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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 163 records · Page 9Linked to original sources

Circulating L-selectin in multiple sclerosis patients with active, gadolinium-enhancing brain plaques.

Leukocyte migration into inflammatory lesions is controlled by adhesion molecules. L-selectin is the adhesion molecule on leukocytes that is responsible for making the initial contact with endothelium. After establishing this contact, L-selectin is shed from the cell surface and present in the circulation as a functional soluble receptor. To investigate this initial adhesive event, we evaluated the presence of soluble L-selectin (sL-selectin) in serum and CSF of patients with multiple sclerosis (MS), viral encephalitis, and controls. MS patients with active, gadolinium-enhancing lesions on magnetic resonance imaging had significantly higher sL-selectin serum levels than controls (P < 0.05). These levels in MS patients correlated with the size of the enhancing lesions (P < 0.05), and with sL-selectin levels in CSF (P < 0.001). In viral encephalitis, in contrast, sL-selectin is elevated in CSF only (P < 0.001) and may derive from intrathecal leukocytes. These results show that the earliest adhesive events mediated by L-selectin indeed operate in active MS, and that sL-selectin will be of value in quantitating the extent of this inflammatory process.

Adult↗

Functional MR imaging of semantic information processing and learning-related effects using psychometrically controlled stimulation paradigms.

Functional magnetic resonance imaging (fMRI), in conjunction with carefully designed, psychometrically optimized stimulation procedures, was used to investigate the relation between brain activation and the processing of word associations. A semantic discrimination task of word-pair similarity was performed by normal subjects (n = 17) within a clinical 1.5-Tesla whole-body MRI system. A color similarity task of psychometrically equivalent difficulty, as indicated by behavioral data acquired online during fMRI, served as active control condition. Comparisons between tasks dramatically improved results compared to comparisons between task and resting condition. The language paradigm selectively activated left frontal and left fronto-temporal areas. Cortical activation during the semantic task decreased significantly over three runs of the same word list and was paralleled by decreased reaction times. No such changes were observed in the active control condition indicating selective learning of the language task only. When combined with psychological activation schemes and the acquisition of behavioral data, fMRI represents a powerful tool for the study of brain-behavior interaction.

Adult↗

Epithelioid hemangioendothelioma of the lumbar vertebral column: case report and review of literature.

Epithelioid hemangioendothelioma is a recently described, rare vasoformative vascular tumor of variable biological behavior. Its principal sites of occurrence are soft tissues, liver, lung, and bone. There have been no formal case reports of this tumor occurring in the vertebral column, and there are no reports in the literature of surgical treatment for vertebral epithelioid hemangioendothelioma. We present a case of primary vertebral epithelioid hemangioendothelioma occurring in the L2 vertebral body. Surgical treatment, pathological findings, imaging characteristics, and a review of the literature are presented.

Adult↗

In vivo replication of hamster polyomavirus DNA displays lymphotropism in hamsters susceptible to lymphoma induction.

Using the whole body section hybridization technique, we monitored the organ- and age-specific pattern of replication of hamster polyomavirus (HaPV) DNA in a colony of Syrian hamsters, which are susceptible to lymphoma induction. Three phases of viral infection and replication could be distinguished: first, a phase of acute infection characterized by high levels of replication of HaPV DNA in the haemopoietic organs and the liver. This culminated 5 to 7 days post-infection (p.i.); second, at 10 days p.i., a phase of viral clearance became evident; and finally, a third phase reflected both the restriction of HaPV replication in adult hamsters and the accumulation of HaPV DNA at sites of tumour development. A remarkable conformity was observed between the tissue specificity of viral replication and the induced tumour profile: high levels of replication of HaPV DNA were restricted to cells of the haemopoietic system and lymphoid tumours were induced. As shown by in situ hybridization, the viral infection in non-haemopoietic organs was due to the dissemination of HaPV-infected blood cells.

Animals↗

Intravascular ultrasound imaging of human cerebral arteries.

The aim of this study was to assess the feasibility of imaging cerebral arteries in vitro with intravascular ultrasound and to establish a correlation between echographic images and corresponding histological architecture. Intravascular ultrasound imaging was performed using a 30-MHz, 4.3F ultrasound probe. Twenty-two arterial segments were obtained at autopsy from 6 patients and were imaged fresh. Arteries were then processed for histological examination and comparisons were made between echographic and histological findings. The correlation between luminal area measurements as determined histologically and by intravascular ultrasound was tested by linear regression analysis. Intravascular ultrasound demonstrated a three-layered appearance in normal cerebral arteries but not in those affected by severe atherosclerosis. Overall, ultrasound correctly identified the presence of a plaque in 83% of patients. Intravascular ultrasound sensitivity and specificity, respectively, were 100 and 80% for calcium deposits and 83 and 75% for fibrous tissue. Intravascular ultrasound and histological measurements correlated well for the determination of luminal area (r = 0.89). Intravascular ultrasound provides accurate characterization of the arterial lumen and geometry, as well as the presence and histological features of atherosclerotic plaque. Thus, it appears to have a great potential for an earlier and more accurate diagnosis of atherosclerosis and may serve to guide new interventional techniques being utilized in the treatment of cerebrovascular diseases.

Aged↗

Modified control of breathing in genetically obese (ob/ob) mice.

Attenuated hypercapnic chemosensitivity and hypoventilation are characteristics periodically associated with human obesity. We tested the hypothesis that ventilatory control is altered by genetic determinants and age-dependent factors that influence the obese phenotype. To this end, the magnitude and pattern of breathing were examined before and associated with the development of obesity in C57BL/6J mice homozygous and heterozygous at the ob gene locus. Breathing frequency and tidal volume were measured using whole body plethysmography, and minute ventilation was assessed during acute hypoxic and hypercapnic challenges with intermittent room air exposures. In age- and weight-matched mice before pronounced obesity, significant (P < 0.05) reductions in hypercapnic ventilatory sensitivity occurred in mutant (ob/ob) mice relative to wild-type (+/+) homozygotes primarily because of an attenuated tidal volume. Longitudinal studies indicated that mutant ob mice developed rapid baseline breathing relative to the wild type, accompanying a twofold greater increase in body mass. Early differences between homozygotes in hypercapnic ventilatory sensitivity were maintained through 230 days. These data demonstrate that genetic determinants at or closely linked to the ob locus influence hypercapnic ventilation before the emergence of pronounced obesity, whereas changes in baseline breathing appear due to age-dependent increases in body weight.

Aging↗

Assessment of regional cerebral blood volume in acute human stroke by use of single-slice dynamic susceptibility contrast-enhanced magnetic resonance imaging.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the clinical usefulness of dynamic susceptibility contrast-enhanced MRI (DSC-MRI) in acute cerebral ischemia. METHODS: During bolus injection of gadolinium-diethylenetriamine pentaacetic acid, a series of rapid T2*-weighted images was recorded from one slice. Concentration-time curves and images of regional cerebral blood volume (rCBV) were calculated from this data set. DSC-MRI, MR angiography, conventional spin-echo MRI (SE-MRI), and CT were performed in 11 patients within 6 hours after stroke onset and before thrombolytic or anticoagulant treatment was begun. A follow-up MRI examination was performed 24 to 48 hours after stroke onset. RESULTS: In 7 of 11 patients (group 1) with territorial infarcts of the middle (n = 6) or posterior cerebral artery (n = 1), DSC-MRI showed reduced rCBV in the affected territory before conventional SE-MRI displayed ischemic lesions. DSC-MRI was helpful to differentiate severely ischemic tissue from peri-infarct parenchyma. Partial reperfusion (n = 3), unchanged reduction of rCBV (n = 2), and progressive reduction of rCBV (n = 2) were observed in the follow-up study. Normal DSC-MRI findings were present in 4 of 11 patients (group 2) with lacunar infarcts. CONCLUSIONS: DSC-MRI accomplished the detection of the ischemic territory in the very early stage (< 6 hours) before SE-MRI delivered unequivocal results. DSC-MRI might be helpful to discriminate completely ischemic tissue from potentially salvageable ischemic parenchyma at risk and may play an important role in stroke therapy and evaluation.

Aged↗

Comparison of the Electromechanical Effects of Vesnarinone and Amrinone in Isolated Dog Purkinje Strands and Ventricular Trabeculae.

BACKGROUND: Conventional microelectrode techniques were used to compare the concentration-dependent effects of vesnarinone (0.1-100 µM) and amrinone (1 µM-1 mM) on action potential duration (APD) and developed force in both isolated dog ventricular trabeculae and Purkinje strands. METHODS AND RESULTS: Both drugs increased contractility of trabecular muscle preparations, while, in Purkinje strands, vesnarinone failed to increase developed force during continuous pacing at 2 Hz. Vesnarinone lengthened APD in both preparations; although this effect was more marked in Purkinje strands. Ventricular muscle APD was not affected by amrinone (1 µM to 1 mM), while, in Purkinje strands, amrinone produced a biphasic effect on APD. Low concentrations (1-100 µM) of amrinone shortened Purkinje fiber APD, while only the highest concentration (1 mM) used lengthened APD. In addition, in Purkinje strand preparations the effects of vesnarinone (10 µM) on APD and developed force were proportional to pacing cycle length at frequencies slower than 2 Hz; however, at frequencies faster than 2 Hz vesnarinone decreased developed force while APD was lengthened. In ventricular trabecular muscle preparations, the effects of vesnarinone were not affected by frequency. CONCLUSIONS: These results indicate clear differences between the effects of vesnarinone and amrinone in isolated cardiac preparations. These differences in experimental effects in isolated cardiac preparations may help provide an explanation for the disappointing clinical response of patients in heart failure to amrinone, while vesnarinone has appeared to be beneficial.

Journal Article↗

Reduction of Carnitine Content by Inhibition of Its Biosynthesis Results in Protection of Isolated Guinea Pig Hearts Against Hypoxic Damage.

BACKGROUND: 3-(2,2,2-trimethylhydrazinium) propionate (THP or mildronate) is an inhibitor of carnitine biosynthesis. This study was carried out to determine whether feeding of guinea pigs with THP results in decreased myocardial-free carnitine content and, as a result, attenuates hypoxic damage in isolated and paced work-performing hearts. METHODS AND RESULTS: Guinea pigs were administered either distilled water of 100 mg THP/kg/day orally for 10 days. The treatment resulted in about a 50% decline in myocardial-free carnitine content, from 11.1 +/- 0.2 (n = 5) to 5.6 +/- 0.2 (n = 5) µM/g dry weight of the heart. The left ventricular contractile function of the hearts was measured during normoxic perfusion (PO(2) = 590 mmHg), hypoxic perfusion (PO(2) = 149 mmHg), and reperfusion (PO(2) = 590 mmHg). In both untreated and THP-treated groups, the rate of development of intraventricular pressure (+dP/dt) under normoxic perfusion was similar; however, +dP/dt declined to about 10% of the initial rate within 20 minutes of hypoxic perfusion. In the THP-treated group of hearts, the initial decline was slower than that of the untreated animal hearts. After 20 minutes of normoxic reperfusion following 60 minutes of hypoxic perfusion, the recovery of +dP/dt and -dP/dt was greater in the THP-treated group than in the untreated group. The elevation of end-diastolic pressure during hypoxia was completely reversed by normoxic reperfusion of the THP-treated group but not in the untreated group. Mitochondria isolated from hearts from the THP-treated group after normoxic reperfusion following hypoxic perfusion exhibited better respiratory function than those from untreated hearts. CONCLUSIONS: The data suggest that feeding guinea pigs with THP results in reduced myocardial-free carnitine content and attenuation of hypoxic and reperfusion injury in isolated hearts.

Journal Article↗

Molecular pharmacology of voltage-dependent calcium channels.

Voltage-dependent Ca2+ channels serve as the only link to transduce membrane depolarization into cellular Ca(2+)-dependent reactions. A wide variety of chemical substances that have the ability to modulate Ca2+ channels have been demonstrated both for their clinic utility and for importance in elucidating the molecular basis of various biological responses. Recently, introduction of molecular biology to pharmacology has brought a great deal of information about the molecular basis of drug action in Ca2+ channels. In this review, we attempt to overview recent progress in understanding the interactions between Ca2+ channels and their blockers, namely Ca2+ antagonists, from a molecular and structural point of view.

Agatoxins↗

The consequences of drug use/abuse for vocational career: a longitudinal study of a male urban African-American sample.

This report is from a longitudinal study of a community sample of African-American males (N = 197) on the relationship of the degree of earlier substance use/abuse up to average age 24, to vocational performance (employment and occupational level) 2 1/2 years later (at average age 26 1/2). The statistical analyses included numerous control variables developed from prospective data of the National Collaborative Perinatal Project, on the subjects and on their families from the subjects' birth to age 7, and from their school behavior and academic performance up to age 16, which may have influenced their vocational-occupational behavior during early adulthood. It was found that greater earlier marijuana use and greater earlier alcohol use predicted, to a significant degree, poorer occupational performance.

Adult↗

Clinical significance of diffuse dural enhancement detected by magnetic resonance imaging.

This study was performed to determine the clinical significance of diffuse dural enhancement (DDE) detected by magnetic resonance (MR) imaging and to typify enhancing patterns related to inflammatory or metastatic causes. The authors retrospectively evaluated the clinical, imaging, and laboratory characteristics of 20 consecutive patients with DDE. Those with DDE and an underlying neoplastic disease (13 patients) were compared to 11 consecutive patients with cytological evidence of neoplastic leptomeningeal metastasis evaluated by MR imaging. The DDE was often associated with an underlying malignancy (13 (65%) of 20 patients) but it coexisted with leptomeningeal metastasis in only one patient. Skull metastases were evident in 10 (77%) of 13 patients and cranial nerve palsies in six (46%) of 13. Other causes of DDE were related to cerebrospinal fluid (CSF) leak or shunting (five (25%) of 20), with or without symptoms of intracranial hypotension, and to dural sinus thrombosis and pachymeningitis. Dural biopsies obtained in two patients with DDE showed a narrow rim of granulation-like tissue adherent to the dural surface facing the inner skull table. Magnetic resonance subtraction, diffusion, and perfusion studies revealed unique characteristics in patients with metastatic causes as compared to those with DDE secondary to CSF leak. None of the patients with proven leptomeningeal metastasis had DDE, but four of them presented with focal dural enhancement and two displayed apparent leptomeningeal enhancement. The findings indicate that DDE is not a radiographic hallmark of leptomeningeal metastasis in spite of the similarities in clinical manifestations (for example, headache and cranial polyneuropathy). Nonetheless, DDE is most frequently associated with metastatic malignancies and particularly with skull metastases and CSF leak. Special MR techniques can discern the underlying cause and elucidate the disparity in the pathophysiological mechanisms leading to DDE.

Aged↗

The spectrum of brain MR abnormalities in sickle-cell disease: a report from the Cooperative Study of Sickle Cell Disease.

PURPOSE: To define the spectrum of abnormalities in sickle-cell disease, including infarction, atrophy, and hemorrhage, that are identified by brain MR imaging. METHODS: All MR studies included T1, T2, and intermediate pulse sequences. Images were interpreted without knowledge of the clinical history or neurologic examination findings. Brain MR imaging was performed in 312 children with sickle-cell disease. RESULTS: Seventy patients (22%) had infarction/ischemia and/or atrophy, infarction/ischemia was noted in 39 children (13%) who had no history of a stroke (the "silent" group). The prevalence rates for silent lesions were 17% for sickle-cell anemia and 3% for hemoglobin sickle-cell disease. For patients with sickle-cell anemia and a history of cerebrovascular accident, infarction/ischemia lesions typically involved both cortex and deep white matter, while silent lesions usually were confined to deep white matter. Within the age range studied, the prevalence of infarction/ischemia did not increase significantly with age, although older patients with lesions had more lesions than did younger patients with lesions. CONCLUSIONS: Brain MR imaging showed infarction/ischemia in the absence of a recognized cerebrovascular accident in 13% of patients. The prevalence of these lesions did not increase significantly between the ages of 6 and 14 years, suggesting that lesions are present by age 6. However, the increase in the average number of lesions per patient with age may indicate progressive brain injury.

Adolescent↗

Concerns, affect, and cognitive disruption following completion of radiation treatment for localized breast or prostate cancer.

PURPOSE/OBJECTIVES: To describe concerns, cognitive disruption, and affect following the completion of radiation treatment (RT) for localized breast or prostate cancer. DESIGN: Cross-sectional, descriptive. SETTING: Two RT centers associated with a university hospital. SAMPLE: Patients who completed RT for prostate (n = 9) or breast cancer (n = 11). The mean age of the sample is 64 years. Ninety percent are Caucasian, 80% are married, 50% are of Latter-day Saint faith, and 50% are retired. All had early stage disease, with a mean of 20 months post-RT. METHODS: One-time interview using qualitative methods and the Life Orientation Test, Revised Impact of Events Scale, state scale of the Positive and Negative Affect Schedule, satisfaction items of the Sarason Social Support Questionnaire, and Side Effect Severity Checklist. MAIN RESEARCH VARIABLES: Frequency of intrusive thoughts or avoidant behavior, positive and negative affect, dispositional optimism, satisfaction with social support, severity of side effects, and themes extracted from semistructured interviews. FINDINGS: Most subjects had unexpected intrusive thoughts about cancer; more than one-third avoided reminders of cancer. The level of positive affect was high, as was optimism. The level of negative affect was low. Subjects' satisfaction level with social support was high. Fatigue was the most frequently reported continuing side effect. Relative optimism, acceptance, vigilance, and trust of healthcare providers were major themes. Avoidance, comparison, maintaining normalcy, and information seeking were common coping strategies. CONCLUSIONS: Subjects perceived themselves to be doing well. Fatigue was the most common long-term side effect. Subjects continued to seek information. Symptom vigilance and interpretation were important, as were having a positive outlook and maintaining normalcy. IMPLICATIONS FOR NURSING PRACTICE: Nurses must acknowledge the potential for concerns about symptoms and continuing side effects and what they mean for the patient. Clinicians need to provide accurate information about common post-treatment experiences. Clinicians also must remember that subjects have vivid recollections of both positive and negative interactions with healthcare providers.

Adaptation, Psychological↗

Binding sites of monoclonal antibodies and dihydropyridine receptor alpha 1 subunit cytoplasmic II-III loop on skeletal muscle triadin fusion peptides.

Triadin binds to the dihydropyridine receptor (DHPr) and the junction foot protein (JFP) in Western blot protein overlay experiments. Fusion peptides were synthesized using an expression system, pGSTag, which includes a protein kinase A phosphorylation site. Expressed peptides are DHPr664-799 encoding rabbit skeletal DHPr alpha1 subunit amino acids 664-799, triadin 1 (1-49), triadin 2 (68-389), triadin 2' (110-389), triadin 2a (68-278), triadin 2a1 (67-163), triadin 2a2 (165-240), triadin 2b (242-389), triadin 2b1 (242-299), triadin 3 (370-706), triadin 3a (370-562), triadin 3b (551-706), triadin 3b1 (551-672), and triadin 3b2 (673-706) (the numbers in parentheses correspond to the amino acid sequence of triadin). The triadin monoclonal antibodies, GE4.90 and AE8.91, bind to intact triadic vesicles as well as to vesicle fragments prepared after treatment with Triton X-100, indicating that they have cytoplasmic epitopes. MAb AE8.91 binds to triadin 2, 2', 2a, and 2a1, while mAb GE4.90 binds to triadin 3, 3b, and 3b2 indicating that residues 110-163 and the C-terminal 34 amino acids contain cytoplasmic domains. Radiolabeled DHPr664-799 binds to triadin in intact vesicles under nonreducing and reducing conditions. It binds to triadin fusion peptides, triadin 2, 2a, 3, 3b, and 3b1, but no to triadin 1 or triadin 3b2. The binding to triadin 2a is the most prominent. Direct binding between DHPr-644-799 and JFP was not seen. These experimental findings indicate that triadin contains an extensive cytoplasmic domain that binds to the domain of DHPr which is considered critical for signal transmission during skeletal muscle excitation-contraction sampling.

Amino Acid Sequence↗