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Biomedical subjects

A Friedman

Publications and source records attributed to A Friedman.

At least 91 records · Page 5Linked to original sources
PubMed1996

Iron in parkinsonian and control substantia nigra--a Mössbauer spectroscopy study.

We used Mössbauer spectroscopy to study the iron content, the redox state, and the binding site of iron in substantia nigra (SN) from parkinsonian (PD) and control brains. Measurements performed on fresh-frozen, formalin-fixed, and lyophilized samples demonstrated the presence of ferric (Fe3+) iron only, both in PD and control SN. Ferrous iron, if present at all, may represent at most 5% of the total iron. We found no difference in the total amount of iron in SN between PD and control brains. The Mössbauer spectra observed at 4.1 K in fresh (frozen or lyophilized) samples were different from those obtained in formalin-fixed (frozen or lyophilized) samples. In the fresh samples, only ferritin-like iron was observed, whereas in the samples frozen or lyophilized from formalin, non-ferritin iron was detected.

Aged↗
PubMed1996

Differences between employed and nonemployed dialysis patients.

Three hundred fifty-nine chronic dialysis patients (85 employed and 274 nonemployed) were surveyed to identify/verify those characteristics which differentiate between employed versus nonemployed status. Education emerged as a significant correlate of employment, as noted by previous investigators, whereas, unlike previous research, neither mode of dialysis, length of time on dialysis, number of comorbid conditions, nor cause of renal failure (eg, diabetes) were associated with employment status. Measures of functional status (MOS SF-20 and Karnofsky) were positively associated with employment. Furthermore, patients' perceptions that their health limited the type and amount of work that they could do were negatively associated with employment. In addition, using a series of de novo items, we found subjects' beliefs about dialysis patients' ability to work to be a "self-fulfilling prophecy" with regard to employment status. That is, patients who themselves believed that dialysis patients should work and had this notion reinforced by significant others were more likely to be employed. Interestingly, 21 percent of unemployed patients reported that they were both able to work and wanted to return to work. Because it is consistently reported that only a small percentage of dialysis patients are employed, targeting the patients who are both willing and able to work for vocational rehabilitation might significantly increase the numbers of employed dialysis patients.

Adolescent↗
PubMed1996

Pyridostigmine brain penetration under stress enhances neuronal excitability and induces early immediate transcriptional response.

Pyridostigmine, a carbamate acetylcholinesterase (AChE) inhibitor, is routinely employed in the treatment of the autoimmune disease myasthenia gravis. Pyridostigmine is also recommended by most Western armies for use as pretreatment under threat of chemical warfare, because of its protective effect against organophosphate poisoning. Because of this drug's quaternary ammonium group, which prevents its penetration through the blood-brain barrier, the symptoms associated with its routine use primarily reflect perturbations in peripheral nervous system functions. Unexpectedly, under a similar regimen, pyridostigmine administration during the Persian Gulf War resulted in a greater than threefold increase in the frequency of reported central nervous system symptoms. This increase was not due to enhanced absorption (or decreased elimination) of the drug, because the inhibition efficacy of serum butyryl-cholinesterase was not modified. Because previous animal studies have shown stress-induced disruption of the blood-brain barrier, an alternative possibility was that the stress situation associated with war allowed pyridostigmine penetration into the brain. Here we report that after mice were subjected to a forced swim protocol (shown previously to simulate stress), an increase in blood-brain barrier permeability reduced the pyridostigmine dose required to inhibit mouse brain AChE activity by 50% to less than 1/100th of the usual dose. Under these conditions, peripherally administered pyridostigmine increased the brain levels of c-fos oncogene and AChE mRNAs. Moreover, in vitro exposure to pyridostigmine increased both electrical excitability and c-fos mRNA levels in brain slices, demonstrating that the observed changes could be directly induced by pyridostigmine. These findings suggest that peripherally acting drugs administered under stress may reach the brain and affect centrally controlled functions.

Acetylthiocholine↗
PubMed1996

Peripheral tolerance of Th2 lymphocytes induced by continuous feeding of ovalbumin.

We established conditions for inducing antigen-specific tolerance in Th2 lymphocytes by means of oral tolerance. Mice were continuously exposed to ovalbumin in their drinking water for a minimal period of 20 days and then immunized against antigen in either complete Freund's adjuvant or Al(OH)3. This feeding regimen tolerized both Th2 and Th1 responses as shown by diminished proliferation, cytokine secretion (IL-4, IL-2 and IFN-gamma) and specific cytokine mRNA expression (IL-4, IL-2 and IFN-gamma) in vitro, as well as by absence of specific antibody production (IgG1, IgG2a, IgG2b and IgE) in vivo. Conditions for generating Th2 lymphocyte tolerance were different from those required to generate tolerance in Th1 lymphocytes: these included extended, continuous exposure to high dosages of antigen, rather than a single or intermittent feeding regimen which was sufficient to induce tolerance in Th1 lymphocytes. These findings suggest that continuous oral exposure to a tolerogen may be a biologically relevant strategy to tolerize both Th1- and Th-dependent responses, and extend the potential clinical use of oral tolerance to ailments mediated by Th2 lymphocytes.

Administration, Oral↗
PubMed1996

Therapeutic effects of estradiol benzoate on development of collagen-induced arthritis (CIA) in the Lewis rat are mediated via suppression of the humoral response against denatured collagen type II (CII).

The effects of estradiol benzoate (EB) on the development of anti-CII antibodies and their pathogenic potential were studied during the progress of established CIA in the rat. CIA was induced in mature female Lewis rats by two subcutaneous inoculations containing bovine native CII (BCIIn), emulsified in Freund's incomplete adjuvant. Clinical arthritis fully developed by day 18 and then EB (1 mg/kg body wt per day, diluted in corn oil (CO)) was administered intramuscularly every second day thereafter. Antibodies binding four different CIIs (bovine or rat, either native or heat-denatured) were detected in sera and joint tissue extracts by means of solid-phase ELISA. Pharmacological doses of EB (>0.2 mg/kg body wt per day) caused significant remission of established CIA 5-7 days after treatment, and selectively suppressed the production of antibodies specific for denatured CII. To evaluate the arthritogenic potential of circulating anti-CIId IgG, transfer experiments were performed. IgG anti-CIIn, purified from EB-treated CIA rats, was not arthritogenic, whereas IgG anti-denatured (CIId), purified from CO-treated CIA rats, caused severe passive arthritis. Furthermore, pretreatment with rat CIId protected against subsequent induction of CIA, and this protection was associated with suppressed antibody production against CIId. Collectively, our results indicate that antibodies specific for CIId are involved in the pathogenesis of CIA, and that oestrogen-related remission of clinical arthritis may by caused by a selective suppression of antibodies produced against degraded/denatured CII.

Animals↗
PubMed1996

Regulation of endothelin-1 expression in the bovine corpus luteum: elevation by prostaglandin F 2 alpha.

Prostaglandin F2alpha (PGF2alpha) has been recognized as the physiological luteolysin in ruminants and other species for more than three decades; however, the mechanisms involved in its action are poorly understood. We previously have shown that endothelin-1 (ET-1) mediates, at least in part, the action of PGF2alpha, and the current study examines the effect of PGF2alpha on the expression of ET-1 in bovine corpus luteum (CL). Endothelins (ETs) were extracted from CL, collected at various times of the estrous cycle, and highest levels were found during luteolysis. The expression of prepro-ET-1 was also highest in regressing CL, suggesting that PGF2alpha may have elevated ET-1 expression. This was confirmed by demonstrating that administration of PGF2alpha to heifers at midcycle elevated luteal ET-1 expression. Levels were induced as soon as 2 h after PGF2alpha treatment and 24 h later were 7-fold higher than preinjection levels. Endothelial cells isolated from bovine CL produced ET-1, and addition of PGF2alpha, oxytocin (OT), and vasopressin-augmented ET biosynthesis. Induction of ET-1 expression by PGF2alpha in these cells was evident after a short incubation time (15-90 min). Taken together, these data suggest that stimulation of luteal ET-1 expression by PGF2alpha may be achieved by several nonmutually exclusive mechanisms: 1) by acting directly on luteal endothelial cells; 2) indirectly, via OT release from large luteal cells; and 3) by causing hypoxia in the CL (as a result of ET-1-induced vasoconstriction). The latter mechanism may serve to augment ET-1 secretion in a positive-feedback process.

Animals↗
PubMed1996

The importance of being upright: use of environmental and viewer-centered reference frames in shape discriminations of novel three-dimensional objects.

We investigated the frame of reference that people use to make shape discriminations when their heads are either upright or tilted. Observers made same-different judgments of pairs of novel three-dimensional objects that were aligned along their length within the frontal-parallel plane and rotated in depth around an axis parallel to their own axes of elongation. The aligned objects were displayed vertically, tilted 45 degrees, or horizontally with respect to the environmental upright, but the distance of each pair from the upright was irrelevant to resolving the angular disparity between the stimuli for the same-different judgment. Nevertheless, when observers' heads were upright, the time to encode the stimuli was a linear function of the distance of the stimuli from the environmental upright, whereas when observers' heads were tilted 45 degrees, encoding times for tilted and vertical stimuli did not differ and were faster than the times to encode horizontal stimuli. We interpreted these data to mean that observers either rotate or reference the top of an object to the environmental upright, and they can use either a gravitational or retinal reference frame to do so when either they or the objects are not upright.

Decision Making↗
PubMed1996

Nutritional management of the child with mild to moderate chronic renal failure.

1. The best way to prevent early growth failure in children with renal disease is by the use of specified nutrition and appropriate buffer, activated vitamin D, and calcium-containing phosphate binders as needed. With prenatal diagnosis of anatomically abnormal kidneys available, this type of early intervention may be much more feasible in the 1990s. 2. Supplemental sodium and water in children with polyuria and intravascular volume depletion may prevent growth failure. Cow milk is detrimental in this group of individuals because of high solute and protein load, often causing intravascular volume depletion, hyperphosphatemia, and acidosis. 3. Children with acquired glomerular disease may need sodium restriction and, if treated with steroids, a diet low in saturated fat. 4. Children with nephrotic syndrome and severe edema should be evaluated for malabsorption and subsequent malnutrition. Protein intake should be supplemented only at the RDA and to replace ongoing losses. Long-term sodium restriction is appropriate. Hyperlipidemia should be monitored: if nephrosis is chronic, a low saturated fat diet should be instituted. Angiotensin-converting enzyme inhibitors can decrease urinary protein loss and may ameliorate hyperlipidemia. Children resistant to therapy can have very high morbidity. 5. Children with <50 % of normal creatinine clearance should have PTH measured and activated vitamin D therapy should be started if PTH is elevated more than two to three times normal. Thereafter careful monitoring of calcium, phosphorus, and PTH is crucial to prevent renal osteodystrophy, low turnover bone disease, and hypercalcemia with hypercalciuria and nephrocalcinosis. 6. Children with tubular defects with severe polyuria also may benefit from low-solute, high-volume feedings. 7. All physicians caring for children with renal disease should have pediatric nephrology consultation available. Prevention of growth failure is much more cost effective than pharmacologic therapy. Before initiating growth hormone treatment for growth retardation, assiduous treatment of co-existing renal osteodystrophy and provision of optimal nutritional intake should be accomplished.

Calcium↗
PubMed1995

Electrical consequences of spine dimensions in a model of a cortical spiny stellate cell completely reconstructed from serial thin sections.

We built a passive compartmental model of a cortical spiny stellate cell from the barrel cortex of the mouse that had been reconstructed in its entirety from electron microscopic analysis of serial thin sections (White and Rock, 1980). Morphological data included dimensions of soma and all five dendrites, neck lengths and head diameters of all 380 spines (a uniform neck diameter of 0.1 micron was assumed), locations of all symmetrical and asymmetrical (axo-spinous) synapses, and locations of all 43 thalamocortical (TC) synapses (as identified from the consequences of a prior thalamic lesion). In the model, unitary excitatory synaptic inputs had a peak conductance change of 0.5 nS at 0.2 msec; conclusions were robust over a wide range of assumed passive-membrane parameters. When recorded at the soma, all unitary EPSPs, which were initiated at the spine heads, were relatively iso-efficient; each produced about 1 mV somatic depolarization regardless of spine location or geometry. However, in the spine heads there was a twentyfold variation in EPSP amplitudes, largely reflecting the variation in spine neck lengths. Synchronous activation of the TC synapses produced a somatic depolarization probably sufficient to fire the neuron; doubling or halving the TC spine neck diameters had only minimal effect on the amplitude of the composite TC-EPSP. As have others, we also conclude that from a somato-centric viewpoint, changes in spine geometry would have relatively little direct influence on amplitudes of EPSPs recorded at the soma, especially for a distributed, synchronously activated input such as the TC pathway. However, consideration of the detailed morphology of an entire neuron indicates that, from a dendro-centric point of view, changes in spine dimension can have a very significant electrical impact on local processing near the sites of input.

Animals↗
PubMed1995

Risk of intracranial aneurysms in families with subarachnoid hemorrhage.

BACKGROUND: Genetic factors may be important in the etiology of subarachnoid hemorrhage (SAH) and intracranial aneurysm (IA) formation. Several studies have reported the familial occurrence of SAH and IA, although in most cases asymptomatic family members were not studied with elective angiography. The examination of data from large sibships could provide important information about the frequency of IA occurrence in at-risk individuals and the mode of inheritance for familial SAH/IA. METHODS: We reviewed published case series of sibships with SAH and at least four siblings, in which at least one sibling underwent elective angiography. Data were collected on age-of-onset, clinical events, presence of hypertension, angiographic findings, and outcome. Patients were classified as "affected" if they had a SAH or if an IA was detected by elective angiography, and "unaffected" if they were asymptomatic and had a negative angiogram. RESULTS: Seven case series with 52 individuals (26 men and 26 women) met our inclusion criteria. The sibships ranged from 6 to 13 members. Most of the siblings (32 of 52, 61%) were asymptomatic, 18 (35%) had a SAH, and 2 (4%) had focal symptoms but no SAH. Elective angiography of 34 siblings showed an IA in 11 (32%) and was negative in 23 (68%). The overall rate of affecteds (SAH or IA) was 56%. CONCLUSIONS: Based on data from these sibships, angiography of asymptomatic at-risk siblings demonstrated an IA in almost one-third of cases. Familial SAH/IA segregated with a pattern that was consistent with an autosomal dominant trait in this selected series of sibships, although other factors could produce these findings.

Adult↗
PubMed1995

Preclinical efficacy of a prototype DNA vaccine: enhanced protection against antigenic drift in influenza virus.

Vaccination with plasmid DNA expression vectors encoding foreign proteins elicits antibodies and cell-mediated immunity and protects against disease in animal models. We report a comparison of DNA vaccines, using contemporary human strains of virus, and clinically licensed (inactivated virus or subvirion) vaccines in preclinical animal models, to better predict their efficacy in humans. Influenza DNA vaccines elicited antibodies in both non-human primates and ferrets and protected ferrets against challenge with an antigenically distinct epidemic human influenza virus more effectively than the contemporary clinically licensed vaccine. These studies demonstrate that DNA vaccines may be more effective, particularly against different strains of virus, than inactivated virus or subvirion vaccines.

Animals↗
PubMed1995

The effect of varying dietary concentrations of vitamin A on immune response in the turkey.

1. The effect of dietary vitamin A on antibody production and T-cell proliferative response was determined in poults from 21 to 41 d old. Poults were fed on soyabean meal-sorghum-based diets with concentrations of supplemented vitamin A from 0 to 13.2 micrograms/g retinol equivalents from hatching and were immunised with Newcastle disease virus (NDV) and turkey pox vaccines. T-cell proliferation response to concanavlin A was determined in vitro at 31 d old. Antibodies to NDV and turkey pox in serum were determined at 10 and 20 d after inoculation. 2. Poults receiving the diet with no added dietary vitamin A died by 22 d and had very low concentrations of plasma and liver vitamin A. 3. Increasing dietary concentrations of vitamin A enhanced the proliferative response until the diet contained 6.0 micrograms/g, above which the response began to decrease. The antibody titres to NDV and turkey pox increased as dietary vitamin A increased, with maximal values found 10 d after inoculation with 6.0 micrograms/g. At 20 d after inoculation low antibody titres were found with low vitamin A intake. 4. These data suggest that maximal immune responses in the poult may be achieved at dietary intakes of vitamin A at or higher than those recommended by NRC (1984, 1994).

Analysis of Variance↗
PubMed1995

Predictors of between-method differences in cardiac output measurement using thoracic electrical bioimpedance and thermodilution.

OBJECTIVES: To evaluate the usefulness of transthoracic electrical bioimpedance in trending changes in cardiac output after cardiac surgery, and to identify predictors of differences between cardiac output measured by thermodilution and transthoracic electrical bioimpedance methods. DESIGN: Prospective repeated-measures study. SETTING: University-affiliated tertiary care center. PATIENTS: Thirty-four adult patients undergoing elective cardiac surgery with routine pulmonary artery catheter placement. INTERVENTIONS: Simultaneous paired cardiac output measurements by transthoracic electrical bioimpedance and thermodilution were made at four time points: within 2 hrs of intensive care unit (ICU) admission; when the patient reached a normothermic temperature; after extubation; and 24 hrs after ICU admission. MEASUREMENTS AND MAIN RESULTS: Mean measurements by each method over time did not differ, except at ICU admission, when compared by repeated-measures analysis of variance. For each time point, bias and precision between methods were calculated. Bias calculations ranged from 0.02 to 0.21 L/min/m2. Precision calculations ranged from 1.06 to 1.52 L/min/m2. Predictors of between-method differences identified by a multiple regression model of hemodynamic variables were: increased systemic vascular resistance index, decreased mean arterial pressure (MAP), and the presence of atrial or ventricular pacing. CONCLUSIONS: While mean postoperative cardiac output measurements did not differ by method over time, agreement between transthoracic electrical bioimpedance and thermodilution methods was poor in the immediate postoperative period, with precision calculations indicative of clinically significant differences. Increased systemic vascular resistance index and decreased MAP were predictive of larger between-method differences.

Aged↗
PubMed1995

Early psychosocial risks for adolescent suicidal ideation and attempts.

OBJECTIVE: An ongoing, 14-year, longitudinal community study examined psychosocial risks for adolescent suicidal ideation and attempts, as well as the link between earlier suicidal behavior and later functioning. METHOD: Nearly 400 youths were followed between the ages of 5 and 18 years. Suicidal ideation was assessed at age 15 and lifetime suicide attempts were determined at age 18. Risk factors covered developmental periods from birth to age 15, and most were measured prospectively using multiple informants. Late-adolescent functioning (at age 18) was based on both self-reports and school records. RESULTS: For both genders, the early onset (by age 14) of psychiatric disorders significantly increased the risk for suicidal ideation at age 15 and suicide attempts by age 18. Early gender-specific risks for suicidal ideation included preschool behaviors that are counter to typical gender norms, such as aggressive behavior in females and dependence in males. Suicidal ideation at age 15 and suicide attempts were both associated with deficits in later adolescence (at age 18) in behavioral and social-emotional functioning. CONCLUSIONS: Suicidal ideation at age 15 was a marker of distress with long-term implications for later functioning. The early gender-specific risk factors for suicidal behavior identified in this study can aid in developing strategies for prevention and early intervention.

Adolescent↗