-adrenergic receptor function have been reported in hypertension. This study examines the relationship between hypoxia and beta-adrenergic receptor function in sixteen normotensive and eight hypertensive subjects. We measured the average arterial oxygen saturation and the end tidal carbon dioxide partial pressure in hypertensive and normotensive groups under normoxia and mild isocapnic hypoxia (15% O2, 85% N2). The ratio of isoproterenol-stimulated cAMP to basal cAMP on lymphocytes was measured in the two groups under normoxia. We also measured plasma norepinephrine levels and calculated the "Chronotropic 25 Dose" of isoproterenol in the two groups under normoxia and hypoxia. Hypertensives had higher plasma norepinephrine levels for either breathing condition (F=7.16, p=0.015). Under hypoxia, hypertensives showed a significant decrease in the average arterial oxygen saturation (F=4.92, p=0.038) and higher "Chronotropic 25 Dose" implying decreased beta-adrenergic receptor sensitivity (F=6.30, p=0.011). These results suggest that hypertensives have a diminished ventilatory response and impaired beta-adrenergic response under hypoxia.
Subject(s)
Hypertension/physiopathology , Hypoxia/physiopathology , Respiratory System/physiopathology , Sympathetic Nervous System/physiopathology , Adrenergic beta-Agonists/administration & dosage , Adult , Cyclic AMP/metabolism , Female , Humans , Hypertension/complications , Hypoxia/complications , Isoproterenol/administration & dosage , Lymphocytes/drug effects , Lymphocytes/metabolism , Male , Middle Aged , Norepinephrine/blood , Receptors, Adrenergic, beta/physiology , Respiratory System/drug effects , Sympathetic Nervous System/drug effectsABSTRACT
BACKGROUND: A number of factors have previously been shown to be predictive of survival from out-of-hospital ventricular fibrillation. These include witnessed collapse, prompt initiation of cardiopulmonary resuscitation, early application of defibrillation, and younger age. Arrests occurring away from home are also associated with improved survival. Additionally, hospital mortality after successful resuscitation has been related to a history of congestive heart failure as well as to some of the factors noted above. An association of prearrest comorbidity with outcome has not been systematically evaluated. METHODS AND RESULTS: We define here a comorbidity index, which is constructed from histories of chronic conditions as well as a number of recent symptoms in 282 victims of out-of-hospital VF. This indicator of comorbidity is strongly associated with outcome (P = .004). However, when analyzing a comprehensive set of predictors of survival after out-of-hospital ventricular fibrillation, including the index of comorbidity, we could identify overall only about one fourth of the variation that one might hope to account for. CONCLUSIONS: Comorbidity appears to be an important (but usually overlooked) predictor of survival from out-of-hospital ventricular fibrillation. However, most of the statistical variability in predicting survival remains unexplained when we consider comorbidity in conjunction with previously identified predictors of survival.
Subject(s)
Comorbidity , Emergencies/epidemiology , Heart Arrest/epidemiology , Ventricular Fibrillation/epidemiology , Aged , Aged, 80 and over , Cardiopulmonary Resuscitation , Cardiovascular Diseases/epidemiology , Chronic Disease/epidemiology , Diabetes Mellitus/epidemiology , Electric Countershock , Female , Gastrointestinal Diseases/epidemiology , Heart Arrest/mortality , Heart Arrest/therapy , Hotlines , Humans , Interviews as Topic , Lung Diseases/epidemiology , Male , Middle Aged , Neoplasms/epidemiology , Office Visits/statistics & numerical data , Outpatients/statistics & numerical data , Prognosis , Prospective Studies , Recurrence , Survival Analysis , Survival Rate , Treatment Outcome , Ventricular Fibrillation/mortality , Ventricular Fibrillation/therapy , Washington/epidemiologyABSTRACT
We have previously shown that glucocorticoids accelerate depolarization-induced 45Ca2+ influx in synaptosomes isolated from rat cerebral cortex, indicating that the steroids may modulate voltage-dependent Ca2+ channels. The present study was undertaken to characterize the biochemical action of glucocorticoids on dihydropyridine-sensitive voltage-dependent Ca2+ channels known to be present in brain synaptosomes. The [3H]dihydropyridine labeled site was used as a marker to determine the levels of functional Ca2+ channels. No effect on equilibrium binding of [3H]PN 200-110 was found when membranes from disrupted synaptosomes were incubated with corticosterone as high as 1 microM. However, when intact synaptosomes were first incubated with corticosterone at 37 degrees C and then disrupted, a significant increase in [3H]PN 200-110 binding was found. Steroid incubation of synaptosomes at 0 degree C was ineffective. It appears that metabolic processes requiring intracellular factors were involved in the steroid action. In examining this possibility, [3H]PN 200-110 binding was activated in disrupted membranes by MgATP and Ca(2+)-calmodulin, and corticosterone was found to enhance the activation in a concentration-dependent manner. [3H]PN 200-110 binding to membranes was also activated by incubation with MgATP and cAMP-dependent protein kinase, but this activation was not enhanced by the steroid. These findings are consistent with the interpretation that the steroid promotes Ca2+ channel activity by enhancing calmodulin-dependent activation of the channels. The action on voltage-dependent Ca2+ channels in synaptic terminals may well be a mechanism whereby glucocorticoids modulate neuronal activity.
Subject(s)
Calcium Channels/physiology , Cerebral Cortex/physiology , Glucocorticoids/pharmacology , Synapses/physiology , Synaptosomes/physiology , Adenosine Triphosphate/pharmacology , Animals , Binding, Competitive , Calcium Channel Blockers/metabolism , Calcium Channels/drug effects , Calcium Channels/metabolism , Calcium Channels, L-Type , Cell Membrane/drug effects , Cell Membrane/physiology , Cyclic AMP/pharmacology , Dihydropyridines/metabolism , Isradipine/metabolism , Kinetics , Male , Nerve Tissue Proteins/drug effects , Nerve Tissue Proteins/physiology , Rats , Rats, Sprague-Dawley , Steroids/pharmacology , Synapses/drug effects , Synaptosomes/drug effectsABSTRACT
This study was undertaken to investigate the biochemical events underlying the inhibitory action of ethanol on dihydropyridine-sensitive voltage-dependent Ca2+ channels in brain synaptosomes. The binding of radiolabeled dihydropyridine was used to determine functional Ca2+ channels in synaptosomes following exposure to ethanol. No effect on [3H]PN 200-110 binding was found when disrupted synaptosomal membranes were incubated with ethanol concentrations as high as 300 mM, suggesting that ethanol did not interact directly with sites on or near the Ca2+ channels. However, when intact synaptosomes were first incubated with ethanol (100 mM) at 37 degrees and then disrupted, a significant reduction in membrane binding of [3H]PN 200-110 was found. Ethanol incubation of synaptosomes at 0 degree was ineffective. It appears that metabolic processes involving intracellular factors were required in the ethanol action. In examining this possibility, [3H]PN 200-110 binding was activated by incubation of disrupted membranes with MgATP and Ca(2+)-calmodulin, and ethanol was found to inhibit the activation in a concentration-dependent manner (50-200 mM). [3H]PN 200-110 binding to membranes was also activated by incubation with MgATP and cyclic AMP-dependent protein kinase, but this activation was not inhibited by ethanol. These findings are consistent with the interpretation that ethanol acts on Ca2+ channels by inhibiting calmodulin-dependent activation of the channels.
Subject(s)
Brain/drug effects , Calcium Channel Blockers/pharmacology , Calcium Channels/drug effects , Dihydropyridines/metabolism , Ethanol/pharmacology , Synaptosomes/drug effects , Adenosine Triphosphate/pharmacology , Alcoholism/metabolism , Animals , Binding Sites , Brain/metabolism , Calcium Channels/metabolism , Cyclic AMP/pharmacology , Dihydropyridines/pharmacology , Isradipine/metabolism , Magnesium/pharmacology , Male , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity , Synaptosomes/metabolism , TritiumABSTRACT
The objective of the study was to compare the acceptability to semi-trained US American and Asian palatability panelist, of four wheat products processed to be possible replacers of rice in human diets. Products evaluated using rice as the control standard of excellence were steamed whole wheat, couscous (steamed, extracted wheat flour semolina), rosamarina (rice shaped, extracted wheat flour pasta), and bulgar (steamed, pre-cooked partly debranned, cracked wheat). Using a ten point hedonic rating scale, both groups of panelists gave rosamarina closely followed by couscous, most favorable ratings although these ratings were somewhat lower than that of the positive control, steamed polished rice. Bulgar wheat was given the lowest evaluation and was, in general, found to be an unacceptable replacement for rice by both American and Asian judges because of its dark, 'greasy' color and distinctive flavor. In their personal dietaries, judges included rice from 0.25 to 18 times per week with the Asian judges consuming rice significantly more times per week than did the American judges (10.8 +/- 4.71 vs 1.75 +/- 1.65, p < 0.01). However, rice consumption patterns, nationality, race, or sex of the judges was not demonstrated to affect scoring of the wheat products as rice replacers.
Subject(s)
Food Preferences , Oryza , Triticum , Asian , Cooking , Diet , Humans , Oryza/supply & distribution , Triticum/supply & distribution , United StatesABSTRACT
The objective of the project was to determine the bioavailability of selected B vitamins (niacin, pantothenic acid and thiamin) to humans from wet and dry milled maize brans which were coarsely or finely ground. Using a double cross-over design, the nine subjects were fed laboratory controlled diets containing unsupplemented bread or bread supplemented with finely ground, wet milled maize bran; coarsely ground, wet milled maize bran; finely ground, dry milled corn bran; or coarsely ground, dry milled maize bran. Subjects made complete collections of urine throughout the study which were analyzed for contents of the test vitamins. Although varying somewhat among vitamins, in general, better apparent bioavailability was achieved with the finely ground, dry milled maize bran than with the other test brans.
Subject(s)
Food Handling , Niacin/pharmacokinetics , Pantothenic Acid/pharmacokinetics , Thiamine/pharmacokinetics , Zea mays/metabolism , Adult , Biological Availability , Bread , Female , Humans , Intestinal Absorption , Male , Niacin/urine , Nutritive Value , Pantothenic Acid/urine , Particle Size , Thiamine/urineABSTRACT
Survival rates and antiarrhythmic drug use were determined in 941 consecutive patients resuscitated from prehospital cardiac arrest due to ventricular fibrillation between March 7, 1970, and March 6, 1985. Of these patients, 18.7% were treated for at least a portion of the period with quinidine, 17.5% with procainamide, and 39.4% received no antiarrhythmic agent. Beta blockers were prescribed for 28.3% of the patients. Unadjusted comparisons of survival estimates showed dramatically lower survival rates for patients who received antiarrhythmic drugs independent of beta-blocker therapy and significantly improved survival for patients receiving beta-blocker therapy independent of antiarrhythmic use. Patients for whom antiarrhythmic therapy was prescribed also had more adverse baseline risk factors, whereas patients taking beta blockers had fewer such risk factors. After adjustment for these baseline risk factors, the use of antiarrhythmics was weakly (p less than 0.09) associated with worsened survival; 2-year survival for procainamide-treated patients was 30% and quinidine-treated patients 55% (p = 0.003). Beta-blocker therapy was associated with improved (p less than 0.001) survival. Thus, although neither procainamide nor quinidine appear to have had a benefit on mortality, the effect of procainamide appears to be significantly worse than that of quinidine. The use of antiarrhythmic drug therapy in patients resuscitated from prehospital ventricular fibrillation should be regarded as not only unproved, but potentially hazardous, and should probably be restricted to testing in randomized clinical trials.