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PubMed1984

Expression of macrophage functions in hybrids of a myeloma cell line with inflammatory macrophages: evidence for negative control mechanisms in the expression of macrophage functions.

Mouse inflammatory macrophages from C57BL/6N mice were fused with BALB/c mouse-derived myeloma cells (the CANS series). The hybrids in the early period after cell fusion (8 weeks) showed no macrophage functions (chemotaxis, EA and EAC rosette-forming abilities, phagocytosis or lysozyme production). EA rosette-forming ability was observed when these hybrids were treated with trypsin, whereas other macrophage functions were not. After prolonged culture, the hybrids (12 clones of 13 randomly selected) showed all the macrophage functions along with chromosome loss. Myeloma cell functions (kappa light chain production) were found in the young hybrids soon after cell fusion but were absent in the aged hybrids. These results indicated that reexpression of macrophage properties, except for EA rosette-forming abilities, takes place after the loss of chromosomes or genes repressing the expression of macrophage functions.

Animals↗

PubMed1994

Defective proliferation and regulatory function of CD4+ T cells bearing Leu-8 homing receptor in primary biliary cirrhosis. Phorbol myristate acetate enhances T-cell function.

The majority of circulating CD4+ T cells express the Leu-8 peripheral lymph node homing receptor, and these cells have previously been shown to have suppressor-inducer and suppressor function. In the present study, it was found that CD4+, Leu-8+ T cells from patients with primary biliary cirrhosis (PBC) have a significantly (P < 0.01) lower proliferative response when stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or pokeweed mitogen (PWM) compared to normal controls. The proliferative response of CD4+, Leu-8- T cells was similar in patients and controls. However, the proliferative responses of CD4+, Leu-8+ from patients with PBC was normal when cells were stimulated with PHA, Con A, anti-CD3 monoclonal antibody, or ionomycin in combination with phorbol myristate acetate (PMA). CD4+ T cells from patients with PBC mediated normal helper function for PWM-stimulated immunoglobulin synthesis at high T/B ratios and their regulatory function was similar to that of normal CD4+ T cells that had been irradiated to inactivate their suppressor activity. When CD4+ T cells from patients with PBC were precultured with the combination of Con A and PMA, they mediated potent inhibitory activity similar to that of normal CD4+ T cells. Thus, CD4+, Leu-8+ T cells from patients with PBC have a defect of proliferation and suppressor function that is reversed by coculture with PMA. This finding suggests that impairment of a PMA-inducible lymphocyte activation pathway contributes to abnormal lymphocyte function in PBC.

Adult↗

PubMed1988

Maternal speech to verbal and higher functioning versus nonverbal and lower functioning autistic children.

The relationship between autistic children's level of functioning and maternal speech to children was examined. Ten higher functioning verbal and 10 lower functioning nonverbal children were videotaped in a 15-minute interaction with their mothers. Results revealed that mothers of the higher functioning verbal children asked more questions, used more language modeling, gave more reinforcement for language, and answered more children-initiated questions than did mothers of the lower functioning nonverbal children. Mothers of the nonverbal children employed more directives, used shorter mean lengths of utterance, and reinforced their children's motoric rather than spoken behavior. Far from being poor models for linguistic behavior, mothers of autistic children appear, therefore, to be quite responsive to their children's relative capabilities.

Autistic Disorder↗

PubMed1994

The Bateman function revisited: a critical reevaluation of the quantitative expressions to characterize concentrations in the one compartment body model as a function of time with first-order invasion and first-order elimination.

The Bateman function, A"(e-k(e)t--e-k(a)t), quantifies the time course of a first-order invasion (rate constant ka) to, and a first-order elimination (rate constant ke) from, a one-compartment body model where A" = (gamma Dose)ka/(ka-ke)V. The rate constants (when ka > 3ke) are frequently determined by the "method of residuals" or "feathering." The rate constant ka is actually the sum of rate constants for the removal of drug from the invading compartment. "Flip-flop," the interchange of the values of the evaluated rate constants, occurs when ke > 3ka. Whether -ka or -ke is estimable from the terminal ln C-t slope can be determined from which apparent volume of distribution, V, derived from the Bateman function is the most reasonable. The Bateman function and "feathering" fail when the rate constants are equal. The time course is then expressed by C = gamma Dtk e-kt. The determination of such equal k values can be obtained by the nonlinear fitting of such C-t data with random error to the Bateman function. Also, rate constant equality can be concluded when 1/tmax and the kmin (value of ke at the minimum value of ek(e)tmax/ke plotted against variable ke values) are synonymous or when kmintmax approximates unity. Simpler methods exist to evaluate C-t data. When a drug has 100% bioavailability, regression of Dose/V/C on AUC/C in the nonabsorption phase gives ke no matter what is the ratio of m = ka/ke. Since k(e)tmax = ln m/(m-1), m can be determined from the given table relating m and k(e)tmax. When gamma is unknown, ke can be estimated from the abscissas of intersections of plots of Cmax ek(e)tmax and keAUC, both plotted vs. arbitrary values of ke, and gamma D/V values are estimable from the ordinate of the intersection. Also, when gamma is unknown, ke can be estimated from the abscissas of intersections (or of closest approaches) of ek(e)tmax/ke and AUC/Cmax, both plotted vs. arbitrary values of ke. The C-t plot of the Modified Bateman function, C = Be-lambda 2t-A e-lambda 1t, does not commence at the origin (i.e., when tc = 0 = 0 and when a lag time does not exist).(ABSTRACT TRUNCATED AT 400 WORDS)

Absorption↗

PubMed1996

Correlation between pancreatic endocrine and exocrine function and characteristics of pancreatic endocrine function in patients with diabetes mellitus owing to chronic pancreatitis.

CONCLUSION: Pancreatic endocrine capacities are remarkably disturbed in patients with pancreatic diabetes owing to calcific pancreatitis as opposed to those owing to noncalcific pancreatitis. Insulin secretion in calcific pancreatitis resembled that in insulin-dependent diabetes mellitus (IDDM), whereas insulin secretion in noncalcific pancreatitis resembled that in non-IDDM (NIDDM). The involvements of acinar cell and ductal cell function closely correlate with endocrine function (insulin and glucagon secretions) in chronic pancreatitis (pancreatic diabetes). BACKGROUND: We sought to clarify the differences of pancreatic endocrine function between pancreatic diabetes and primary diabetes, and to verify the correlations between pancreatic exocrine and endocrine dysfunction in patients with chronic pancreatitis. METHODS: Urinary C-peptide (CPR) excretion and fasting plasma glucagon levels in patients with pancreatic diabetes owing to calcific pancreatitis (19 cases) and owing to noncalcific pancreatitis (14 cases) were studied in comparison with those in patients with insulin-dependent diabetes mellitus (IDDM, 23 cases), noninsulin-dependent diabetes (NIDDM, 18 cases), and in healthy controls (11 cases). In addition, pancreatic exocrine function was investigated in patients with chronic pancreatitis (calcific and noncalcific) and in healthy controls. The correlation between pancreatic exocrine and endocrine function was studied. RESULTS: The urinary CPR excretion in controls was 94.9 +/- 20.5 micrograms/d. The urinary CPR excretion in calcific pancreatitis was 12.8 +/- 7.4 micrograms/d and it resembled that in IDDM (9.4 +/- 5.8 micrograms/d). The urinary CPR excretion in noncalcific pancreatitis was 41.5 +/- 30.1 micrograms/d, being similar to that in NIDDM (49.3 +/- 21.0 micrograms/d). The plasma glucagon level in calcific pancreatitis was 64.1 +/- 15.9 rho g/mL, which was significantly lower than the values in IDDM (111.2 +/- 50.2 rho g/mL) and NIDDM (96.7 +/- 21.9 rho g/mL). The plasma glucagon level in calcific and noncalcific pancreratitis (88.4 +/- 29.6 rho g/mL) were significantly lower than that in controls (129.8 +/- 21.6 rho g/mL). The residual capacities of acinar cells and ductal cells were strongly correlated with urinary CPR excretion and plasma glucagon concentration.

Adult↗

PubMed2006

Long-term persistence of both functional and non-functional alleles at the leukocyte immunoglobulin-like receptor A3 (LILRA3) locus suggests balancing selection.

The leukocyte immunoglobulin-like receptor (LILR) family consists of 13 loci, and a number of variations have been identified in these genes. Some polymorphisms of the LILR genes are reported to be associated with susceptibility to diseases such as rheumatoid arthritis and multiple sclerosis. LILRA3, one of the LILR genes, exhibits a presence or absence variation due to a 6.7-kb deletion in various populations. In this study, variation screening of the LILRA3 gene revealed high allele frequency of the 6.7-kb LILRA3 deletion (71%) in Japanese, in contrast to the frequency reported for the other populations. In addition, we identified a splice acceptor mutation in intron 1 with allele frequency of 19%, resulting in three alternatively spliced isoforms. Surprisingly, all of these isoforms were found to contain premature termination codons (PTCs) in the exon 3. Taken together, approximately 80% of Japanese lack functional LILRA3 alleles. The maximum likelihood coalescent analysis suggested that two major lineages, functional alleles and PTC-containing alleles, have been maintained for 2.75 million years in humans. These results prompted us to hypothesize that balancing selection had maintained both the functional and non-functional alleles at the LILRA3 locus. This hypothesis is consistent with the observation that the 6.7-kb LILRA3 deletion is detected worldwide in the presence of functional LILRA3 alleles.

Alleles↗

PubMedDate not supplied

Evaluation of optical function using a new point spread function analysis system in cataractous and pseudophakic eyes: preliminary results.

PURPOSE: To evaluate optical function in cataractous and pseudophakic eyes using the new point spread function (PSF) analysis system in a clinical setting. METHODS: We applied this new analysis system in the study of two cataractous eyes and one pseudophakic eye of two patients. Using a PSF analyzer, double-pass PSF was measured directly for each subject, and the single-pass modulation transfer function (MTF) and single-pass PSF were calculated. The simulated retinal images of various sizes of Landolt's rings and their contrast characteristics were also calculated by the PSF analyzer. RESULTS: The MTF and the contrast of the simulated retinal images degraded in cataractous eyes were compared with data for normal eyes; the degradation pattern depended on the opacification pattern. The MTF and the contrast of the simulated retinal images in the pseudophakic eye improved significantly compared with the cataractous eyes, although both values were lower in the pseudophakic eye than in young normal eyes. CONCLUSIONS: Our data showed degradation of optical function in cataractous and pseudophakic eyes in comparison with optical function in young normal eyes. If further accumulations of PSF data are made, it may be possible to establish an objective standard by which to measure the progression of cataract, as well as an objective indication for treatment in the future.

Aged↗

PubMed1985

Stepwise variable selection and maximum likelihood estimation of smoothing factors of kernel functions for nonparametric discriminant functions evaluated by different criteria.

Kernel functions are used to estimate the probability density functions of variables for nonparametric discriminant analysis. In connection with stepwise variable identification a stepwise maximum likelihood estimation procedure for the estimation of smoothing factors of the kernel functions is developed. This procedure allows a step-by-step estimation of smoothing factors for every variable which is considered to be added to the model or which is examined to substitute a variable in a model. Different criteria for model evaluation in stepwise discriminant analysis are discussed. Beside criteria, like distance and dependence functions and the error and nonerror rate, a criterion which considers the ratio of probability densities of different classes at point x is proposed for stepwise variable identification. An application of the procedures described in this study to a medical decision problem shows the importance of stepwise parameter estimation of kernel functions for nonparametric discriminant analysis and the role of different model evaluation criteria for the selection of the best subset of variables.

Biometry↗

PubMed1984

Functional index: a numerical expression of post-traumatic wrist function.

Accurate functional assessment is an essential part of the analysis of managing fractures. A new technique for the measurement of the wrist's function is described. Observations of a wrist's performance are made using three devices. A dynanometer records movement while acting against a resistive torque. Angular and rotational movement at the wrist is measured using a three-dimensional goniometer. A vigorometer is used to assess the strength of grip. The three derived measurements give a functional index for each patient. Eighty-nine patients sustaining fractures at the wrist were seen at the time of trauma and at an assessment clinic 6 months later. Statistical analysis has shown that all three measurements are necessary to assess function. A functional index has applications in clinical work and research.

Adolescent↗

PubMed1983

Glucose tolerance and B cell function in chronic alcoholism: its relation to hepatic histology and exocrine pancreatic function.

Glucose tolerance and B cell function were assessed in 30 consecutive chronic alcoholic patients without overt diabetes mellitus. Plasma glucose, insulin, and C peptide concentrations were measured during an oral glucose tolerance test. All patients underwent a liver biopsy and an exocrine pancreatic function test (Lundh test). Compared with the controls, the three groups of alcoholic patients (those with histologically normal livers, n = 12; those with steatosis, n = 10; and those with cirrhosis, n = 8) all had a two-fold increase in plasma concentrations of insulin as well as C peptide in the fasting state, despite normal fasting levels of glucose. After oral glucose all groups of patients had elevated plasma levels of glucose, insulin, and C peptide compared with the controls. The C peptide/insulin ratio was similar to that in the controls in all groups of alcoholics. Patients with decreased exocrine pancreatic function (n = 7) had a significantly lower insulin and C peptide response to glucose than the patients with normal exocrine pancreatic function. It is concluded that (1) chronic alcoholics even with histologically normal livers have endogenous insulin resistance, and (2) associated damage to the exocrine pancreas is more common than previously recognized and decompensation of B cell function could be demonstrated in patients with decreased exocrine pancreatic secretion.

Adolescent↗

PubMed1987

Effect of age, sex and health status on human lymphocyte functions: demonstration of a sex-related defect in suppressor cell function.

The mitogenic response of human lymphocytes and the short-lived suppressor cell function on concanavalin A response were studied as dependent variables in 194 patients using multiple regression analysis, with health status and sex as dummy variables, and age as an explicative one. This study confirms a decrease of the lymphocyte functional response to mitogens with aging. A sex-related defect in suppressor cell function is put forward in females independently of age. An inverse linear relationship is found between the functional response to pokeweed mitogen (T and B mitogen) and suppressor cell function in males but not in females. No such relationship is found with the pure T mitogens (Con A and phytohemagglutinin-A). The present study suggests that a defect in short-lived suppressor cells can play some role in the greater incidence and prevalence of autoimmune diseases in women while the depressed lymphocyte response of old people cannot be explained by modifications of the activity of these suppressor cells.

Adult↗

PubMed1989

Intrahemispheric sex differences in the functional representation of language and praxic functions in normal individuals.

Kimura (1980, The Behavioral and Brain Sciences, 3, 240-241; 1983, Canadian Journal of Psychology, 37, 19-35; 1987, Canadian Psychology, 28, 133-147) recently proposed that there are intrahemispheric sex differences in the organization of particular language and praxic functions such that in females these functions are more focally represented. This hypothesis, as well as supporting data, was derived from research with brain-injured subjects. The purpose of the present study was to test the utility of using dual-task methodology for investigating sex-related variation in intrahemispheric functional organization in normal individuals. Women were found to show greater interference than men on concurrent tasks of language and right-hand finger tapping. In support of Kimura's model, the present findings yielded evidence suggestive of intrahemispheric sex differences in the "functional distance" between language and praxic functions within the left hemisphere of normal individuals.

Adolescent↗

PubMed2005

Homocysteine versus the vitamins folate, B6, and B12 as predictors of cognitive function and decline in older high-functioning adults: MacArthur Studies of Successful Aging.

BACKGROUND: Elevated plasma total homocysteine concentration may be a risk factor for cognitive decline and Alzheimer disease, but data from prospective studies are limited. Further, high homocysteine levels are associated with low vitamin status, and it is unknown whether it is homocysteine toxicity or vitamin insufficiency that is responsible for the observed cognitive dysfunction. METHODS: We performed cross-sectional and longitudinal analyses of a cohort of 499 high-functioning community-dwelling persons aged 70 to 79 years to determine the effect of homocysteine and related vitamin plasma concentrations on cognitive function and cognitive decline. Nonfasting plasma concentrations of homocysteine, folate, vitamin B(6), and vitamin B(12) were measured at baseline. Summary measures of cognitive function were created from tests of multiple cognitive domains administered at baseline and again after 7 years. RESULTS: In cross-sectional analyses investigating each variable separately, subjects with elevated homocysteine levels, or low levels of folate or vitamin B(6), demonstrated worse baseline cognitive function. In longitudinal analyses, after adjusting for multiple covariates, including homocysteine, those in the bottom quartile of folate had a 1.6-fold increased risk (95% confidence interval: 1.01 to 2.31; P =0.04) of being in the worst quartile of 7-year cognitive decline. Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level. CONCLUSION: In high-functioning older adults, low folate levels appear to be a risk factor for cognitive decline. The risk of developing cognitive decline might be reduced through dietary folate intake.

Aged↗

PubMed2006

Left ventricular dysfunction in atrial fibrillation: restoration of sinus rhythm by the Cox-maze procedure significantly improves systolic function and functional status.

BACKGROUND: Atrial flutter or fibrillation with rapid, uncontrolled ventricular response may lead to left ventricular dysfunction, and conversion to sinus rhythm with control of heart rate can improve left ventricular ejection fraction. Little is known about the effects of the Cox-maze procedure on this form of tachycardia-induced cardiomyopathy. METHODS: Four hundred forty-three patients underwent the Cox-maze procedure from 1993 to 2002. Ninety-nine had atrial flutter or fibrillation without associated valvular or congenital heart disease, and 37 (37%) had decreased left ventricular function (ejection fraction < 0.35 in 11 [severe], ejection fraction 0.36 to 0.45 in 8 [moderate], and ejection fraction 0.46 to 0.55 in 18 [mild]). Ages of these 37 patients (34 male) ranged from 35 to 74 years (median, 55 years). RESULTS: Atrial flutter or fibrillation was present for 3 months to 19 years (median, 48 months) preoperatively, and 24 patients (65%) exhibited symptoms of heart failure. Preoperative ejection fraction ranged from 0.25 to 0.55 (median, 0.45). At last follow-up (median, 63 months), the Cox-maze procedure eliminated atrial flutter or fibrillation in all but 1 patient, and the greatest improvement was observed in patients with severe preoperative impairment (0.31 to 0.53; p = 0.01, preoperative versus follow-up), and patients with preoperative chronic atrial flutter or fibrillation (0.43 to 0.55; p < 0.05 preoperative versus follow-up). This improvement was observed immediately postoperatively and was sustained at last follow-up. Further, improvement in left ventricular function correlated with enhancement of functional status. CONCLUSIONS: In some patients, atrial flutter or fibrillation may be the cause rather than the consequence of left ventricular dysfunction. Importantly, systolic function and functional status can be significantly improved with the restoration of sinus rhythm by the Cox-maze procedure.

Adult↗

PubMed2005

Acceleration of functional reentry by rapid pacing in anisotropic cardiac monolayers: formation of multi-wave functional reentries.

OBJECTIVE: Attempts to cardiovert tachycardia by rapid point pacing can sometimes result in transient or stable increase of the heart rate (acceleration), changed ECG morphology, and/or fibrillation. The goal of this study was to investigate the effect of rapid pacing on the dynamics of functional reentry in monolayer cultures of cardiac cells. METHODS: Fully confluent, uniformly anisotropic monolayers of neonatal rat ventricular myocytes were prepared using methods of microabrasion. Cells were paced by a point electrode at rest and during functional reentry, and membrane voltages were optically mapped. RESULTS: Point pacing readily induced single loop anisotropic functional reentry with monomorphic optical pseudo-ECG (pECG) and average rotation period of 193+/-52 ms (n=71 monolayers). Attempts to cardiovert reentry by rapid pacing at rates 10-50% faster than the reentry rate were successful in 57/71 monolayers. In 14/71 monolayers, the number of rotating waves was stably increased by 1 to 4, yielding a 10-70% acceleration of pECG rate and change to a different monomorphic or polymorphic pECG. The resulting multi-wave functional reentries were classified based on the number and direction of their rotating waves. The higher the number of waves in the multi-wave reentry, the more accelerated was the rate of cell firing in the monolayer. Importantly, stable acceleration was only inducible in monolayers with relatively deep and broad conduction velocity restitution relationships. Reapplication of point pacing further accelerated, decelerated, or eventually terminated the reentrant activity. CONCLUSIONS: These results suggest that stable multiplication of rotating waves in conjunction with a deep and broad conduction velocity restitution relationship is a possible mechanism for stable acceleration of functional reentry by rapid pacing.

Animals↗

PubMed2004

Loss of an individual proteasome subunit alters motor function but not cognitive function or ambulation in mice.

The proteasome is a large intracellular protease, composed of multiple subunits, that is present in all cells. In the present study we examined motor function, cognitive function, and ambulation in transgenic mice that lack the low molecular protein 2 (LMP2) proteasome subunit. Comparison of LMP2 knock out (LMP2 KO) mice and non-transgenic mice of the same background demonstrate that LMP2 KO mice exhibit a higher degree of motor function, but possess a similar level of cognitive function and ambulation, as compared to non-transgenic control mice. Interestingly, LMP2 KO mice also exhibited increased body weight as compared to non-transgenic mice. These data demonstrate for the first time that specific proteasome subunits may play a role in regulating both brain function and body weight.

Animals↗

PubMed2005

Functional lipidomics: the roles of specialized lipids and lipid-protein interactions in modulating neuronal function.

Lipids fulfill multiple specialized roles in neuronal function. In brain, the conduction of electrical impulses, synaptic function, and complex signaling pathways depend on the temporally and spatially coordinated interactions of specialized lipids (e.g., arachidonic acid and plasmalogens), proteins (e.g., ion channels, phospholipases and cyclooxygenases) and integrative lipid-protein interactions. Recent technical advances in mass spectrometry have allowed unparalled insight into the roles of lipids in neuronal function. Through shotgun lipidomics and multidimensional mass spectrometry, in conjunction with the identification of new classes of phospholipases (e.g., calcium dependent and calcium independent intracellular phospholipases), new roles for lipids in cerebral function have been accrued. This review summarizes the advances in our understanding of the types of lipids and phospholipases in the brain and the role of functional lipidomics in increasing our chemical understanding of complex neuronal processes.

Animals↗

PubMed2005

The Social Occupational Functioning Scale (SOFS): a brief measure of functional status in persons with schizophrenia.

The social functioning of persons with schizophrenia contributes to their overall functional outcome and ability to live in the community. Enhancing the level of social functioning is an important treatment goal. The present study describes the development of the Social Occupational Functioning Scale (SOFS), a brief, yet comprehensive, easy to administer measure of social functioning for use in busy clinical settings. It has adequate psychometric properties in terms of reliability and validity. Exploratory factor analysis revealed a three-factor structure comprising of adaptive living skills, social appropriateness and interpersonal skills, accounting for 59% of the variance in total SOFS score.

Activities of Daily Living↗