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Biomedical subjects

I Janssen

Publications and source records attributed to I Janssen.

At least 37 records · Page 2Linked to original sources

Isolation and characterization of adult microglial cells and oligodendrocytes derived from postmortem human brain tissue.

The present study provides a detailed description of the simultaneous establishment and immunocytochemical characterization of highly enriched human adult microglial cell cultures as well as of oligodendrocyte cultures. For this study, brain tissue specimens were collected at autopsy with relatively short postmortem times (3-9 h) from various regions of the CNS of Alzheimer's disease, Pick's disease and non-demented control cases. Although methods to isolate viable glial cells from human adult brain tissue have been described, these human brain specimens were often derived from surgical resections, i.e., in order to treat intractable epilepsy, brain tumors or cardiovascular diseases involving the brain. However, for the study of many neurological disorders, surgical material is not available. Furthermore, for obvious reasons, there is a limit to the number of central nervous system (CNS) regions from which (enough) tissue can be obtained at surgery. The adherent primary microglial cells, isolated according to the here described procedures consisted of proliferating, phagocytotic cells that expressed various microglia/macrophage-specific markers as judged by immunocytochemical analysis. Non-adherent cells isolated from the same brain tissue samples expressed oligodendrocyte-specific markers. The current described culture system may provide a valuable tool in studying human CNS biology and disease.

Aged↗

Three words three shapes: A clinical test of memory.

Three Words - Three Shapes was designed as an easy "bedside" test for elderly patients that assesses verbal and nonverbal memory within the same modality. In the present study, it was administered to patients with probable Alzheimer's disease (PRAD), a control group of non-demented older subjects (NC) and a group of patients with Korsakoff's amnesia (KA). Incidental recall and several other measures of learning, retention and recognition differentiated control from PRAD and KA subjects. PRAD and KA subjects' performance was similar, but there were some material-specific interactions. This test is relatively easy and some of the derived measures could prove useful in staging amnesia progression beyond the earliest stages of PRAD when more difficult tests yield floor effects.

Aged↗

Total-body skeletal muscle mass: development and cross-validation of anthropometric prediction models.

BACKGROUND: Skeletal muscle (SM) is a large body compartment of biological importance, but it remains difficult to quantify SM with affordable and practical methods that can be applied in clinical and field settings. OBJECTIVE: The objective of this study was to develop and cross-validate anthropometric SM mass prediction models in healthy adults. DESIGN: SM mass, measured by using whole-body multislice magnetic resonance imaging, was set as the dependent variable in prediction models. Independent variables were organized into 2 separate formulas. One formula included mainly limb circumferences and skinfold thicknesses [model 1: height (in m) and skinfold-corrected upperarm, thigh, and calf girths (CAG, CTG, and CCG, respectively; in cm)]. The other formula included mainly body weight (in kg) and height (model 2). The models were developed and cross-validated in nonobese adults [body mass index (in kg/m(2)) < 30]. RESULTS: Two SM (in kg) models for nonobese subjects (n = 244) were developed as follows: SM = Ht x (0.00744 x CAG(2) + 0.00088 x CTG(2) + 0.00441 x CCG(2)) + 2.4 x sex - 0.048 x age + race + 7.8, where R:(2) = 0.91, P: < 0.0001, and SEE = 2.2 kg; sex = 0 for female and 1 for male, race = -2.0 for Asian, 1.1 for African American, and 0 for white and Hispanic, and SM = 0.244 x BW + 7.80 x Ht + 6.6 x sex - 0.098 x age + race - 3.3, where R:(2) = 0.86, P: < 0.0001, and SEE = 2.8 kg; sex = 0 for female and 1 for male, race = -1.2 for Asian, 1.4 for African American, and 0 for white and Hispanic. CONCLUSION: These 2 anthropometric prediction models, the first developed in vivo by using state-of-the-art body-composition methods, are likely to prove useful in clinical evaluations and field studies of SM mass in nonobese adults.

Adult↗

ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group.

BACKGROUND: Inhibition of the renin-angiotensin system is known to raise serum potassium [K(+)] levels in patients with renal insufficiency or diabetes. No study has evaluated the comparative effects of an angiotensin-converting enzyme (ACE) inhibitor versus an angiotensin receptor blocker (ARB) on the changes in serum [K(+)] in people with renal insufficiency. METHODS: The study was a multicenter, randomized, double crossover design, with each period lasting one month. A total of 35 people (21 males and 14 females, 19 African Americans and 16 Caucasian) participated, with the mean age being 56 +/- 2 years. Mean baseline serum [K(+)] was 4.4 +/- 0.1 mEq/L. The glomerular filtration rate (GFR) was 65 +/- 5 mL/min/1.73 m(2), and blood pressure was 150 +/- 2/88 +/- 1 mm Hg. The main outcome measure was the difference from baseline in the level of serum [K+], plasma aldosterone, and GFR following the initial and crossover periods. RESULTS: For the total group, serum [K(+)] changes were not significantly different between the lisinopril or valsartan treatments. The subgroup with GFR values of < or = 60 mL/min/1.73 m(2) who received lisinopril demonstrated significant increases in serum [K(+)] of 0.28 mEq/L above the mean baseline of 4.6 mEq/L (P = 0.04). This increase in serum [K(+)] was also accompanied by a decrease in plasma aldosterone (P = 0.003). Relative to the total group, the change in serum [K(+)] from baseline to post-treatment in the lisinopril group was higher among those with GFR values of < or = 60 mL/min/1.73 m(2). The lower GFR group taking valsartan, however, demonstrated a smaller rise in serum [K(+)], 0.12 mEq/L above baseline (P = 0.1), a 43% lower value when compared with the change in those who received lisinopril. This blunted rise in [K(+)] in people taking valsartan was not associated with a significant decrease in plasma aldosterone (P = 0.14). CONCLUSIONS: In the presence of renal insufficiency, the ARB valsartan did not raise serum [K(+)] to the same degree as the ACE inhibitor lisinopril. This differential effect on serum [K(+)] is related to a relatively smaller reduction in plasma aldosterone by the ARB and is not related to changes in GFR. This study provides evidence that increases in serum [K(+)] are less likely with ARB therapy compared with ACE inhibitor therapy in people with renal insufficiency.

Aldosterone↗

Obesity reduction through lifestyle modification.

Obesity is a worldwide public health problem. One in three Canadians is overweight, a prevalence that is already high and increasing. Moreover, 54% of men and 37% of Canadian women are characterized as abdominally obese, the phenotype that is strongly associated with cardiovascular disease and type II diabetes. These observations underscore the importance of considering the efficacy of methods commonly used to reduce total and abdominal obesity. These strategies include a decrease in energy intake (diet), an increase in energy expenditure (exercise), or pharmacological intervention. The combination of diet and exercise is more commonly prescribed, with pharmacological intervention suggested only when lifestyle changes fail to achieve weight loss. The aim of this report is to review current knowledge regarding the influence of diet and exercise as treatment strategies for obesity reduction and provide recommendations for attaining and maintaining a healthy weight. The importance of diet composition in the treatment of obesity is also considered.

Abdomen↗

Plasma leptin in moderately obese men: independent effects of weight loss and aerobic exercise.

The independent effects of weight loss and exercise on plasma leptin and total (AT), subcutaneous (SAT), and visceral (VAT) adipose tissue were investigated in 52 obese men. Subjects were randomly assigned to four 12-wk protocols: 1) control (C, n = 8), 2) diet-induced weight loss (DWL, n = 14), 3) exercise-induced weight loss (EWL, n = 14), and 4) exercise with weight maintenance (EWS, n = 16). Plasma leptin was unchanged in C (from 7.8 +/- 1.3 to 7.7 +/- 1.0 ng/ml). Equivalent weight loss (7.5 kg) decreased leptin significantly but similarly (DWL, from 8.5 +/- 1.0 to 4.8 +/- 0.6 ng/ml; EWL, from 10.1 +/- 1.0 to 5.0 +/- 0.6 ng/ml). Exercise in the absence of weight loss did not alter leptin levels (from 10.1 +/- 1. 3 to 9.2 +/- 1.2 ng/ml). Changes in leptin correlated with changes in AT and SAT (both P < 0.05) but not in VAT. We conclude that reduction in adipose tissue after weight loss results in a collateral decrease in circulating leptin, and exercise, independent of its effects on weight loss, has no profound influence on leptin secretion.

Adipose Tissue↗

Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr.

We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogeneous sample of 468 men and women. Men had significantly (P < 0.001) more SM in comparison to women in both absolute terms (33.0 vs. 21.0 kg) and relative to body mass (38.4 vs. 30.6%). The gender differences were greater in the upper (40%) than lower (33%) body (P < 0.01). We observed a reduction in relative SM mass starting in the third decade; however, a noticeable decrease in absolute SM mass was not observed until the end of the fifth decade. This decrease was primarily attributed to a decrease in lower body SM. Weight and height explained approximately 50% of the variance in SM mass in men and women. Although a linear relationship existed between SM and height, the relationship between SM and body weight was curvilinear because the contribution of SM to weight gain decreased with increasing body weight. These findings indicate that men have more SM than women and that these gender differences are greater in the upper body. Independent of gender, aging is associated with a decrease in SM mass that is explained, in large measure, by a decrease in lower body SM occurring after the fifth decade.

Adolescent↗

Estimation of skeletal muscle mass by bioelectrical impedance analysis.

The purpose of this study was to develop and cross-validate predictive equations for estimating skeletal muscle (SM) mass using bioelectrical impedance analysis (BIA). Whole body SM mass, determined by magnetic resonance imaging, was compared with BIA measurements in a multiethnic sample of 388 men and women, aged 18-86 yr, at two different laboratories. Within each laboratory, equations for predicting SM mass from BIA measurements were derived using the data of the Caucasian subjects. These equations were then applied to the Caucasian subjects from the other laboratory to cross-validate the BIA method. Because the equations cross-validated (i.e., were not different), the data from both laboratories were pooled to generate the final regression equation SM mass (kg) = [(Ht 2 / R x 0.401) + (gender x 3.825) + (age x -0. 071)] + 5.102 where Ht is height in centimeters; R is BIA resistance in ohms; for gender, men = 1 and women = 0; and age is in years. The r(2) and SE of estimate of the regression equation were 0.86 and 2.7 kg (9%), respectively. The Caucasian-derived equation was applicable to Hispanics and African-Americans, but it underestimated SM mass in Asians. These results suggest that the BIA equation provides valid estimates of SM mass in healthy adults varying in age and adiposity.

Adolescent↗

Exercise alone is an effective strategy for reducing obesity and related comorbidities.

The commonly held view that exercise alone is not a useful strategy for obesity reduction is drawn from studies with limitations that confound interpretation. Recent evidence counters the dogma that daily exercise produces only modest weight loss and suggests that exercise without diet restriction is an effective strategy for reducing obesity and related co-morbidities.

Adipose Tissue↗

Synthesis and biological evaluation of selected insect neuropeptide analogs modified by D- or L-phenylglycine derivatives.

Novel analogs, modified by L- or D- phenylglycine and p-substituted derivatives, of the neuromodulator proctolin (Arg-Tyr-Leu-Pro-Thr) and of the Trypsin Modulating Oostatic Factor from the gray flesh fly Neobellieria bullata (Neb-TMOF-Asn-Pro-Thr-Asn-Leu-His) were synthesized and checked for activity. Proctolin analogs were modified at position 2: Arg-Phg-Leu-Pro-Thr (I), Arg-D-Phg-Leu-Pro-Thr (II), Arg-Phg(p-OH)-Leu-Pro-Thr (III), Arg-D-Phg(p-OH)-Leu-Pro-Thr (IV), Arg-Phg(p-NO2)-Leu-Pro-Thr (V) Arg-D-Phg(p-NO2)-Leu-Pro-Thr (VI), Arg-Phg(p-NH2)-Leu-Pro-Thr (VII), Arg-D-Phg(p-NH2)-Leu-Pro-Thr (VIII), Arg-Phg(p-N,N-di-Me)-Leu-Pro-Thr (IX), Arg-D-Phg(pp-N,N-di-Me)-Leu-Pro-Thr (X) while analogs of Neb-TMOF underwent modifications at position 6: Asn-Pro-Thr-Asn-Leu-Phg(p-NO2) (XI), Asn-Pro-Thr-Asn-Leu-D-Phg(p-NO2) (XII), Asn-Pro-Thr-Asn-Leu-Phg(p-NH2) (XIII), Asn-Pro-Thr-Asn-Leu-D-Phg(p-NH2) (XIV), Asn-Pro-Thr-Asn-Leu-Phg(p-N,N-di-Me) (XV), Asn-Pro-Thr-Asn-Leu-D-Phg(p-N,N-di-Me) (XVI). Earlier studies on proctolin demonstrated that the presence of the -CH2- group between C-alpha and the phenyl ring at position 2 of the peptide chain is important for the myotropic activity. Based on these results, we replaced Tyr at position 2 by different phenylglycine derivatives, lacking the methylene group at the side chain. Myotropic activity of the proctolin analogs was assayed in vitro on the semi-isolated heart of the mealworm Tenebrio molitor and on the foregut of the locust Schistocerca gregaria. All analogs (I-X) were practically inactive. For Neb-TMOF, it was previously demonstrated that the exchange of His-6 by p-substituted Phe-derivatives, especially by Phe(p-NH2), an amino acid containing a basic function, results into analogs which inhibit trypsin biosynthesis in the gray fleshfly. For this reason these new Neb-TMOF analogs with L- or D-phenylglycine p-substituted derivatives at position 6, were developed and tested (in vivo) in the trypsin biosynthesis assay of the gray fleshfly N. bullata. Only analogs XV and XVI slightly inhibited trypsin biosynthesis in the midgut. Because more than 50% of the injected animals died and none of the surviving animals ate much of the liver meal, the lower trypsin level in the gut might be a indirect effect. Other peptides (XI-XIV) had no effect on the level of trypsin biosynthesis in the midgut.

Animals↗

Cytokines associated with amyloid plaques in Alzheimer's disease brain stimulate human glial and neuronal cell cultures to secrete early complement proteins, but not C1-inhibitor.

Complement activation products C1q, C4c/d, and C3c/d in amyloid plaques in Alzheimer's disease probably result from direct binding and activation of C1 by amyloid beta peptides. RT-PCR and in situ hybridization studies have shown that several complement factors are produced in the brain parenchyma. In the present study, cytokines that can be detected in amyloid plaques (i.e., interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha) were found to differentially stimulate the expression of C1 subcomponents, C1-Inhibitor (C1-Inh), C4, and C3, by astrocyte and microglial cell cultures derived from postmortem adult, human brain specimens and by neuroblastoma cell lines in culture. C1r and C1s were secreted at low levels by astrocytes and neuroblastoma cell lines. Exposure of cells to IL-1 alpha, IL-1 beta, TNF-alpha and to a far lesser extent IL-6, markedly upregulated C1r, C1s, and C3 production. C4 synthesis increased in response to interferon (IFN)-gamma and IL-6, whereas that of C1-Inh could be stimulated only by IFN-gamma. Thus, C1-Inh production is refractory to stimulation by plaque-associated cytokines, whereas these cytokines do stimulate C1r, C1s, and also C4 and C3 secretion by astrocytes and neuronal cells in culture. In contrast to the amyloid plaque associated cytokines IL-1 beta, IL-1 alpha, and TNF-alpha, the amyloid peptide A beta 1-42 itself did not stimulate C1r and C1s synthesis by astrocytes, microglial cells, or neuroblastoma cell lines. Microglial cells were the only cell type that constitutively expressed C1q. The ability of C1q to reassociate with newly formed C1r and C1s upon activation of C1 and subsequent inactivation by C1-Inh, may enable ongoing complement activation at sites of amyloid deposition, especially when C1-Inh is consumed and not replaced.

Aged↗

Ring chromosomes in a malignant mesenchymoma.

We report, for the first time, the cytogenetic and molecular genetic constitution of a human mesenchymoma. As in several other soft tissue sarcomas, supernumerary ring and rod-shaped marker chromosomes were observed next to an otherwise normal diploid karyotype. Comparative genomic in situ hybridization and whole chromosome painting experiments revealed that chromosome 1q21-q25 and 12q14-q15 sequences were amplified, and that these sequences resided on the supernumerary marker chromosomes. We assume that, in this malignant mesenchymoma, the observed chromosomal anomalies may be associated with its well differentiated liposarcomatous component.

Buttocks↗

Effects of sex on the change in visceral, subcutaneous adipose tissue and skeletal muscle in response to weight loss.

OBJECTIVE: To examine the influence of sex on whole body and regional subcutaneous, visceral, total adipose tissue (AT), skeletal muscle (SM), and lean tissue in response to weight loss induced by diet alone (DO) or the combination of diet and aerobic (DA) or resistance exercise (DR). DESIGN: Sixty upper-body obese men and women were randomly assigned to one of three treatments: DO, DA, or DR. All tissues were measured using a whole body, magnetic resonance imaging protocol. RESULTS: Within each group reductions were observed for body weight ( approximately 11 kg), subcutaneous and visceral AT (P<0.01). After controlling for pretreatment differences in tissue size, reductions in total adiposity, total and regional subcutaneous and visceral adipose tissue were not different between sexes (P>0.1). Independent of sex, the reduction in visceral AT was greater than subcutaneous AT (P<0.05) in response to DO and DA. With the exception of DA women, the reduction in abdominal subcutaneous AT was greater (P<0.05) than lower-body subcutaneous AT in response to diet and exercise, but not diet alone, in both sexes (P>0.05). Independent of sex, skeletal muscle mass was preserved within the exercise groups (P>0.05) but not diet alone (P<0.05). Peak VO2 (l/min) improved in the DA groups as did muscular strength in the DR groups (P<0.01). CONCLUSIONS: These findings indicate that in response to diet or diet and exercise-induced weight loss, reductions in total adiposity, subcutaneous and visceral adipose tissue distribution are not different in obese men and women. Independent of sex, the combination of diet and exercise results in a preservation of skeletal muscle mass, a preferential reduction of abdominal subcutaneous AT, and improved functional capacity by comparison to diet alone.

Adipose Tissue↗

Is abdominal fat preferentially reduced in response to exercise-induced weight loss?

PURPOSE: It is known that a preferential deposition of fat in the abdominal region is the obesity phenotype that conveys the greatest health risk. Although physical activity is commonly prescribed to reduce obesity, the influence of exercise-induced weight loss on abdominal fat is unclear. This review was undertaken to clarify whether abdominal fat is preferentially reduced consequent to weight loss induced by regular exercise. METHODS: A literature search (Medline, 1966-1998) was performed using appropriate keywords to identify studies reporting changes in both whole body and abdominal fat in response to exercise. RESULTS: At present there are no randomized controlled trails (RCT) wherein it was clear that exercise alone induced weight loss. For the four RCT within which regular exercise was not associated with weight loss, abdominal fat measured by waist circumference was unchanged. A similar trend is observed for the nonrandomized studies. Abdominal obesity as measured by waist circumference is unchanged for those studies reporting no loss in weight or fat; however, a modest reduction (approximately 3 cm) is observed in response to exercise-induced weight loss of about 3 kg. Without exception, these studies were not designed to determine whether abdominal obesity was preferentially reduced. Absent from the literature are RCT that employ imaging techniques (e.g., computerized tomography or magnetic resonance imaging) to determine whether exercise-induced weight loss is associated with reductions in either visceral or abdominal subcutaneous fat. However, the findings from four nonrandomized or controlled studies report that exercise with or without weight loss is associated with reductions in both visceral and subcutaneous fat. CONCLUSION: There is insufficient evidence to determine whether exercise-induced weight loss is associated with reductions in abdominal fat. Clearly there is a need for carefully controlled studies wherein the primary aim is to determine the influence of regular exercise on total and abdominal adiposity.

Abdomen↗

Effects of aerobic or resistance exercise and/or diet on glucose tolerance and plasma insulin levels in obese men.

OBJECTIVE: This study had two objectives. First, we examined whether the influence of diet combined with either aerobic (DA) (n = 10) or resistance (DR) (n = 10) exercise has effects on insulin and glucose levels that are different in obese men. Second, we tried to determine whether the combination of diet and exercise is associated with improvements in insulin and glucose levels that are greater than those associated with diet alone (DO) (n = 9). RESEARCH DESIGN AND METHODS: Insulin and glucose levels were measured after an overnight fast and a 75-g oral glucose challenge (OGTT). Visceral adipose tissue (AT), subcutaneous AT, and skeletal muscle were measured by magnetic resonance imaging (MRI) before and after treatment (16 weeks). RESULTS: Reductions in weight (12.4 +/- 3.8 kg) and in visceral (37 +/- 15.1%) and subcutaneous AT (24.3 +/- 8.6%) were not different between treatments (P > 0.05). Skeletal muscle was maintained in the DA and DR groups but was reduced (7.3 +/- 2.8%) in the DO group (P < 0.05). Independent of treatment, fasting glucose and OGTT glucose did not change (P > 0.05). However, fasting insulin, OGTT insulin, and the insulin-to-glucose ratio decreased within all treatments (P < 0.05). Reductions in the OGTT insulin area under the curve were greater (P < 0.05) within the DA (52 +/- 12%) and DR (42 +/- 17%) treatments than in the DO (20 +/- 15%) treatment. Collapsed across group, reductions in visceral AT were related to reductions in fasting and OGTT glucose (P < 0.05), whereas reductions in abdominal subcutaneous AT correlated with reductions in fasting insulin (P < 0.05). CONCLUSIONS: Weight loss induced by diet and aerobic or resistance exercise has similar positive effects on lowering fasting and OGTT insulin values that are greater than those with diet alone. Because changes in glucose and insulin were related to reductions in visceral and abdominal subcutaneous AT, we conclude that reduction in abdominal obesity consequent to diet and exercise-induced weight loss is important for attaining improvements in plasma insulin levels, observations that strengthen the concept that abdominal obesity has an important role in mediating insulin resistance.

Adipose Tissue↗

Masked t(X;18)(p11;q11) in a biphasic synovial sarcoma revealed by FISH and RT-PCR.

The initial cytogenetic analysis of a biphasic synovial sarcoma showed an apparently normal karyotype. After FISH using chromosome X- and 18-specific probes and RT-PCR using SYT- and SSX-specific primer sets, a cryptic synovial sarcoma-associated t(X;18)(p11;q11) could be revealed. The "masked" nature of the translocation may best be explained by a two-step scenario in which a genuine t(X;18)(p11;q11) has occurred as a first step and a reverse reciprocal X;18 translocation as a second step, leaving the synovial sarcoma-associated SYT-SSX1 fusion intact. The findings further underline our previous suggestion that SYT-SSX1 fusions may correlate with a biphasic nature of the tumor. In addition, our findings indicate that, in analogy to, e.g., the Philadelphia translocation in chronic myeloid leukemia, "masked" translocations may occur in soft tissue tumors and that, as a standard, RT-PCR and/or FISH analyses should be carried out in order to provide karyotypic information that may be relevant to tumor diagnosis and/or prognosis.

Adult↗