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Biomedical subjects

N Ahmed

Publications and source records attributed to N Ahmed.

At least 19 recordsLinked to original sources
PubMed2001

Epitopes in the interacting regions of beta-dystroglycan (PPxY motif) and dystrophin (WW domain).

The dystroglycan gene produces two products from a single mRNA, the extracellular alpha-dystroglycan and the transmembrane beta-dystroglycan. The Duchenne muscular dystrophy protein, dystrophin, associates with the muscle membrane via beta-dystroglycan, the WW domain of dystrophin interacting with a PPxY motif in beta-dystroglycan. A panel of four monoclonal antibodies (MANDAG1-4) was produced using the last 16 amino acids of beta-dystroglycan as immunogen. The mAbs recognized a 43 kDa band on Western blots of all cells and tissues tested and stained the sarcolemma in immunohistochemistry of skeletal muscle over a wide range of animal species. A monoclonal antibody (mAb) against the WW domain of dystrophin, MANHINGE4A, produced using a 16-mer synthetic peptide, recognized dystrophin on Western blots and also stained the sarcolemma. We have identified the precise sequences recognized by the mAbs using a phage-displayed random 15-mer peptide library. A 7-amino-acid consensus sequence SPPPYVP involved in binding all four beta-dystroglycan mAbs was identified by sequencing 17 different peptides selected from the library. PPY were the most important residues for three mAbs, but PxxVP were essential residues for a fourth mAb, MANDAG2. By sequencing five different random peptides from the library, the epitope on dystrophin recognized by mAb MANHINGE4A was identified as PWxRA in the first beta-strand of the WW domain, with the W and R residues invariably present. A recent three-dimensional structure confirms that the two epitopes are adjacent in the dystrophin-dystroglycan complex, highlighting the question of how the two interacting motifs can also be accessible to antibodies during immunolocalization in situ.

Amino Acid Motifs↗
PubMed2001

The alphaVbeta6 integrin regulates its own expression with cell crowding: implications for tumour progression.

Expression of the growth-promoting integrin alphavbeta6 in colon cancer cells induces gelatinase B secretion and activation, the inhibition of which abolishes alphavbeta6-mediated tumour cell growth within a collagen matrix. Herein, we show that high cell density selectively enhances alphavbeta6 expression in a protein kinase C (PKC)-dependent manner in preference to other beta integrin subunits, resulting in a marked increase in gelatinase B secretion as cells reach confluence. Moreover, PKC activity increases with cell confluence, and the rise in PKC activity is much greater for alphavbeta6-expressing cells than for colon cancer cells which lack alphavbeta6. We propose a self-perpetuating system of colon cancer progression in which the integrin alphavbeta6 provides a means of sustaining tumour cell proliferation. In this model, alphavbeta6 regulates its own expression via a PKC-mediated signalling pathway as tumour cells become crowded and quiescent. The alphavbeta6-mediated induction of gelatinase B secretion facilitates peri-cellular matrix degradation, which helps overcome crowding and restores cell proliferation.

Antigens, Neoplasm↗
PubMed2001

Vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 serum level in patients with chest pain and normal coronary arteries (syndrome X).

BACKGROUND: Plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) mediators of leukocyte adhesion to vascular endothelium may implicate in the pathogenesis of the syndrome of chest pain with normal coronary arteries. HYPOTHESIS: We attempted to determine whether markers of endothelial activation are raised in patients with chest pain and normal coronary arteries. METHODS: We measured plasma VCAM-1, ICAM-1 (ng/ ml) in 36 patients (34 men, 2 women, aged 62 +/- 9 years) with stable angina, coronary artery disease (CAD), and a positive response to exercise test; in 21 patients (6 men, 15 women, aged 56 +/- 9 years) with chest pain and normal coronary arteriograms (syndrome X); and in 11 healthy control subjects (8 men, 3 women, aged 49 +/- 14 years). RESULTS: Plasma ICAM-1 levels were significantly higher both in patients with CAD (mean +/- standard error of the mean) (328 +/- 26, p < 0.05), and in syndrome X (362 +/- 22, p < 0.01) than in controls (225 +/- 29). VCAM-1 levels were also higher in syndrome X (656 +/- 42 ng/ml) and in patients with CAD (626 +/- 42 ng/ml) than in controls (551 +/- 60, p = 0.09). CONCLUSIONS: ICAM-1 and VCAM-1 levels are increased both in patients with CAD and with syndrome X compared with control individuals. These findings may suggest the presence of chronic inflammation with involvement of the endothelium in patients with anginal chest pain and normal coronary angiograms.

Adult↗
PubMed2001

Effect of bone morphogenetic protein-6 on haemopoietic stem cells and cytokine production in normal human bone marrow stroma.

Normal human bone marrow stroma cells include stem cells for both haemopoietic and osteochondrogenic lineages and express both bone morphogenetic protein (BMP) type I and type II receptors. As a member of the TGF-beta super-family, BMP-6 binds to both BMP type I and type II receptors and is involved in the developmental processes of renal and hepatic systems as well as of human foetal intestine. Also, BMP-6 induces osteoblastic differentiation of pluripotent mesenchymal cells and is an autocrine stimulator of chondrocyte differentiation. The present study was carried out to investigate the effect of BMP-6 on human cobblestone-area-forming cells (CAFC), that represent the functional primitive repopulating haemopoietic stem cell in long-term bone marrow culture. Also, the effect of BMP-6 on marrow stroma production of interleukin-6, -11 and their common receptor gp130 that is expressed in haemopoietic stem cells and is indispensable for their proliferation and tri-lineage differentiation was examined. Moreover, the effect of BMP-6 on marrow stroma release of soluble adhesion molecule VCAM-1 mediating the primitive haemopoietic stem cell adhesion to marrow stroma was examined. The number of CAFC was significantly reduced after BMP-6 treatment from 88+/-10 per 10(5)cells in control cultures in a dose dependent manner to only 48+/-3 per 10(5)cells in 50 ng/ml BMP-6-treated cultures, P< 0.01. Quantitative ELISA measurement revealed 50 ng/ml BMP-6 was able to significantly reduce IL-6 and IL-11 production from marrow stroma, P< 0.01. Also, BMP-6 significantly increased soluble gp130 release by 7.4-fold in 50 ng/ml BMP-6-treated marrow stroma cultures. The profound rapid increase in this natural antagonist of human IL-6 cytokine family may reduce the gp130 signaling. Also, the soluble VCAM-1 released increased by two-fold in 50 ng/ml BMP-6-treated marrow stroma cultures. The marked increase in the soluble form may exert an antagonist effect on the function of VCAM-1 (ligand for VLA4). Recently, blocking the VLA4/VCAM-1 adhesion pathway was shown to mobilise haemopoietic CD34 positive cells in normal individuals. Also, we previously observed a significantly lower expression of VLA4 (CD49d) on G-CSF-mobilised blood CD34 positive cells than on bone marrow CD34 positive cells before mobilisation in the same normal donors. Since BMP are currently being used in clinical trials for bone repair and fracture healing, the present results suggest a possible role for BMP-6 in mobilising CD34 positive cells for transplantation. Further in vitro tests are required to evaluate this potential mobilising role of BMP-6 in human long-term bone marrow culture.

Antigens, CD↗
PubMed2001

High initial blood pressure after acute stroke is associated with poor functional outcome.

OBJECTIVE: To evaluate the relationship between high initial blood pressure and functional outcome in patients with acute stroke. DESIGN: An observational study based on the data from the Intravenous Nimodipine West European Stroke Trial (INWEST). INWEST was a placebo-controlled randomized study terminated prematurely; subsequent analysis found a correlation between diastolic BP (DBP) reduction caused by high-dose nimodipine and unfavourable outcome. Subjects. Of the 295 patients with acute ischaemic stroke (within 24 h) recruited in the INWEST, 265 were included in this analysis [n = 92 for placebo, n = 93 for low-dose nimodipine (1-mg h(-1)) and n=80 for high-dose nimodipine (2-mg h(-1))]. Definition. Initial BP was defined as BP at the time of randomization. Normal initial BP (NIBP)=systolic BP (SBP) 120-160 and DBP 60-90 mmHg (n=126). Four alternatives were defined as high initial BP (HIBP): (1) >160/90 (n=126), (2) >170/95 (n=106), (3) >180/100 (n=63), (4) >190/105 (n=45). Main outcome measures. Combined death or dependency (DD) (Barthel index < 60) at 21 days. RESULTS: In multiple logistic regression analyses, the odds ratio [OR] for DD at day 21 was significantly higher in patients with any definition of HIBP than with NIBP. For all patients, OR and 95% confidence intervals [CI] for 160/90 versus NIBP=3.1, 1.3-7.3, respectively; for 170/95=3.3, 1.4-8.1; for 180/100=7.0, 2.1-22.8; for 190/105=3.7, 1.1-12.4. For only placebo patients, OR and 95% CI for 160/90=4.8, 1.2-19.3; for 170/95=4.4, 1.1-17.8; for 180/100=12.7, 2.2-74.7; for 190/105=5.6, 1.1-30.0. The outcome was similar at 24 weeks but did not reach statistical significance for the placebo patients. CONCLUSION: Patients with HIBP had a poor functional outcome after acute stroke.

Acute Disease↗
PubMed2001

Increased plasma adhesion molecule levels in patients with heart failure who have ischemic heart disease and dilated cardiomyopathy.

BACKGROUND: Inflammatory mechanisms, including leukocyte activation, appear to play a pathogenetic role in the development of heart failure. Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are important mediators of leukocyte adhesion to vascular endothelium. The plasma levels of the soluble form of these molecules may be elevated in chronic inflammation. METHODS AND RESULTS: We measured plasma VCAM-1 and ICAM-1 levels (in nanograms per milliliter) with the commercially available enzyme-linked immunosorbent assay method in 12 patients (9 male, 3 female, aged 64 +/- 8 years) with dilated cardiomyopathy and heart failure, in 23 patients (23 male, aged 65 +/- 9 years) with ischemic cardiomyopathy and heart failure, and in 11 healthy control subjects (8 male, 3 female, aged 49 +/- 14 years). Plasma ICAM-1 levels were higher both in patients with dilated cardiomyopathy (363 +/- 77 ng/mL, P <.05) (mean +/- SEM) and in those with ischemic heart disease (320 +/- 32 ng/mL, P <.05) than in control subjects (225 +/- 29 ng/mL). VCAM-1 levels were also higher in both groups with heart failure (664 +/- 73 ng/mL) than in control subjects (551 +/- 60 ng/mL). VCAM-1 levels were higher in patients with class IV compared with those with class II and III heart failure. CONCLUSIONS: Plasma adhesion molecule levels are increased in patients with heart failure and are unrelated to the presence or absence of angiographically demonstrable atherosclerotic coronary artery disease. The plasma level of VCAM-1 correlates with the severity of heart failure.

Aged↗
PubMed2001

Biosorption of copper by a bacterial biofilm on a flexible polyvinyl chloride conduit.

Inexpensive technologies with less-than-optimal efficiencies as a strategy for countering economic restraints to pollution control have been evaluated by using a laboratory-scale biotreatment process for copper-containing effluent. Economizing measures include the use of polyvinyl chloride (PVC) cylinders fashioned from commercially available flexible PVC conduit to support a biofilm that was cultured in an inexpensive medium prepared in wastewater. The biofilm was challenged by aqueous copper solution in a bioreactor and subsequently analyzed under a scanning electron microscope with energy-dispersive X-ray microanalysis.

Biofilms↗
PubMed2001

The skeletal metastatic complications of renal cell carcinoma.

Of the 103 patients with advanced renal cell carcinoma 31 (30%) developed symptomatic radiologically confirmed skeletal metastases. These were typically lytic, predominantly affecting the axial skeleton and associated with considerable skeletal morbidity. Solitary bone lesions occurred in 14 (45%) of patients. The median survival of patients with bone metastases was 12 months. Hypercalcaemia was common in patients both with (29%) and without (44%) bone metastases. The number and rate of skeletal related events was similar to that seen from bone metastases from breast cancer. It would therefore be appropriate to evaluate the effectiveness of bisphosphonate treatment for reducing skeletal morbidity in advanced renal cell cancer with bone metastases.

Adult↗
PubMed2001

An unusual presentation of thyroglossal duct cyst.

Thyroglossal duct cyst usually presents as a painless swelling in the mid-line of the neck. This is the first documented case of an acute presentation of hoarseness and multi-loculated swelling. It also contrasts the limitations of ultrasonography with the accuracy of magnetic resonance imaging in such atypical swellings.

Adult↗
PubMed2000

Chloride channel activity of ClC-2 is modified by the actin cytoskeleton.

The chloride channel ClC-2 has been implicated in essential physiological functions, including cell-volume regulation and fluid secretion by specific epithelial tissues. Although ClC-2 is known to be activated by hyperpolarization and hypo-osmotic shock, the molecular basis for the regulation of this channel remains unclear. Here we show in the Xenopus oocyte expression system that the chloride-channel activity of ClC-2 is enhanced after treatment with the actin-disrupting agents cytochalasin and latrunkulin. These findings suggest that the actin cytoskeleton normally exerts an inhibitory effect on ClC-2 activity. An inhibitory domain was previously defined in the N-terminus of ClC-2, so we sought to determine whether this domain might interact directly with actin in binding assays in vitro. We found that a glutathione S-transferase fusion protein containing the inhibitory domain was capable of binding actin in overlay and co-sedimentation assays. Further, the binding of actin to this relatively basic peptide (pI 8.4) might be mediated through electrostatic interactions because binding was inhibited at high concentrations of NaCl with a half-maximal decrease in signal at 180 mM NaCl. This work suggests that electrostatic interactions between the N-terminus of ClC-2 and the actin cytoskeleton might have a role in the regulation of this channel.

Actins↗
PubMed2000

B16 melanoma cell arrest in the mouse liver induces nitric oxide release and sinusoidal cytotoxicity: a natural hepatic defense against metastasis.

The formation of liver metastases involves interactions between intravascular cancer cells and the hepatic microvasculature. Here we provide evidence that the arrest of intravascular B16F1 melanoma cells in the liver induces a rapid local release of nitric oxide (NO) that causes apoptosis of the melanoma cells and inhibits their subsequent development into hepatic metastases. B16F1 melanoma cells (5 x 10(5)) labeled with fluorescent microspheres were injected into the portal circulation of C57BL/6 mice. The production of NO in vivo was detected by electron paramagnetic resonance spectroscopy ex vivo using an exogenous NO-trapping agent. A burst of NO was observed in liver samples examined immediately after tumor cell injection. The relative electron paramagnetic resonance signal intensity was 667 +/- 143 units in mice injected with tumor cells versus 28 +/- 5 units after saline injection (P < 0.001). Two-thirds of cells arrested in the sinusoids compared with the terminal portal venules (TPVs). By double labeling of B16F1 cells with fluorescent microspheres and a TdT-mediated UTP end labeling assay, we determined that the melanoma cells underwent apoptosis from 4-24 h after arrest. The mean rate of apoptosis was 2-fold greater in the sinusoids than in the TPVs at 4, 8, and 24 h after injection (P < 0.05-0.01). Apoptotic cells accounted for 15.9 +/- 0.8% of tumor cells located in the sinusoids and 7.1 +/- 0.9% of tumor cells in the TPVs. The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester completely blocked the NO burst (P < 0.001) and inhibited the apoptosis of B16F1 cells in the sinusoids by 77%. However, the rate of tumor cell apoptosis in the TPVs was not changed. There were 5-fold more metastatic nodules in the livers of N(G)-nitro-L-arginine methyl ester-treated mice (P < 0.05). The inactive enantiomer N(G)-nitro-D-arginine methyl ester had no effect on the initial NO burst or on apoptosis of tumor cells in vivo. Both annexin V phosphatidylserine plasma membrane labeling and DNA end labeling of apoptotic cells were demonstrated after a 5-min exposure (a time equivalent to the initial transient NO induction in vivo) of B16F1 cells to a NO donor in vitro. These results identify the existence of a natural defense mechanism against cancer metastasis whereby the arrest of tumor cells in the liver induces endogenous NO release, leading to sinusoidal tumor cell killing and reduced hepatic metastasis formation.

Animals↗
PubMed2000

DDRT-PCR: use of agarose gels for detection of amplified products.

The present study focuses on the detection of differentially expressed genes in migrating (healing) and nonmigrating (normal) corneal epithelium on agarose gel using a modified procedure of differential display reverse transcriptase-polymerase chain reaction (DDRT-PCR). Rabbit corneal epithelial organ cultures were used to obtain nonmigrating and migrating samples. RNA was extracted using Trizol LS reagent. PCR was modified in order to allow detection of amplified products on 3% agarose gel with ethidium bromide staining. Products were also resolved on 6% denaturing polyacrylamide-urea gels and observed by silver staining. Agarose gels showed two prominent bands that were heavily expressed in the 458 bp and 587 bp region of the nonmigrating samples. In addition light bands were visible in the region corresponding to 234 bp and 450 bp. In the migrating samples, two light bands were visible in the region of 267 bp and 300 bp. Eight amplicons, six in the nonmigrating corneal epithelial sample and two in the migrating corneal epithelial samples, were also found to be differentially expressed when products were run on 6% denaturing polyacrylamide-urea gels. Thus, DDRT-PCR products can be detected on agarose gels and prove very helpful and economical in the initial studies of DDRT-PCR.

Animals↗
PubMed2000

Retinoic acid suppresses interleukin 6 production in normal human osteoblasts.

Systemic long-term retinoid therapy for chronic skin diseases significantly reduced bone turnover markers within days and led to bone abnormalities. Retinoic acid (RA) plays a key role in the regulation of mouse bone cell proliferation, differentiation and functions. Meanwhile, there is little information of RA effect on human osteoblast and osteoclast cell development and function. Interleukin 6 (IL-6) is a pleiotropic cytokine with profound effects on bone metabolism. Thus, the present study examined the RA effect on cell differentiation, alkaline phosphatase and osteocalcin production as well as IL-6 production in normal human osteoblasts. The number of large differentiated osteoblast cells decreased in RA-treated cultures P<0.05. The production of bone specific markers, alkaline phosphatase and osteocalcin, was also reduced in RA-treated cultures. Normal human osteoblasts produced 31.0+/-4.8 pg IL-6 per ml in control cultures. Within 24 h, RA at all four concentrations reduced Il-6 production from normal human osteoblasts. The pharmacological concentration of 10(-5) M RA suppressed 90% of IL-6 production. The present study shows for the first time that RA profoundly inhibits IL-6 production in normal human osteoblasts within 24 h and in a dose-dependent manner. RA was shown previously to inhibit IL-6 production in several other normal and malignant human cell types. The associated decrease in osteoblast cell differentiation, alkaline phosphatase and osteocalcin production could result from the rapid RA-inhibition of IL-6 production. Thus, RA inhibition of IL-6 production in normal human osteoblasts may contribute to the bone abnormalities seen after systemic long-term retinoid therapy in some patients.

Alkaline Phosphatase↗
PubMed2000

Ceramides that mediate apoptosis reduce glucose uptake and transporter affinity for glucose in human leukaemic cell lines but not in neutrophils.

We have demonstrated that CD95-induced apoptosis in a human leukaemic T-cell line resulted in loss of glucose transporter function (Berridge et al. 1996). To determine whether ceramide, a mediator of CD95 and tumour necrosis factor-alpha-induced apoptosis, has similar effects on glucose transport, the human leukaemic cell lines, Jurkat and U937, and human peripheral blood neutrophils were treated with ceramide or sphingomyelinase and the effects on glucose transport determined by measuring [3H]-2-deoxyglucose uptake. We show that in U937 and Jurkat cells, the cell permeable ceramides, C2 (N-acetylsphingosine) and C6 (N-hexanoylsphingosine) inhibit glucose uptake within minutes of initiating ceramide treatment, 60-70% inhibition being observed within 2 hr. Loss of glucose transport correlated with loss of proliferative response, but metabolic activity as measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction, was affected to a much lesser extent. With Jurkat and U937 cells, the inhibitory effects of ceramides on glucose transport were associated with reduced affinity of glucose transporters for glucose (Km). Similar effects were observed with sphingomyelinase. With human peripheral blood neutrophils, C2 and C6-ceramides inhibited glucose uptake by 70-80% within 30 min. without affecting transporter affinity for glucose, but the maximum velocity of uptake (Vmax) was reduced. These results show that acute regulation of glucose transport is an early effector mechanism of cell death induced by ceramides in human leukaemic cell lines and peripheral blood neutrophils. This is the first study which describes ceramide-induced early physiological/biochemical events leading to cell death in human cells.

Apoptosis↗
PubMed2000

Unintentional injury mortality and socio-economic development among 15-44-year-olds: in a health transition perspective.

Injury imposes one of the greatest health risks in terms of mortality and morbidity among 15-44-y-olds. There is evidence that socio-economic development (SED) is related to injury risk, but the findings are inconsistent. We aimed to study the magnitude, pattern and relative importance of unintentional injury mortality (UIM) in relation to SED in this age group. Cross-sectional data on UIM by age-sex specific groups were obtained for 54 countries from the World Health Statistics Annuals 1993-1995. The relationship between UIM and SED (measured in gross national product (GNP) per capita) was studied using two methods: (1) with regression analysis, and (2) by categorizing the data into four income-based country groups and then comparing the differences in their mean values. The results were: (1) UIM rates were inversely correlated with GNP per capita and the relationship became stronger with increasing age (r=-0.22 for both sexes in the 15-24-y-olds, r=-0.65 for males, r=-0.54 for females in the 35-44-y-olds); (2) there was an increase in UIM rates between low-income and lower-middle-income countries (LoMIC), but a decrease between LoMIC and upper middle-income (UpMIC), and finally also a significant decrease between UpMIC and high-income countries in most age-sex groups (ie P<0.005 for males, P<0.05 for females in the 35-44-y-olds). The highest rates of UIM were in LoMIC for all age-sex groups. Male rates were consistently higher than female in all age groups. In conclusion, SED was inversely related to UIM. There was an initial positive relation between GNP per capita and UIM, which became negative with increasing GNP per capita. We also found a health transition that had taken place in all country groups.

Accidents↗
PubMed2000

Diversion colitis in patients with myelopathy: clinical, endoscopic, and histopathological findings.

OBJECTIVE: One of the problems with a diverting colostomy, applied in patients with myelopathy for complications of the neuropathic large bowel, is diversion colitis. A clinical, endoscopic, and histological survey was conducted to describe the problem in these patients. METHODS: 19 patients with myelopathy who have had colostomies (68% of those available) participated in the survey. History of rectal discharge and perineal ulceration plus colonoscopic and biopsy observations were recorded. 20 patients with myelopathy who have not had colostomies, with clinically indicated colonoscopic examinations, were compared for skin breakdown and endoscopic appearance. RESULTS: 15 patients who had colostomies (79%) reported rectal discharge, and 9 (47%) sustained perineal ulceration, 2 being recurrent and refractory. None of the 20 patients who had not had colostomies had perineal ulceration (p = 0.04). Colonoscopy revealed mucosal erythema and friability in 18 patients (94%) with a predominance in the rectosigmoid colon. 1 of 20 without colostomy presented with this picture (p < 0.001). Mucosal biopsies of diverted colon revealed chronic inflammation in all patients, severe inflammation in 13 of 19 subjects at < or = 20 cm from the anus, and in 3 of 10 at > 20 cm (p = 0.06). No difference in the severity of inflammation with time, 0 to 2 years versus > 2 to 18 years post colostomy, could be demonstrated. CONCLUSIONS: Diversion colitis is a frequent, persistent, and sometimes problematic complication in patients with myelopathy who have also had colostomies.

Adult↗
PubMed2000

Mass spectrometric monitoring of albumin in uremia.

BACKGROUND: Advanced glycation end products (AGEs) are a novel class of uremic toxins. In plasma, they are present in proteins and also in low molecular mass peptides. AGE-modified peptides are thought to bind and modify plasma proteins. Monitoring of the consequent increase in molecular mass of serum albumin may be used in surveillance of the clinical management of uremia. METHODS: We investigated molecular mass changes of human serum albumin (HSA) glycated by glucose and methylglyoxal in vitro and of subjects with moderate renal impairment, end-stage renal disease (ESRD), ESRD on hemodialysis, and normal healthy controls by matrix-assisted laser desorption ionization mass spectrometry. RESULTS: Fatty acid-free HSA had a molecular mass of 66,446 +/- 114 D. Mean (+/-SD) molecular mass increases were HSA minimally glycated by glucose 399 +/- 88 D (N = 5, P < 0.001), HSA highly glycated by glucose 6780 +/- 122 D (N = 5, P < 0.001), HSA minimally glycated by methylglyoxal 73 +/- 121 D (N = 5, P > 0.05), and HSA without fatty acid removal 535 +/- 90 D (N = 5, P < 0.001). For HSA of human subjects, mean (+/- SD) molecular mass increases were normal healthy controls 243 +/- 97 D (N = 5), moderate renal impairment 350 +/- 83 D (P > 0.05 with respect to controls, N = 5), ESRD 498 +/- 128 (P < 0.02 with respect to controls, N = 3), and ESRD on hemodialysis 438 +/- 85 D (P < 0.02 with respect to controls, N = 5). The mean molecular mass of albumin of all groups was increased significantly with respect to that of fatty acid free albumin (P < 0.001). CONCLUSIONS: Only ESRD was associated with a significant increase in the molecular mass of HSA in vivo. Since this mass increase was very low and much lower than reported for AGE-modified peptides, it may reflect AGE formation on HSA by alpha-oxoaldehydes that accumulate in uremia, rather than modification of albumin by AGE-modified peptides. The molecular mass of HSA in vivo was indicative of a minimal and not a high extent of glycation.

Adult↗