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Biomedical subjects

J Freund

Publications and source records attributed to J Freund.

At least 37 records · Page 2Linked to original sources
PubMed1998

A splice variant of trkB and brain-derived neurotrophic factor are co-expressed in retinal pigmented epithelial cells and promote differentiated characteristics.

There is evidence suggesting reciprocal trophic interactions between photoreceptors and the retinal pigmented epithelium (RPE), but the factors involved have not been identified. In this study, we investigated the hypothesis that one or more known neurotrophic factors act upon the RPE. Cultured human and freshly isolated bovine RPE cells demonstrated saturable specific binding for [125I]labeled BDNF, NT-4/5 and NT-3 with little specific binding for CNTF and none for NGF. Cross-competition experiments showed that BDNF is the preferred ligand and cross-linking of [125I]BDNF resulted in a doublet at 160 kd that was increased in RPE cells incubated in all-trans retinoic acid. There was basal phosphorylation of a 145 kd protein recognized by an anti-trk antibody that was increased in RPE cells pulsed with BDNF. RT-PCR with primers spanning the transmembrane domain demonstrated that RPE cells express trkB mRNA lacking a region homologous to exon 9 of chicken trkB, a splice variant that has been demonstrated to preferentially interact with BDNF. Northern blots demonstrated that cultured RPE cells also express mRNA for BDNF. BDNF did not stimulate proliferation or increase survival of RPE cells in serum-free medium, but promoted a differentiated morphology and increased the expression of cellular retinaldehyde binding protein, a marker of the differentiated state in RPE cells. An RPE cell line that spontaneously shows differentiated features showed a high level of BDNF mRNA. These data demonstrate that RPE cells express a short splice variant of trkB whose activation correlates with expression of differentiated characteristics and the cells themselves are capable of producing a ligand for the receptors. Signaling through trkB could play a role in differentiation of RPE cells during development and maintenance of the differentiated state in adult RPE.

Animals↗
PubMed1998

Prediction of 10 repetition maximum for short-arc quadriceps exercise from hand-held dynamometer and anthropometric measurements.

Short-arc quadriceps exercise are commonly prescribed in physical therapy for strengthening knee extensor musculature. Determining the appropriate starting resistance has traditionally been a trial-and-error procedure. Therefore, developing an expedient method of estimating the correct starting resistance may lead to a more accurate exercise prescription. The primary purpose of this study was to establish a technique for predicting an individual's 10 repetition maximum (10 RM) based on hand-held dynamometer (HHD) strength recording and additional anthropometric predictor variables. Fifty healthy subjects (31 males and 19 females), aged 22-53 years, participated in the study. A prediction equation for determining 10 RM using HHD strength recording, weight, gender, and age was developed. By implementing this equation, clinicians can predict a normal, healthy, young to middle-aged adult's 10 RM within +/- 4.17 kg with a 95% confidence level (SEE = 2.13 kg).

Adult↗
PubMed1998

Cerebral perfusion scanning in treating AIDS dementia: a pilot study.

UNLABELLED: Acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) is a common effect of the AIDS virus. We studied the regional cerebral blood flow of patients with early ADC and its response to atevirdine mesylate. METHODS: Ten men with early ADC, who had failed or were intolerant to zidovudine or didanosine therapy, were treated with atevirdine mesylate for 12 wk. Cerebral perfusion SPECT using 99mTc-HMPAO was performed at Week 0 and Week 12. SPECT images were analyzed qualitatively and semiquantitatively. RESULTS: The cerebral perfusion abnormalities in early ADC were usually mild and characteristically involved the cortices and periventricular regions bilaterally and symmetrically. Four patients were able to complete the protocol. Three of these patients responded to atevirdine clinically, two of whom showed improvement in their Week 12 SPECT images. The other responder had an essentially unchanged image. The patient who did not respond to atevirdine showed a definite deterioration in cerebral perfusion. CONCLUSION: Cerebral perfusion SPECT is useful in detecting and assessing therapeutic responses in ADC. The preliminary results of atevirdine in treating ADC are promising and need further investigation.

AIDS Dementia Complex↗
PubMed1997

Neurotrophic factors, cytokines and stress increase expression of basic fibroblast growth factor in retinal pigmented epithelial cells.

Basic fibroblast growth factor (bFGF) and FGF receptors have been localized to photoreceptors and retinal pigmented epithelium (RPE), but the function of bFGF in adult retina and RPE is unknown. Exogenous bFGF has a neuroprotective effect in retina and brain and its expression is increased in some neurons in response to cytokines or stress. In this study, we investigated the effect of light, other types of stress, neurotrophic factors, and cytokines on bFGF levels in cultured human RPE. Some agents that protect photoreceptors from the damaging effects of constant light, including brainderived neurotrophic factor (BDNF), ciliary neurotrophic factor, and interleukin-1 beta, increase bFGF mRNA levels in RPE cells. Intense light and exposure to oxidizing agents also increase bFGF mRNA levels in RPE cells and cycloheximide blocks the increase. An increase in bFGF protein levels was demonstrated by ELISA in RPE cell supernatants after incubation with BDNF or exposure to intense light or oxidizing agents. These data indicate that bFGF is modulated in RPE cells by stress and by agents that provide protection from stress and support the hypothesis that bFGF functions as a survival factor in the outer retina.

Blotting, Northern↗
PubMed1997

A comparison of longitudinal measurements in the spine and proximal femur using lunar and hologic instruments.

Absolute values of bone mineral density (BMD), using dual-energy X-ray absorptiometry (DXA), differ between instruments from different manufacturers. Despite these differences, the rates of change calculated from serial measurements on different densitometers have been assumed to be comparable. We compared the change in BMD in 34 subjects in the lumbar spine and at the standard sites in the proximal femur, from measurements performed using a Lunar DPX-L and a Hologic QDR-1000. Measurements were obtained on the same day, and repeated on the same day, on both machines after a mean interval of 4.8 years (range 4.1-6.3 years). There were strong positive correlations between the percentage change in BMD calculated using the two machines in the lumbar spine, trochanteric region, and total proximal femur: r = 0.82, 0.84, and 0.73, respectively (p < 0.0001 at all sites). In the femoral neck and in Ward's triangle, the correlations were not as high: r = 0.55 (p = 0.003) and 0.43 (p = 0.028), respectively. At all sites, despite the significant correlations, the agreement between the two densitometers was not high and there may be significant errors in individual subjects if one uses measurements from one densitometer to predict the change in BMD using the scanner of the other manufacturer. There is less of a problem comparing group data in the lumbar spine and trochanteric region, although errors are still likely to occur in comparing group data of bone loss, calculated using different densitometers, in the other proximal femur sites. In conclusion, the study suggests that caution is necessary in combining bone loss data derived using densitometers from different manufacturers, particularly in the proximal femur. This has important implications for multicenter studies.

Absorptiometry, Photon↗
PubMed1996

Screening for osteoporosis: what is the role of heel ultrasound?

Could focused population screening detect osteoporosis earlier and improve the management of this major health care problem? Quantitative ultrasound of the calcaneus is currently being proposed as a suitable screening technique. Correlations between quantitative ultrasound of the calcaneus and dual energy x-ray absorptiometry of bone mineral density of the spine and proximal femur are not high enough to reliably predict bone mineral density at the lumbar spine or proximal femur from the ultrasound results. Some ongoing longitudinal studies suggest that quantitative ultrasound may none the less detect individuals at increased risk of fracture, but its use for mass screening for osteoporosis would be premature.

Absorptiometry, Photon↗
PubMed1996

Pilot study of the efficacy of atevirdine in the treatment of AIDS dementia complex.

OBJECTIVES: To determine the efficacy of the non-nucleoside reverse transcriptase inhibitor atevirdine in the treatment of AIDS dementia complex (ADC). DESIGN: Open label pilot study. METHODS: Ten patients with ADC (stage 1 or 2) who were intolerant to zidovudine or dideoxyinosine, or in whom the antiretrovirals had failed to prevent further decline in CD4 cell levels, were entered into the study. Atevirdine, 1800 mg daily in three divided doses, was given over a 12-week period. Patients were assessed neurologically and neuropsychologically every 4 weeks. Cerebrospinal fluid analysis was performed at entry and at weeks 4 and 12. Technetium-99 exametazine single photon emission computed tomographic cerebral perfusion scans and magnetic resonance imaging brain scans were performed at weeks 0 and 12. RESULTS: Five patients completed the 12 week protocol. Four of these five responded to atevirdine, as judged by quantified neurological and neuropsychological assessments. Atevirdine was well tolerated apart from the development of rash, anxiety, intermittent diarrhoea and fatigue. CONCLUSIONS: These preliminary results suggest that atevirdine is efficacious in the treatment of ADC. Larger blinded studies of this class of drug in the treatment of ADC are required.

AIDS Dementia Complex↗
PubMed1996

Bile acid malabsorption in HIV infected patients with chronic diarrhoea.

AIMS: To look for the presence of bile acid malabsorption in HIV infected patients with chronic diarrhoea and determine whether bile sequestering agents may have a role in palliating this common problem. METHODS: Nineteen HIV infected patients with chronic diarrhoea (duration > one month) poorly controlled on conventional treatment were investigated using the seven day retention of 75seleno-23-homocholic acid taurine (SeHCAT) as a measure of bile acid loss from the enterohepatic circulation. Patients with evidence of bile acid malabsorption were offered cholestyramine. RESULTS: Sixteen (84%) had evidence of bile acid malabsorption (< 15% retention at seven days). Ten of the 16 patients with bile acid malabsorption had terminal ileal biopsies-six had ileitis and four normal histology, suggesting that malabsorption is not always related to terminal ileitis. Thirteen patients with bile acid malabsorption have been treated with cholestyramine and 11 have reported a symptomatic response. CONCLUSIONS: Bile acid malabsorption can be demonstrated in some cases of HIV associated chronic diarrhoea and we suggest a therapeutic trial of a bile sequestering agent in patients whose symptoms are not well controlled using conventional anti-diarrhoeal agents.

Adult↗
PubMed1996

Specific cleavage sites of Nef proteins from human immunodeficiency virus types 1 and 2 for the viral proteases.

Human immunodeficiency virus type 2 (HIV-2) Nef is proteolytically cleaved by the HIV-2-encoded protease. The proteolysis is not influenced by the absence or presence of the N-terminal myristoylation. The main cleavage site is located between residues 39 and 40, suggesting a protease recognition sequence, GGEY-SQFQ. As observed previously for Nef protein from HIV-1, a large, stable core domain with an apparent molecular mass of 30 kDa is produced by the proteolytic activity. Cleavage of Nef from HIV-1 in two domains by its own protease or the protease from HIV-2 is also independent of Nef myristoylation. However, processing of HIV-1 Nef by the HIV-2 protease is less selective than that by the HIV-1 protease: the obtained core fragment is heterogeneous at its N terminus and has an additional cleavage site between amino acids 99 and 100. Preliminary experiments suggest that the full-length Nef of HIV-2 and the core domain are part of the HIV-2 particles, analogous to the situation reported recently for HIV-1.

Aspartic Acid Endopeptidases↗
PubMed1996

Abdominal fat and insulin resistance in normal and overweight women: Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM.

Insulin resistance appears to be central to obesity, NIDDM, hyperlipidemia, and cardiovascular disease. While obese women with abdominal (android) fat distribution are more insulin resistant than those with peripheral (gynecoid) obesity, in nonobese women, the relationship between abdominal fat and insulin resistance is unknown. By measuring regional adiposity with dual-energy X-ray absorptiometry and insulin sensitivity by euglycemic-hyperinsulinemic clamp in 22 healthy women, with a mean +/- SE body BMI of 26.7 +/- 0.9 kg/m2 and differing risk factors for NIDDM, we found a strong negative relationship between central abdominal (intra-abdominal plus abdominal subcutaneous) fat and whole-body insulin sensitivity (r = -0.89, P < 0.0001) and nonoxidative glucose disposal (r = -0.77, P < 0.001), independent of total adiposity, family history of NIDDM, and past gestational diabetes. There was a large variation in insulin sensitivity, with a similar variation in central fat, even in those whose BMI was <25 kg/m2. Abdominal fat had a significantly stronger relationship with insulin sensitivity than peripheral nonabdominal fat (r2 = 0.79 vs. 0.44), and higher levels were associated with increased fasting nonesterified fatty acids, lipid oxidation, and hepatic glucose output. Because 79% of the variance in insulin sensitivity in this heterogeneous population was accounted for by central fat, abdominal adiposity appears to be a strong marker and may be a major determinant of insulin resistance in women.

Abdomen↗
PubMed1995

Complete 1H nuclear magnetic resonance assignments and structural characterization of a fusion protein of the alpha-amylase inhibitor tendamistat with the activation domain of the human immunodeficiency virus type 1 Tat protein.

Complete sequence-specific assignments of the 1H-NMR spectrum of a fusion protein of the alpha-amylase inhibitor tendamistat from Streptomyces tendae and the activation domain of Tat from human immunodeficiency virus type 1 (HIV-1) was obtained by homonuclear two-dimensional NMR methods. The protein behaves as expected for an ideal fusion protein: the flexible linker allows an almost completely decoupled motion of the subunits of the protein and the two subunits show almost no mutual interaction. In the tendamistat part, small structural distortions due to exchange of the carboxy-terminal leucine propagate mainly via the hydrogen bonds of the beta-sheet and the disulfide bond. The Tat part of the protein contains the seven cysteine residues of full-length Tat. The fusion protein was expressed in Streptomyces lividans and exported. During the export to the extracellular space disulfide bonds are created by the expressing cells, only one sulfhydryl group remains accessible for sulfhydryl reagents. Although a unique, dominant conformation with a specific disulfide bonding pattern exists, a significant conformational variation can be observed including cis-proline peptide bonds, which may indicate smaller populations with alternative disulfide bonding patterns.

Amino Acid Sequence↗
PubMed1995

Adults with growth hormone deficiency have abnormal body composition but normal energy metabolism.

We compared body composition and energy metabolism in a cross-sectional study involving 21 GH-deficient (GHD) and 29 normal adults. Fifteen subjects from each group were pair-matched for age, sex, height, and weight. Comparison of body composition by dual energy x-ray absorptiometry in the 15 pairs showed that GHD subjects had a significantly greater fat mass (23.9 +/- 1.8 vs. 19.8 +/- 2.6 kg; P = 0.02), lower bone mineral content (2.6 +/- 0.1 vs. 2.9 +/- 0.1 kg; P = 0.06), and lower fat-free soft tissue mass (FFSTM; 45.8 +/- 2.5 vs. 48.9 +/- 2.6 kg; P = 0.02). To determine which subcompartment changes were responsible for the reduced FFSTM in GH deficiency, extracellular water (ECW) was measured by 24Na dilution in 11 of the subject pairs, and body cell mass (BCM) was derived by subtracting ECW from FFSTM. The GHD subjects had lower ECW (19.4 +/- 1.0 vs. 21.0 +/- 1.0 kg; P = 0.05) and BCM (26.6 +/- 1.9 vs. 28.6 +/- 2.1 kg; P = 0.08) than their normal counterparts, with the difference approaching statistical significance. When the relationship between ECW and FFSTM was compared in the larger group of 18 GHD and 27 normal subjects, no statistically significant difference was found between the 2 regression lines, indicating that ECW and BCM were proportionately reduced in GH deficiency. Energy expenditure and fuel utilization before and after a standardized mixed meal were measured by indirect calorimetry in 12 matched pairs of GHD and normal subjects. Comparison of energy expenditure and fuel utilization showed no significant difference in fasting or postprandial energy expenditure, or carbohydrate or fat oxidation rates between the two groups. We conclude that GHD adults have an increased FM, a reduced FFSTM due to a proportionate reduction in ECW and BCM, and no detectable disturbance in energy metabolism.

Adult↗