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Biomedical subjects

S Herman

Publications and source records attributed to S Herman.

At least 19 recordsLinked to original sources

Low dose methotrexate induces apoptosis with reactive oxygen species involvement in T lymphocytic cell lines to a greater extent than in monocytic lines.

BACKGROUND: The mechanism by which low dose methotrexate (MTX) exerts its anti-inflammatory and immunosuppressive effect in rheumatoid arthritis (RA) patients is still debated. Recently it has been related to the induction of apoptosis. OBJECTIVE: We investigated the degree of apoptotic induction by MTX in lymphocytic (Jurkat T, EL4 T, and Raji B) and monocytic cell lines (U937 and THP1) and its relation to reactive oxygen species (ROS) generation, as a possible mechanism underlying the apoptotic events. METHODS: All cell types were incubated with a range of MTX concentrations (0.001, 0.01, 0.1, 1, and 10 muM) for up to 24 h. Cytotoxicity was assessed by Trypan Blue exclusion and MTT test; cell size and granularity by forward and side scatters (FSC, SSC). Apoptosis was measured by Annexin V test and FDA polarization; and mitochondrial ROS generation by DHR123 probe and by NAC inhibition. RESULTS: MTX significantly reduced cell viability and proliferation in all cell lines, being most effective in the Jurkat T lymphocytic line. The MTX cytotoxicity (at the optimal concentrations corresponding to low dose MTX therapy) was attributed to apoptosis, as suggested by morphological changes (shrinkage, increased granularity) and confirmed by Annexin V binding and FDA hyperpolarization. The apoptotic induction and the ROS generation (statistically correlated to apoptosis) were most pronounced in the Jurkat and EL4 T cell lines, and were partially inhibited by the antioxidant N-acetyl L-cysteine (NAC). CONCLUSION: According to the present observations, MTX may most likely induce apoptosis through oxidative stress. The high susceptibility of T cell lines to MTX induced apoptosis may account for the beneficial effect of MTX treatment in rheumatoid arthritis, which is characterized by hyperproliferation of T cells.

Acetylcysteine↗

Influence of contact hip stress on the outcome of surgical treatment of hips affected by avascular necrosis.

INTRODUCTION: Biomechanical analysis is an important tool that could improve the treatment of a diseased hip. However, it is still unclear how the biomechanical status affects the clinical outcome of a certain disease. In this work we studied the long-term effect of contact hip stress on the clinical outcome of hips that were operated on by various intertrochanteric osteotomies due to avascular necrosis of the femoral head. The hypothesis being tested is that the hips with a more favourable postoperative distribution of contact hip stress have a better clinical outcome. MATERIALS AND METHODS: The study was performed on a population of 30 hips. For each hip, we determined the peak contact hip stress before the operation and immediately after the operation by using a recently developed method based on a three-dimensional mathematical model and the data from standard anteroposterior roentgenographs of both hips and pelvis. The hips were evaluated clinically 9-26 years after the operation and divided into a successful and an unsuccessful group. The average change of the peak stress due to the operation was calculated for each group, and the values were compared by t-test. RESULTS: In the successful group the operation caused an average decrease of the peak hip stress of about 10%, while in the unsuccessful group the operation caused an average increase of the peak hip stress of about 4%, the difference between the respective changes of the peak stress due to the operation being statistically significant ( p=0.001). CONCLUSION: Our results support the hypothesis that the hips with a more favourable postoperative distribution of contact hip stress have a better clinical outcome.

Adult↗

Hip stress reduction after Chiari osteotomy.

A mathematical model was developed to study the effect of the Chiari osteotomy on the distribution of contact hip stress over the weight-bearing area. It was shown that Chiari osteotomy can increase the weight-bearing area directly (on the lateral side), owing to the additional area formed by the ala ossis ilii segment, and indirectly (on the medial side), owing to the shift of the stress pole in the medial direction. As a consequence, the contact hip stress is reduced after Chiari osteotomy. The indirect effect is important and often larger than the direct one. Using the proposed mathematical model and standard anteroposterior roentgenographs from archives, the average peak stress on the weight-bearing area, normalised with respect to the body weight (pmax/ W(B)), was determined before and after Chiari osteotomy (8,310m(-2) and 4,480 m(-2), respectively) on a population of 29 dysplastic hips. The difference was statistically significant (p < 0.005). Based on the results presented, it can be concluded that the hip joint contact stress in dysplastic hips considerably decreases after Chiari osteotomy, indicating a favourable biomechanical effect of this operation.

Hip Dislocation↗

Using stable isotopes to assess the bioavailability of minerals in food fortification programs.

The fortification of various types of food with minerals is often undertaken without consideration of either their bioavailability or the potential nutrient-nutrient interactions resulting from their use. Stable isotopes provide a safe and accessible method of resolving these issues by providing the proper evidence in each case. They must be conducted according to strict safety and ethical guidelines and may be readily conducted in a field setting. Clinical studies in children enable researchers, policymakers, and food manufacturers to obtain the data necessary to determine the best way to fortify specific foods and beverages, in order to optimally enhance the nutritional health of growing children. We have shown the utility of this approach in studies in both developing countries and in the United States.

Biological Availability↗

Srchi24, a chitinase homolog lacking an essential glutamic acid residue for hydrolytic activity, is induced during nodule development on Sesbania rostrata.

The interaction between the tropical legume Sesbania rostrata and the bacterium Azorhizobium caulinodans results in the formation of nodules on both stem and roots. Stem nodulation was used as a model system to isolate early markers by differential display. One of them, Srchi24 is a novel early nodulin whose transcript level increased already 4 h after inoculation. This enhancement depended on Nod factor-producing bacteria. Srchi24 transcript levels were induced also by exogenous cytokinins. In situ hybridization and immunolocalization experiments showed that Srchi24 transcripts and proteins were present in the outermost cortical cell layers of the developing nodules. Sequence analyses revealed that Srchi24 is similar to class III chitinases, but lacks an important catalytic glutamate residue. A fusion between a maltose-binding protein and Srchi24 had no detectable hydrolytic activity. A function in nodulation is proposed for the Srchi24 protein.

Amino Acid Sequence↗

Estimating the prevalence of anaemia: a comparison of three methods.

OBJECTIVE: To determine the most effective method for analysing haemoglobin concentrations in large surveys in remote areas, and to compare two methods (indirect cyanmethaemoglobin and HemoCue) with the conventional method (direct cyanmethaemoglobin). METHODS: Samples of venous and capillary blood from 121 mothers in Indonesia were compared using all three methods. FINDINGS: When the indirect cyanmethaemoglobin method was used the prevalence of anaemia was 31-38%. When the direct cyanmethaemoglobin or HemoCue method was used the prevalence was 14-18%. Indirect measurement of cyanmethaemoglobin had the highest coefficient of variation and the largest standard deviation of the difference between the first and second assessment of the same blood sample (10-12 g/l indirect measurement vs 4 g/l direct measurement). In comparison with direct cyanmethaemoglobin measurement of venous blood, HemoCue had the highest sensitivity (82.4%) and specificity (94.2%) when used for venous blood. CONCLUSIONS: Where field conditions and local resources allow it, haemoglobin concentration should be assessed with the direct cyanmethaemoglobin method, the gold standard. However, the HemoCue method can be used for surveys involving different laboratories or which are conducted in relatively remote areas. In very hot and humid climates, HemoCue microcuvettes should be discarded if not used within a few days of opening the container containing the cuvettes.

Anemia↗

Heterotopic bone formation in total hip arthroplasty: predisposing factors, classification and the significance for clinical outcome.

PURPOSE OF THE STUDY: Heterotopic bone formation in the area around the femoral head is a recognised complication following total hip arthroplasty. The aim of the study was to determine the prevalence of heterotopic ossification and to select a method of classification. Also, we studied the potential association of heterotopic bone with the following variables: sex, age at operation, operative technique, type of prosthesis and previous surgery on the ipsilateral hip. MATERIAL: The study involved 103 consecutive patients who underwent total hip replacement at our department in 1995. 175 patients were excluded from the study. Among 103 patients there were 35 male and 68 female patients. METHOD: Antero-posterior radiographs of the hips were reviewed preoperatively, six weeks after the operation and at one year after surgery. The degree of heterotopic bone formation was determined using the classifications of Brooker et al. (Grades 0-IV) and Kjaersgaard-Andersen et al. (Grades I and II). RESULTS: Heterotopic bone has developed in 27 (26.2%) patients, in 37% of male patients, mean age 59.8 years, and in only 20.5% female patients mean age 68.3 years. Brooker et al. Grade I ossification developed in 37% of the patients, Grade II in 44.4% and Grade III in 18.6%. According to the Kjaersgaard-Andersen et al. classification 22 patients developed Grade I and 5 patients Grade II ossification. The leading indication for surgery was osteoarthrosis, followed by aseptic necrosis (7.4%). Heterotopic bone formation was found in 20% of all patients with aseptic necrosis of the femoral head. Only 2.7% of patients operated on the ipsilateral hip developed ossifications. DISCUSSION: The study has shown that the incidence of ossifications is relatively low, yet still within the range of percentages reported in the literature. The finding that heterotopic bone most frequently develops in men and women older than 65 years both with osteoarthrosis is consistent with some authors. We found no association between the incidence of heterotopic ossification and the operative approach used or the type of prosthesis implanted, which has been confirmed by other investigators. Authors confirm that clinical parameters were significantly affected only in the most severe cases of ossification. CONCLUSION: The study has identified male patients and female patients older than 65 years both with osteoarthrosis as risk factors for the formation of heterotopic bone. The prevalence did not depend on the operative approach or type of prosthesis used. Heterotopic ossification was not associated with previous operative treatment of the hip. Both classification systems used in this study have proved reliable.

Aged↗

Anti-angiogenic cues from vascular basement membrane collagen.

Vascular basement membrane is an important structural component of blood vessels and has been shown to interact with and modulate vascular endothelial behavior during angiogenesis. During the inductive phase of tumor angiogenesis, this membrane undergoes many degradative and structural changes and reorganizes to a native state around newly formed capillaries in the resolution phase. Such matrix changes are potentially associated with molecular modifications that include expression of matrix gene products coupled with conformational changes, which expose cryptic protein modules for interaction with the vascular endothelium. We speculate that these interactions provide important endogenous angiogenic and anti-angiogenic cues. In this report, we identify an important antiangiogenic vascular basement membrane-associated protein, the 26-kDa NC1 domain of the alpha1 chain of type IV collagen, termed arresten. Arresten was isolated from human placenta and produced as a recombinant molecule in Escherichia coli and 293 embryonic kidney cells. We demonstrate that arresten functions as an anti-angiogenic molecule by inhibiting endothelial cell proliferation, migration, tube formation, and Matrigel neovascularization. Arresten inhibits the growth of two human xenograft tumors in nude mice and the development of tumor metastases. Additionally, we show that the anti-angiogenic activity of arresten is potentially mediated via mechanisms involving cell surface proteoglycans and the alpha1beta1 integrin on endothelial cells. Collectively, our results suggest that arresten is a potent inhibitor of angiogenesis with a potential for therapeutic use.

Animals↗

Fat intake and breast cancer risk in an area where fat intake is low: a case-control study in Indonesia.

BACKGROUND: Associations of fat and other macronutrients with breast cancer risk are not clear in areas where fat intake is low. METHODS: We conducted a hospital-based case-control study from 1992 to 1995 in Jakarta, Indonesia. RESULTS: The study, based on 226 cases and 452 age and socioeconomic status matched controls, provided the following findings. (a) In the pre-marriage period, the greater the fat or protein consumption, the larger the risk, whereas decreasing risk with increasing carbohydrate intake was detected. The odds ratio (OR) for the highest quartile of intake relative to the lowest was 8.47 (95% CI: 4.03-17.8) for fat, 2.19 (95% CI: 1.30-3.69) for protein, and 0.16 (95% CI: 0.08-0.31) for carbohydrate. A positive association with fat and a negative one with carbohydrate were also observed for the post-marriage period, but of weaker magnitude compared to the pre-marriage period. (b) The effects of macronutrient intakes were stronger among premenopausal than among postmenopausal women. (c) Most of the associations of protein and carbohydrate were insignificant after adjustment for fat intake. CONCLUSIONS: These findings suggest that fat intake might be an important determinant of breast cancer among populations with a low fat diet in Indonesia.

Adult↗

Stability of plasma human immunodeficiency virus load in VACUTAINER PPT plasma preparation tubes during overnight shipment.

VACUTAINER PPT plasma preparation tubes were evaluated to determine the effects of various handling and shipping conditions on plasma human immunodeficiency virus (HIV) load determinations. Plasmas obtained from PPT tubes stored and shipped under nine different conditions were compared to conventional EDTA tube plasmas stored at -70 degrees C within 2 h after phlebotomy. Compared to viral loads in frozen EDTA plasma, those in PPT tube plasma that was frozen immediately and either separated or shipped in situ were not significantly different. Viral loads in PPT tube plasma after storage for 6 h at either room temperature or 4 degrees C, followed by shipment at ambient temperature or on wet or dry ice, were not significantly different from baseline viral loads in EDTA or PPT plasma. The results of this study indicate that the HIV load in PPT tube plasma is equivalent to that in standard EDTA plasma. Plasma viral load is not affected by storage or shipment temperature when plasma is collected in PPT tubes. Furthermore, plasmas can be shipped in spun PPT tubes, and the tubes provide a safer and more convenient method for sample collection and transport than regular EDTA tubes.

Anticoagulants↗

Comparison of two amplification technologies for detection and quantitation of human immunodeficiency virus type 1 RNA in the female genital tract. Division of AIDS Treatment Research Initiative 009 Study Team.

Human immunodeficiency virus type 1 (HIV-1) RNA levels in female genital tract and peripheral blood samples were compared using two commercial amplification technologies: the Roche AMPLICOR HIV-1 MONITOR test and either the Organon Teknika nucleic acid sequence-based amplification (NASBA-QT) assay or the NucliSens assay. Estimates of HIV-1 RNA copy number were derived from internal kit standards and analyzed unadjusted and adjusted to a common set of external standards. We found a discordance rate of approximately 18% between the two technologies for the detection of HIV-1 in either the genital tract or peripheral blood samples. Detection discordance was not consistent among specimens or among women. There were no significant differences in adjusted or unadjusted estimates of HIV-1 RNA copy number in the genital tract samples using the AMPLICOR HIV-1 MONITOR test and either the NASBA-QT assay or the NucliSens assay. In addition, the estimated HIV-1 RNA copy number in peripheral blood samples did not differ when tested with the NucliSens assay and the AMPLICOR HIV-1 MONITOR test using kit standards. However, there was a significant difference in estimated RNA copy number between the NASBA-QT assay and the AMPLICOR HIV-1 MONITOR test for internal kit standards, which, as we have previously shown, was eliminated after adjustment with the external standards. Our results suggest that the Roche and Organon Teknika assays are equivalent for quantifying HIV-1 RNA in female genital tract specimens, although variation in detection does exist.

Cross-Sectional Studies↗

Extensive metallosis and necrosis in failed prostheses with cemented titanium-alloy stems and ceramic heads.

We describe three prostheses with cemented titanium-alloy stems and Al2O3 ceramic femoral heads which had to be revised after a mean period of implantation of 78 months. In each case, the neck of the prosthesis had been so severely worn that the profile was elliptical rather than circular. There was severe metallosis of the periprosthetic tissues. Metal particles isolated from the tissues were approximately one nanometre in size and the ratios of titanium, aluminium and vanadium in the particles were the same as in the original alloy. Histologically, the high concentration of metal particles masked the presence of high-density polyethylene (HDP) debris, but again particles about one nanometre in size were isolated from the tissues. The severe necrobiosis and necrosis noted were consistent with other reports of the presence of extensive wear particles in periprosthetic tissues. Wear is presumed to have occurred as a result of mismatch between the shape or size of the taper cone and the femoral head, or to changes in the geometry of loading due to migration of the cup. To facilitate early intervention, patients with this design of prosthesis should be monitored radiologically.

Aged↗

Effects of exercise training on older patients with major depression.

BACKGROUND: Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated. OBJECTIVE: To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial. METHODS: One hundred fifty-six men and women with MDD (age, > or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. RESULTS: After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving combination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms. CONCLUSIONS: An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD.

Aged↗

Assay of plasma samples representing different HIV-1 genetic subtypes: an evaluation of new versions of the amplicor HIV-1 monitor assay.

Quantification of plasma HIV-1 RNA levels has rapidly become the main tool for monitoring disease progression and treatment. However, some first-generation assays do not accurately quantify all HIV-1 subtypes. This study compares the first-generation and two newer prototype Amplicor HIV-1 Monitor assays (Roche Diagnostic Systems) in terms of their performance in quantifying HIV-1 RNA in stored plasma samples from 101 individuals infected with various genetic subtypes of HIV-1 (28 subtype A, 18 B, 26 C, 20 D, 2 E, 3 G, 2 H, and 2 J). The HIV-1 subtype had previously been determined by direct sequencing of the V3 domain of the env gene. The results from the three assays agreed for subtypes B and C, as well as for most subtype D samples. In contrast, the first-generation assay reported significantly lower plasma HIV-1 RNA levels than did the two newer versions of the assay for most subtype A, E, G, and H samples. There were no differences in mean plasma HIV-1 RNA levels between individuals infected with subtypes A, B, C, and D if the results from the two newer test versions were used, and if an adjustment was made between subtypes for differences in CD4 count. Thus, this study confirms that the first-generation assay does not accurately quantify HIV-1 RNA levels in many individuals infected with subtype A, E, G, and H. These problems appeared to have been greatly reduced in the two new prototype versions.

Evaluation Studies as Topic↗

Chalcone reductase-homologous transcripts accumulate during development of stem-borne nodules on the tropical legume Sesbania rostrata.

During a search for genes with induced or enhanced expression in the early stages of development of stem-borne nodules on Sesbania rostrata, a cDNA with homology to chalcone reductase (CHR) genes was isolated. Here, we describe the characterization of a full-length CHR cDNA (Srchr1) and the pattern of CHR transcript accumulation in stem-borne nodules. Expression was correlated with both nodule development and bacterial invasion. In young nodules, CHR transcripts were observed in cells of the parenchyma, in cells around the nodule vascular bundles, and in the uninfected cells of the central tissue.

Alcohol Oxidoreductases↗

Analysis of postdischarge change in a dual diagnosis population.

Many individuals with serious mental illnesses have co-occurring drug and alcohol problems. The research reported in this article examined an integrated inpatient mental illness-chemical dependency program and compared it with standard inpatient psychiatric treatment for two groups: those demonstrating high change from baseline to two-months postdischarge and those with negative or no change. Univariate analyses revealed significant differences in the change groups on baseline personal-clinical characteristics and on aspects of their social and physical environments. The results have implications for improving mental health practice by better predicting patients who will optimally benefit from inpatient treatment.

Adult↗